violette gijsen - Academia.edu (original) (raw)

Papers by violette gijsen

Clinical and Translational Science, Sep 13, 2019

Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespre... more Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespread and rapidly growing use. In medicine, however, it remains a novel approach to reach out to patients. Yet, they have the potential for further improving current health care. Electronic platforms could support therapy adherence and communication between physicians and patients. The power of social media as well as other electronic devices can improve adherence as evidenced by the development of the app bant. Additionally, systemic analysis of social media content by Screenome can identify health events not always captured by regular health care. By better identifying these healthcare events we can improve our current healthcare system as we will be able to better tailor to the patients' needs. All these techniques are a valuable component of modern health care and will help us into the future of increasingly digital health care.

Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineu... more Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation. Eur. J. Clin. Pharmacol. 68, 259-266 (2012). 15. Wallemacq, P. et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit 31, 139-152 (2009). 16. Ferraris, J. R. et al. Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids.

Clinical and Translational Science, 2019

Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespre... more Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespread and rapidly growing use. In medicine, however, it remains a novel approach to reach out to patients. Yet, they have the potential for further improving current health care. Electronic platforms could support therapy adherence and communication between physicians and patients. The power of social media as well as other electronic devices can improve adherence as evidenced by the development of the app bant. Additionally, systemic analysis of social media content by Screenome can identify health events not always captured by regular health care. By better identifying these healthcare events we can improve our current healthcare system as we will be able to better tailor to the patients’ needs. All these techniques are a valuable component of modern health care and will help us into the future of increasingly digital health care.

Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineu... more Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation. Eur. J. Clin. Pharmacol. 68, 259-266 (2012). 15. Wallemacq, P. et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit 31, 139-152 (2009). 16. Ferraris, J. R. et al. Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids.

Annals of Transplantation, 2012

Critical Care Medicine, Apr 1, 2011

Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associat... more Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associated with acute liver failure (ALF) in patients with myopathies Design-retrospective analysis Setting-level III pediatric intensive care unit Patients-two pediatric patients with myopathies and acute liver failure Clinical Investigations-We determined acetaminophen protein adduct levels, in combination with a literature review and systematic evaluation of the cases, using the Roussel Uclaf Causality Assessment Method (RUCAM) for drug-induced liver injury (DILI) to assess causality between recommended acetaminophen dosing and acute liver failure in two children with myopathies. Main Results-The serum adduct levels were consistent with the values previously reported in children with acute liver injury following APAP overdose. We found four similar cases of ALF in pediatric and adult patients with myopathies following recommended APAP doses in the literature (n=3) and personal communication (n=1).The RUCAM suggested a probable relationship between APAP use at recommended doses and ALF in our myopathy patients. Conclusions-Our data suggest that some patients with myopathies receiving recommended doses of APAP may be at increased risk for the development of toxicity resulting in ALF. More studies are needed to corroborate these findings. In the meantime, we would advise physicians to be alert in these patients while taking APAP, especially when critically ill or postoperative.

Therapeutic Drug Monitoring, Apr 1, 2014

Background: Both age and CYP3A5 genotype are important determinants of tacrolimus disposition in ... more 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 CYP3A5expressing 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.

Canadian Journal of Cardiology, Sep 1, 2012

61.7%, p 0.0001). There were 298 deaths in the follow-up period, 190 of which occurred in the non... more 61.7%, p 0.0001). There were 298 deaths in the follow-up period, 190 of which occurred in the non-CR group. CR completion was associated with reduced mortality (HR 0.55, 95% CI 0.43, 0.70), reduced hospitalization (HR 0.70, 95%CI 0.59, 0.83), reduced cardiac hospitalizations, and reduced CHF-specific hospitalizations. Of the CR completers, 529 (81.3%) matched to non-completers. In the propensity matched subgroup, CR completion remained associated with decreased mortality, hospitalizations, cardiac hospitalizations, and CHF hospitalizations. CONCLUSION: Using a tightly controlled propensity matched analysis in a well characterized group of patients, we found that CR attendance is associated with reduced mortality and hospitalization in CHF patients. Therefore, contrary to more recent analyses, our results indicate CR is an integral component of care in the CHF population.

The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique, 2008

A recent study published from the University College London suggests that children of women who w... more A recent study published from the University College London suggests that children of women who were light drinkers during pregnancy demonstrate better cognitive outcome at three years of age when compared to children of abstinent women based on data from the UK Millennium Cohort Study. Unfortunately, methodological pitfalls and limited external validity of the results presented make conclusions very tenuous. This paper was widely quoted by the media, sometimes concluding that drinking is beneficial. At the present state of knowledge, the poor quality of this study may cause more damage than benefit, as demonstrated by the media response.

The Annals of pharmacotherapy, 2009

To describe a child who developed a skin reaction during gabapentin therapy and discuss how we ev... more To describe a child who developed a skin reaction during gabapentin therapy and discuss how we evaluated the probability of an adverse drug reaction. An 8-year-old boy with a neurodegenerative disease of unknown origin and an epilepsy disorder developed an urticarial rash and irritability 10 and 4 days, respectively, after the start of gabapentin 20 mg/kg 3 times a day for epilepsy control. Otherwise, the child was well; no changes in other medication or diet had recently been made. After gabapentin discontinuation and administration of one dose of methylprednisolone 10 mg/kg intravenously and diphenhydramine 1 mg/kg every 4 hours via gastric tube, the rash disappeared over 3 weeks. In contrast to other antiepileptic drugs, skin reactions to gabapentin are considered uncommon. In adults, reported prevalence of rash possibly related to gabapentin range from 1% to 10%. A postmarketing surveillance study reported gabapentin treatment failure as a consequence of rash in 0.4% of 3000 pat...

BMJ open, 2011

Approximately 25% of all babies in North America are delivered via Caesarean section (C-section).... more Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine, passes into breast milk, and may produce unwanted side effects in neonates; therefore, alternatives to opioids are being sought. Reiki is an ancient Japanese form of healing where practitioners transfer healing energy through light touch and positive healing intention. Although 1.2 million Americans use reiki to reduce pain or depression, there is a lack of strong evidence supporting its effectiveness. A recent systematic review showed existing studies to be of poor methodological quality, with the common limitation of lack of blinding. To overcome this issue, the authors used distant reiki to assess its effectiveness in reducing pain following an elective C-section. In this randomised, double-blinded study, women...

Pharmacogenomics, 2013

Background: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. We aimed to determine the relatio... more Background: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. We aimed to determine the relationship between the CYP3A4*22 polymorphism and combined CYP3A genotypes with tacrolimus disposition in pediatric heart transplant recipients. Methods: Sixty pediatric heart transplant recipients were included. Tacrolimus doses and trough concentrations were collected in the first 14 days post-transplantation. CYP3A phenotypes were defined as extensive (CYP3A5*1 + CYP3A4*1/*1 carriers), intermediate (CYP3A5*3/*3 + CYP3A4*1/*1 carriers) or poor (CYP3A5*3/*3 + CYP3A4*22 carriers) metabolizers. Results: CYP3A4*22 carriers needed 30% less tacrolimus (p = 0.016) to reach similar target concentrations compared with CYP3A4*1/*1 (n = 56) carriers. Poor CYP3A metabolizers required 17% (p = 0.023) less tacrolimus than intermediate and 48% less (p < 0.0001) than extensive metabolizers. Poor metabolizers showed 18% higher dose-adjusted concentrations than intermediate (p = 0.35) and 193% higher than...

The Journal of Heart and Lung Transplantation, 2012

The FDCM cohort was younger (pϭ0.0001) with less DM (pϽ0.0001) & renal dysfunction (pϭ0.0001). It... more The FDCM cohort was younger (pϭ0.0001) with less DM (pϽ0.0001) & renal dysfunction (pϭ0.0001). It was also associated with higher PRA (pϽ0.0001) & VAD use (pϭ0.012). FDCM dx increased by era (Table 1). Survival (3, 5 & 10y) was: FDCM (91, 84, 64%) & non-FDCM (88, 80, 55%) (Figure 1, log rank pϽ0.0004). FDCM unadjusted HR for all-cause mortality was 0.72 (CI 0.60-0.86, pϭ0.0002). Multivariate analysis yielded a HR of 0.75 (CI 0.62-0.90, pϽ0.0001). Conclusions: FDCM post-HT survival was significantly better & was associated with younger age & improved renal function, increased VAD use & higher PRA. Further study is needed as this may reflect selection bias as FDCM percentage is likely underestimated.

The Journal of Heart and Lung Transplantation, 2011

BACKGROUND-Tacrolimus is one of the commonly used immunosuppressive drugs for pediatric heart tra... more BACKGROUND-Tacrolimus is one of the commonly used immunosuppressive drugs for pediatric heart transplants. Large variation exists in pharmacokinetics during the direct posttransplant period, resulting in an increased risk of adverse events. Limited data are available on the interaction of age, CYP3A5 and ABCB1 genotype, and disease severity on the variation in disposition and outcome in pediatric heart transplant recipients. METHOD-We studied the relationship between age and CYP3A5 and ABCB1 genotype and the Pediatric Risk of Mortality (PRISM) score on tacrolimus dose (mg/kg), steady-state trough concentrations, and concentration/dose ratio, as well as rejection and renal function for 14 days after heart transplant in children. RESULTS-Tacrolimus was administered to 39 children (median age, 6.0 years) after transplant. A correlation was found between the age at the time of transplant and the tacrolimus dosing requirements (r s = −0.447, p = 0.004) and the concentration/dose ratio (r s = 0.351, p = 0.029). CYP3A5 expressors required median (interquartile range) higher doses of tacrolimus (0.14 [0.09] vs 0.06 [0.04] mg/kg/12 hours, p = 0.001), and had lower concentration/dose ratios (45.34 [44.54] vs 177.78 [145.38] ng/ml per mg/kg/12 hours, p < 0.0001). This relationship was not seen with the ABCB1 genotype. Age and CYP3A5 genotype predicted the tacrolimus dosing requirements as well as the concentration/dose ratio (R 2 = 0.351, p = 0.001 and R 2 = 0.521, p < 0.001). No relationship was found between any of the CYP3A5 or ABCB1 genotypes and the estimated glomerular filtration rate. CONCLUSION-Younger age and CYP3A5 expressor genotype were independently associated with higher dosing requirements and lower tacrolimus concentration/dose ratios.

The Journal of Alternative and Complementary Medicine, 2009

Purpose: 5-fluorouracil (5-FU), an effective chemotherapy drug, is commonly applied for colorecta... more Purpose: 5-fluorouracil (5-FU), an effective chemotherapy drug, is commonly applied for colorectal cancer treatment. Nevertheless, its toxicity to normal tissues and the development of tumor resistance are the main obstacles to successful cancer chemotherapy and hence, its clinical application is limited. The use of resveratrol can increase 5-FUinduced cytotoxicity and mitigate the unwanted adverse effects. This study aimed to review the potential therapeutic effects of resveratrol in combination with 5-FU against colorectal cancer. Methods: According to the PRISMA guideline, a comprehensive systematic search was carried out for the identification of relevant literature in four electronic databases of PubMed, Web of Science, Embase, and Scopus up to May 2021 using a pre-defined set of keywords in their titles and abstracts. We screened 282 studies in accordance with our inclusion and exclusion criteria. Thirteen articles were finally included in this systematic review. Results: The in vitro findings showed that proliferation inhibition of colorectal cancer cells in the groups treated by 5-FU was remarkably higher than the untreated groups and the co-administration of resveratrol remarkably increased cytotoxicity induced by 5-FU. The in vivo results demonstrated a decrease in tumor growth of mice treated by 5-FU than the untreated group and a dramatic decrease was observed following combined treatment of resveratrol and 5-FU. It was also found that 5-FU alone and combined with resveratrol could regulate the cell cycle profile of colorectal cancer cells. Moreover, this chemotherapeutic agent induced the biochemical and histopathological changes in the cancerous cells/tissues and these alterations were synergized by resveratrol co-administration (for most of the cases), except for the inflammatory mediators.

Critical Care Medicine, 2011

Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associat... more Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associated with acute liver failure (ALF) in patients with myopathies Design-retrospective analysis Setting-level III pediatric intensive care unit Patients-two pediatric patients with myopathies and acute liver failure Clinical Investigations-We determined acetaminophen protein adduct levels, in combination with a literature review and systematic evaluation of the cases, using the Roussel Uclaf Causality Assessment Method (RUCAM) for drug-induced liver injury (DILI) to assess causality between recommended acetaminophen dosing and acute liver failure in two children with myopathies. Main Results-The serum adduct levels were consistent with the values previously reported in children with acute liver injury following APAP overdose. We found four similar cases of ALF in pediatric and adult patients with myopathies following recommended APAP doses in the literature (n=3) and personal communication (n=1).The RUCAM suggested a probable relationship between APAP use at recommended doses and ALF in our myopathy patients. Conclusions-Our data suggest that some patients with myopathies receiving recommended doses of APAP may be at increased risk for the development of toxicity resulting in ALF. More studies are needed to corroborate these findings. In the meantime, we would advise physicians to be alert in these patients while taking APAP, especially when critically ill or postoperative.

Annals of Pharmacotherapy, Feb 1, 2009

Canadian Journal of Cardiology, 2012

61.5 vs 63.8 years, pϽ0.0001) and more likely to be male (74.4 vs 61.7%, pϽ0.0001). There were 29... more 61.5 vs 63.8 years, pϽ0.0001) and more likely to be male (74.4 vs 61.7%, pϽ0.0001). There were 298 deaths in the follow-up period, 190 of which occurred in the non-CR group. CR completion was associated with reduced mortality (HR 0.55, 95% CI 0.43, 0.70), reduced hospitalization (HR 0.70, 95%CI 0.59, 0.83), reduced cardiac hospitalizations, and reduced CHF-specific hospitalizations. Of the CR completers, 529 (81.3%) matched to non-completers. In the propensity matched subgroup, CR completion remained associated with decreased mortality, hospitalizations, cardiac hospitalizations, and CHF hospitalizations. CONCLUSION: Using a tightly controlled propensity matched analysis in a well characterized group of patients, we found that CR attendance is associated with reduced mortality and hospitalization in CHF patients. Therefore, contrary to more recent analyses, our results indicate CR is an integral component of care in the CHF population.

Pediatric Transplantation, 2013

Renal dysfunction after non-renal transplantation in adult tacrolimus-treated transplant patients... more Renal dysfunction after non-renal transplantation in adult tacrolimus-treated transplant patients is well documented. Little is known about its prevalence in children. Age-related changes in both disposition and effect of tacrolimus as well as renal function may preclude extrapolation of adult data to children. To systematically review the literature on renal dysfunction in non-renal pediatric transplant recipients treated with tacrolimus. PubMed/Medline, Embase, and Google were searched from their inception until April 19, 2012, with the search terms "tacrolimus," "renal function," "transplantation," and "children." Eighteen of 385 retrieved papers were considered relevant. Twelve dealt with liver, four with heart transplant, one with heart and lung transplant, and one with intestinal recipients. Reported prevalences of mild and severe chronic kidney disease ranged from 0% to 39% and 0% to 71.4%, respectively, for liver, and from 22.7% to 40% and 6.8% to 46%, respectively, for heart and/or lung transplant recipients. Ranges remained wide after adjusting for follow-up time and disease severity. Possible explanations are inclusion bias and definitions used for renal dysfunction. A considerable proportion of pediatric non-renal transplant patients who receive tacrolimus-based immunosuppression, appear to suffer from chronic kidney disease. This conclusion warrants further research into the real risk, its risk factors, and individualization of immunosuppressant therapy.

Therapeutic Drug Monitoring, 2011

Background: Codeine, a common opiate prescribed for pain postcesarean section (c-section), is bio... more Background: Codeine, a common opiate prescribed for pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. Objective: The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section. Methods: Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated. Results: Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers. Conclusions: In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with pain response.

Clinical and Translational Science, Sep 13, 2019

Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespre... more Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespread and rapidly growing use. In medicine, however, it remains a novel approach to reach out to patients. Yet, they have the potential for further improving current health care. Electronic platforms could support therapy adherence and communication between physicians and patients. The power of social media as well as other electronic devices can improve adherence as evidenced by the development of the app bant. Additionally, systemic analysis of social media content by Screenome can identify health events not always captured by regular health care. By better identifying these healthcare events we can improve our current healthcare system as we will be able to better tailor to the patients' needs. All these techniques are a valuable component of modern health care and will help us into the future of increasingly digital health care.

Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineu... more Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation. Eur. J. Clin. Pharmacol. 68, 259-266 (2012). 15. Wallemacq, P. et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit 31, 139-152 (2009). 16. Ferraris, J. R. et al. Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids.

Clinical and Translational Science, 2019

Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespre... more Electronic communication is becoming increasingly popular worldwide, as evidenced by its widespread and rapidly growing use. In medicine, however, it remains a novel approach to reach out to patients. Yet, they have the potential for further improving current health care. Electronic platforms could support therapy adherence and communication between physicians and patients. The power of social media as well as other electronic devices can improve adherence as evidenced by the development of the app bant. Additionally, systemic analysis of social media content by Screenome can identify health events not always captured by regular health care. By better identifying these healthcare events we can improve our current healthcare system as we will be able to better tailor to the patients’ needs. All these techniques are a valuable component of modern health care and will help us into the future of increasingly digital health care.

Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineu... more Yano, I. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation. Eur. J. Clin. Pharmacol. 68, 259-266 (2012). 15. Wallemacq, P. et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit 31, 139-152 (2009). 16. Ferraris, J. R. et al. Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids.

Annals of Transplantation, 2012

Critical Care Medicine, Apr 1, 2011

Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associat... more Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associated with acute liver failure (ALF) in patients with myopathies Design-retrospective analysis Setting-level III pediatric intensive care unit Patients-two pediatric patients with myopathies and acute liver failure Clinical Investigations-We determined acetaminophen protein adduct levels, in combination with a literature review and systematic evaluation of the cases, using the Roussel Uclaf Causality Assessment Method (RUCAM) for drug-induced liver injury (DILI) to assess causality between recommended acetaminophen dosing and acute liver failure in two children with myopathies. Main Results-The serum adduct levels were consistent with the values previously reported in children with acute liver injury following APAP overdose. We found four similar cases of ALF in pediatric and adult patients with myopathies following recommended APAP doses in the literature (n=3) and personal communication (n=1).The RUCAM suggested a probable relationship between APAP use at recommended doses and ALF in our myopathy patients. Conclusions-Our data suggest that some patients with myopathies receiving recommended doses of APAP may be at increased risk for the development of toxicity resulting in ALF. More studies are needed to corroborate these findings. In the meantime, we would advise physicians to be alert in these patients while taking APAP, especially when critically ill or postoperative.

Therapeutic Drug Monitoring, Apr 1, 2014

Background: Both age and CYP3A5 genotype are important determinants of tacrolimus disposition in ... more 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 CYP3A5expressing 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.

Canadian Journal of Cardiology, Sep 1, 2012

61.7%, p 0.0001). There were 298 deaths in the follow-up period, 190 of which occurred in the non... more 61.7%, p 0.0001). There were 298 deaths in the follow-up period, 190 of which occurred in the non-CR group. CR completion was associated with reduced mortality (HR 0.55, 95% CI 0.43, 0.70), reduced hospitalization (HR 0.70, 95%CI 0.59, 0.83), reduced cardiac hospitalizations, and reduced CHF-specific hospitalizations. Of the CR completers, 529 (81.3%) matched to non-completers. In the propensity matched subgroup, CR completion remained associated with decreased mortality, hospitalizations, cardiac hospitalizations, and CHF hospitalizations. CONCLUSION: Using a tightly controlled propensity matched analysis in a well characterized group of patients, we found that CR attendance is associated with reduced mortality and hospitalization in CHF patients. Therefore, contrary to more recent analyses, our results indicate CR is an integral component of care in the CHF population.

The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique, 2008

A recent study published from the University College London suggests that children of women who w... more A recent study published from the University College London suggests that children of women who were light drinkers during pregnancy demonstrate better cognitive outcome at three years of age when compared to children of abstinent women based on data from the UK Millennium Cohort Study. Unfortunately, methodological pitfalls and limited external validity of the results presented make conclusions very tenuous. This paper was widely quoted by the media, sometimes concluding that drinking is beneficial. At the present state of knowledge, the poor quality of this study may cause more damage than benefit, as demonstrated by the media response.

The Annals of pharmacotherapy, 2009

To describe a child who developed a skin reaction during gabapentin therapy and discuss how we ev... more To describe a child who developed a skin reaction during gabapentin therapy and discuss how we evaluated the probability of an adverse drug reaction. An 8-year-old boy with a neurodegenerative disease of unknown origin and an epilepsy disorder developed an urticarial rash and irritability 10 and 4 days, respectively, after the start of gabapentin 20 mg/kg 3 times a day for epilepsy control. Otherwise, the child was well; no changes in other medication or diet had recently been made. After gabapentin discontinuation and administration of one dose of methylprednisolone 10 mg/kg intravenously and diphenhydramine 1 mg/kg every 4 hours via gastric tube, the rash disappeared over 3 weeks. In contrast to other antiepileptic drugs, skin reactions to gabapentin are considered uncommon. In adults, reported prevalence of rash possibly related to gabapentin range from 1% to 10%. A postmarketing surveillance study reported gabapentin treatment failure as a consequence of rash in 0.4% of 3000 pat...

BMJ open, 2011

Approximately 25% of all babies in North America are delivered via Caesarean section (C-section).... more Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine, passes into breast milk, and may produce unwanted side effects in neonates; therefore, alternatives to opioids are being sought. Reiki is an ancient Japanese form of healing where practitioners transfer healing energy through light touch and positive healing intention. Although 1.2 million Americans use reiki to reduce pain or depression, there is a lack of strong evidence supporting its effectiveness. A recent systematic review showed existing studies to be of poor methodological quality, with the common limitation of lack of blinding. To overcome this issue, the authors used distant reiki to assess its effectiveness in reducing pain following an elective C-section. In this randomised, double-blinded study, women...

Pharmacogenomics, 2013

Background: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. We aimed to determine the relatio... more Background: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. We aimed to determine the relationship between the CYP3A4*22 polymorphism and combined CYP3A genotypes with tacrolimus disposition in pediatric heart transplant recipients. Methods: Sixty pediatric heart transplant recipients were included. Tacrolimus doses and trough concentrations were collected in the first 14 days post-transplantation. CYP3A phenotypes were defined as extensive (CYP3A5*1 + CYP3A4*1/*1 carriers), intermediate (CYP3A5*3/*3 + CYP3A4*1/*1 carriers) or poor (CYP3A5*3/*3 + CYP3A4*22 carriers) metabolizers. Results: CYP3A4*22 carriers needed 30% less tacrolimus (p = 0.016) to reach similar target concentrations compared with CYP3A4*1/*1 (n = 56) carriers. Poor CYP3A metabolizers required 17% (p = 0.023) less tacrolimus than intermediate and 48% less (p < 0.0001) than extensive metabolizers. Poor metabolizers showed 18% higher dose-adjusted concentrations than intermediate (p = 0.35) and 193% higher than...

The Journal of Heart and Lung Transplantation, 2012

The FDCM cohort was younger (pϭ0.0001) with less DM (pϽ0.0001) & renal dysfunction (pϭ0.0001). It... more The FDCM cohort was younger (pϭ0.0001) with less DM (pϽ0.0001) & renal dysfunction (pϭ0.0001). It was also associated with higher PRA (pϽ0.0001) & VAD use (pϭ0.012). FDCM dx increased by era (Table 1). Survival (3, 5 & 10y) was: FDCM (91, 84, 64%) & non-FDCM (88, 80, 55%) (Figure 1, log rank pϽ0.0004). FDCM unadjusted HR for all-cause mortality was 0.72 (CI 0.60-0.86, pϭ0.0002). Multivariate analysis yielded a HR of 0.75 (CI 0.62-0.90, pϽ0.0001). Conclusions: FDCM post-HT survival was significantly better & was associated with younger age & improved renal function, increased VAD use & higher PRA. Further study is needed as this may reflect selection bias as FDCM percentage is likely underestimated.

The Journal of Heart and Lung Transplantation, 2011

BACKGROUND-Tacrolimus is one of the commonly used immunosuppressive drugs for pediatric heart tra... more BACKGROUND-Tacrolimus is one of the commonly used immunosuppressive drugs for pediatric heart transplants. Large variation exists in pharmacokinetics during the direct posttransplant period, resulting in an increased risk of adverse events. Limited data are available on the interaction of age, CYP3A5 and ABCB1 genotype, and disease severity on the variation in disposition and outcome in pediatric heart transplant recipients. METHOD-We studied the relationship between age and CYP3A5 and ABCB1 genotype and the Pediatric Risk of Mortality (PRISM) score on tacrolimus dose (mg/kg), steady-state trough concentrations, and concentration/dose ratio, as well as rejection and renal function for 14 days after heart transplant in children. RESULTS-Tacrolimus was administered to 39 children (median age, 6.0 years) after transplant. A correlation was found between the age at the time of transplant and the tacrolimus dosing requirements (r s = −0.447, p = 0.004) and the concentration/dose ratio (r s = 0.351, p = 0.029). CYP3A5 expressors required median (interquartile range) higher doses of tacrolimus (0.14 [0.09] vs 0.06 [0.04] mg/kg/12 hours, p = 0.001), and had lower concentration/dose ratios (45.34 [44.54] vs 177.78 [145.38] ng/ml per mg/kg/12 hours, p < 0.0001). This relationship was not seen with the ABCB1 genotype. Age and CYP3A5 genotype predicted the tacrolimus dosing requirements as well as the concentration/dose ratio (R 2 = 0.351, p = 0.001 and R 2 = 0.521, p < 0.001). No relationship was found between any of the CYP3A5 or ABCB1 genotypes and the estimated glomerular filtration rate. CONCLUSION-Younger age and CYP3A5 expressor genotype were independently associated with higher dosing requirements and lower tacrolimus concentration/dose ratios.

The Journal of Alternative and Complementary Medicine, 2009

Purpose: 5-fluorouracil (5-FU), an effective chemotherapy drug, is commonly applied for colorecta... more Purpose: 5-fluorouracil (5-FU), an effective chemotherapy drug, is commonly applied for colorectal cancer treatment. Nevertheless, its toxicity to normal tissues and the development of tumor resistance are the main obstacles to successful cancer chemotherapy and hence, its clinical application is limited. The use of resveratrol can increase 5-FUinduced cytotoxicity and mitigate the unwanted adverse effects. This study aimed to review the potential therapeutic effects of resveratrol in combination with 5-FU against colorectal cancer. Methods: According to the PRISMA guideline, a comprehensive systematic search was carried out for the identification of relevant literature in four electronic databases of PubMed, Web of Science, Embase, and Scopus up to May 2021 using a pre-defined set of keywords in their titles and abstracts. We screened 282 studies in accordance with our inclusion and exclusion criteria. Thirteen articles were finally included in this systematic review. Results: The in vitro findings showed that proliferation inhibition of colorectal cancer cells in the groups treated by 5-FU was remarkably higher than the untreated groups and the co-administration of resveratrol remarkably increased cytotoxicity induced by 5-FU. The in vivo results demonstrated a decrease in tumor growth of mice treated by 5-FU than the untreated group and a dramatic decrease was observed following combined treatment of resveratrol and 5-FU. It was also found that 5-FU alone and combined with resveratrol could regulate the cell cycle profile of colorectal cancer cells. Moreover, this chemotherapeutic agent induced the biochemical and histopathological changes in the cancerous cells/tissues and these alterations were synergized by resveratrol co-administration (for most of the cases), except for the inflammatory mediators.

Critical Care Medicine, 2011

Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associat... more Objective-To determine the likelihood that recommended doses of acetaminophen (APAP) are associated with acute liver failure (ALF) in patients with myopathies Design-retrospective analysis Setting-level III pediatric intensive care unit Patients-two pediatric patients with myopathies and acute liver failure Clinical Investigations-We determined acetaminophen protein adduct levels, in combination with a literature review and systematic evaluation of the cases, using the Roussel Uclaf Causality Assessment Method (RUCAM) for drug-induced liver injury (DILI) to assess causality between recommended acetaminophen dosing and acute liver failure in two children with myopathies. Main Results-The serum adduct levels were consistent with the values previously reported in children with acute liver injury following APAP overdose. We found four similar cases of ALF in pediatric and adult patients with myopathies following recommended APAP doses in the literature (n=3) and personal communication (n=1).The RUCAM suggested a probable relationship between APAP use at recommended doses and ALF in our myopathy patients. Conclusions-Our data suggest that some patients with myopathies receiving recommended doses of APAP may be at increased risk for the development of toxicity resulting in ALF. More studies are needed to corroborate these findings. In the meantime, we would advise physicians to be alert in these patients while taking APAP, especially when critically ill or postoperative.

Annals of Pharmacotherapy, Feb 1, 2009

Canadian Journal of Cardiology, 2012

61.5 vs 63.8 years, pϽ0.0001) and more likely to be male (74.4 vs 61.7%, pϽ0.0001). There were 29... more 61.5 vs 63.8 years, pϽ0.0001) and more likely to be male (74.4 vs 61.7%, pϽ0.0001). There were 298 deaths in the follow-up period, 190 of which occurred in the non-CR group. CR completion was associated with reduced mortality (HR 0.55, 95% CI 0.43, 0.70), reduced hospitalization (HR 0.70, 95%CI 0.59, 0.83), reduced cardiac hospitalizations, and reduced CHF-specific hospitalizations. Of the CR completers, 529 (81.3%) matched to non-completers. In the propensity matched subgroup, CR completion remained associated with decreased mortality, hospitalizations, cardiac hospitalizations, and CHF hospitalizations. CONCLUSION: Using a tightly controlled propensity matched analysis in a well characterized group of patients, we found that CR attendance is associated with reduced mortality and hospitalization in CHF patients. Therefore, contrary to more recent analyses, our results indicate CR is an integral component of care in the CHF population.

Pediatric Transplantation, 2013

Renal dysfunction after non-renal transplantation in adult tacrolimus-treated transplant patients... more Renal dysfunction after non-renal transplantation in adult tacrolimus-treated transplant patients is well documented. Little is known about its prevalence in children. Age-related changes in both disposition and effect of tacrolimus as well as renal function may preclude extrapolation of adult data to children. To systematically review the literature on renal dysfunction in non-renal pediatric transplant recipients treated with tacrolimus. PubMed/Medline, Embase, and Google were searched from their inception until April 19, 2012, with the search terms "tacrolimus," "renal function," "transplantation," and "children." Eighteen of 385 retrieved papers were considered relevant. Twelve dealt with liver, four with heart transplant, one with heart and lung transplant, and one with intestinal recipients. Reported prevalences of mild and severe chronic kidney disease ranged from 0% to 39% and 0% to 71.4%, respectively, for liver, and from 22.7% to 40% and 6.8% to 46%, respectively, for heart and/or lung transplant recipients. Ranges remained wide after adjusting for follow-up time and disease severity. Possible explanations are inclusion bias and definitions used for renal dysfunction. A considerable proportion of pediatric non-renal transplant patients who receive tacrolimus-based immunosuppression, appear to suffer from chronic kidney disease. This conclusion warrants further research into the real risk, its risk factors, and individualization of immunosuppressant therapy.

Therapeutic Drug Monitoring, 2011

Background: Codeine, a common opiate prescribed for pain postcesarean section (c-section), is bio... more Background: Codeine, a common opiate prescribed for pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. Objective: The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section. Methods: Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated. Results: Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers. Conclusions: In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with pain response.