Tom Leibson

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.

Background Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy. Methods and Findings Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown. Conclusion This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.

Informed Consent in Pediatric Research

Pediatric drug research is gradually becoming more and more accepted as the norm for assessing whether a drug is safe and efficacious for infants and children. The process of informed consent and assent for these trials presents a major challenge. The aim of this review is to map historical, ethical and legal aspects relevant to the challenges of informed consent in the setting of pediatric drug research. The impact of age, level of maturity and life circumstances on the process of obtaining informed consent as well as the relations between consent and assent are discussed. There appears to be a lack of regulatory clarity in the area of pediatric clinical trials; while numerous statements have been made regarding children’s rights to autonomy and their ability to care for themselves and for younger ones, the ever changing status of adolescence is still difficult to translate to informed consent. This may delay scientific and clinical advancement for children who are at the very junction of being independent and not needing parental permission. Obtaining consent and assent for pediatric clinical trials is a delicate matter, as both parent and child need to agree to participate. The appropriate transfer of information to guardians and the children, especially concerning potential risks and benefits, is at the heart of informed consent, as it serves to protect both patient and physician. As many adults lack health literacy, one must ensure that guardians receive relevant information at a level and in forms they can understand regarding the trials their children are asked to participate in.

Reasons for substance use continuation and discontinuation during pregnancy: A qualitative study

BACKGROUND Substance use during pregnancy is a major public health concern, stemming from potential physical and psychosocial harms to both the mother and child. PURPOSE To understand womens experiences using substances during pregnancy and the reasons that women continue and/or discontinue using substances. METHODS Focus groups were conducted with women who attended an early intervention program for pregnant or parenting women with substance use issues. RESULTS Women identified that external and internal stressors, feelings of guilt and low-self efficacy, and a lack of understanding of the scientific and medical consequences of substance use contributed to their continued substance use. Conversely, women highlighted the importance of high self-efficacy and the quality of relationships when trying to make positive changes to their substance use during pregnancy. CONCLUSIONS Recommendations are proposed for easier access to and more comprehensive services. Healthcare professionals and service providers should offer non-judgmental care by building high-quality relationships with pregnant women with substance use issues, to increase these womens self-efficacy and empower them to discontinue substance use.

TDM Journal Club: Safety and Immunogenicity of Tetanus Diphtheria and Acellular Pertussis Immunization During Pregnancy.

INTRODUCTION In 2012, the Center for Disease Control and Prevention reported 48,277 cases of pertussis, which was increased from 18,719 in 2011. In late 2012, the Advisory Committee on Immunization Practices (ACIP) recommended that all pregnant women receive Tdap during the third trimester of every pregnancy to provide adequate transplacental antibody titers to protect infants from disease. However, the safety and efficacy of this practice needed to be established. For that end, Munoz et al conducted a randomized controlled trial looking at safety and immunogenicity of tetanus diphtheria and acellular pertussis immunization during pregnancy in mothers and infants. This article aims to critically appraise the article published by Munoz et al and to debate its ability to inform clinical practice.

Pediatric Wells syndrome (eosinophilic cellulitis) after vaccination: A case report and review of the literature.

A 4‐year‐old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with a recall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.

Drug and Chemical Contaminants in Breast Milk: Effects on Neurodevelopment of the Nursing Infant

Abstract Breast milk contains not only nutrients for the infant, but also various substances the mother is exposed to, including drugs and chemicals such as heavy metals, environmental pollutants, and nonmedicinal substances, which may compromise infant neurodevelopment. However, knowledge on the impact of these substances in milk on infant neurodevelopment is limited because most of these exposures continue throughout pregnancy and lactation, making it difficult to separate prenatal from postnatal effects. Moreover, concentrations of these substances in milk are low and breastfeeding has been repeatedly shown to be associated with tangible health benefits in the mother and infant, including favorable neurocognitive development. These factors pose significant challenges in study design and interpretation, but research efforts have been made, nonetheless. Overall, available evidence points toward the lack of major detrimental effects of these substances in milk on infant neurodevelopment.

Substance Use in Pregnancy Among Vulnerable Women Seeking Addiction and Parenting Support

Substance use during pregnancy is associated with obstetrical and fetal complications. Though use of some substances is discontinued during pregnancy, use of others persists. Our goal was to characterize substance-specific use and patterns of use throughout pregnancy among vulnerable women who attended an early intervention program for women with substance use issues. Through retrospective analyses of client records (1995–2016; N = 470), results indicated that the greatest number of women continued use of tobacco and cannabis for the duration of pregnancy (n = 232; 84.4% and n = 102; 60.0%, respectively), while the proportion of women continuing opioid use was relatively high (n = 33; 57.9%). Relapse rates were high for women who initially attempted to discontinue use of cocaine, crack cocaine, and heroin. Results can inform intervention and treatment by indicating which substances are more difficult to discontinue, as well as substances associated with high rates of relapse.

Hyperosmolar metabolic acidosis in burn patients exposed to glycol based topical antimicrobials—A systematic review

BACKGROUND The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents. METHODS Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy. RESULTS A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap. CONCLUSION This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner.