Prospective evaluation of pregnancy outcomes after gestational exposure to prazosin.

AIMS: Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. The aim of this study was to assess the fetal and pregnancy safety associated with prazosin exposures in early pregnancy. METHODS: Subjects were 11 patients who took prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between 1 January 2000 and 31 December 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires. RESULTS: It was found that 6/11 (54.5%) subjects did not report any adverse outcomes and experienced uneventful pregnancies. There were two miscarriages. Birthweights were within the normal range for the remaining nine pregnancies. Adverse events reported were consistent with background population expectation, including: one postpartum haemorrhage, one case of preeclampsia, one preterm birth, two NICU admissions, and two caesarean sections. CONCLUSIONS: For these 11 subjects, pregnancy outcomes after exposure to prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to prazosin while pregnant. Therefore, this study contributes valuable data towards monitoring safety of prazosin in pregnancy.

Peripartum hyperhemolysis prophylaxis and management in sickle cell disease: A case report and narrative review.

BACKGROUND: Sickle cell disease (SCD) is associated with hematologic complications including delayed hemolytic transfusion reactions (DHTRs) and pregnancy-related morbidity and mortality. Hyperhemolysis syndrome (HS) is the most severe form of DHTR in patients with SCD, in which both transfused and native red blood cells are destroyed. Further transfusions are avoided after a history of HS. Immunosuppressive agents can be used as prophylaxis against life-threatening hemolysis when transfusion is necessary. There is a paucity of evidence for the use of HS prophylaxis before transfusions, the continuation of hydroxyurea (HU) in lieu of chronic transfusion, and the use of erythropoiesis-stimulating agents (ESA) in pregnant SCD patients. CASE REPORT: We present a case of a pregnant patient with SCD and a previous history of HS. HS prophylaxis was given before transfusion with corticosteroids, intravenous immunoglobulin, and rituximab. In addition, HU was continued during pregnancy to control SCD, along with the use of concomitant ESA to maintain adequate hemoglobin levels and avoid transfusion. We describe a multidisciplinary approach to pregnancy and delivery management including tailored anesthetic and obstetric planning. CONCLUSION: This is the first published case of HS prophylaxis in a pregnant SCD patient, with good maternal and fetal outcomes after transfusion. HU and ESAs were able to control SCD and mitigate anemia in lieu of prophylactic transfusions during pregnancy. Further prospective studies are necessary to elucidate the ideal management of pregnant SCD patients with a history of HS or other contraindications to chronic transfusion.

Therapeutic drug monitoring in pregnancy.

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Palatability, adherence and prescribing patterns of antiretroviral drugs for children with human immunodeficiency virus infection in Canada.

PURPOSE: To assess the impact of perceived palatability of antiretroviral drugs on adherence to therapy of children infected by human immunodeficiency virus and on prescribing patterns by their caring physicians. DESIGN: Two arms--retrospective chart review and a cross-sectional survey. SETTING: Tertiary-care pediatric human immunodeficiency virus clinic during a 17-year period. PARTICIPANTS: Children with human immunodeficiency virus infection and physicians actively caring for children with human immunodeficiency virus infection in seven provinces in Canada were surveyed regarding their perception of the palatability of 8-liquid and 15 non-liquid antiretroviral medications and its effect on drug selection. MAIN OUTCOME MEASURE: Effect of taste preferences of antiretroviral drugs on adherence to treatment by infected children and on drug selection by their caring physicians. RESULTS: Forty of 119 children (34%) refused at least once to an antiretroviral medication. In 5%, treatment was discontinued because of poor palatability. Ritonavir was the least palatable drug (50% of children; p = 0.01). Ritonavir use (OR 4.80 [95%CI 1.34-17.20]) and male gender (OR 7.25 [95%CI 2.30-22.90]) were independent predictors of drug discontinuation because of poor taste. Physicians also perceived liquid ritonavir as the least palatable (p = 0.01) and the most likely to be discontinued (p = 0.01). However, they commonly prescribed it as first-line therapy (p = 0.06). CONCLUSIONS: A third of children infected with human immunodeficiency virus fail to adhere to their treatment because of poor drug taste. Physicians are aware of that, but this does not prevent them from selecting the least palatable drugs as first-line therapy.

Severe Generalized Bullous Fixed Drug Eruption Treated with Cyclosporine: A Case Report and Literature Review.

Generalized bullous fixed drug eruptions (GBFDEs) are rare in the paediatric population. We present the case of a 7-year-old girl with GBFDE believed to be secondary to oral ibuprofen, who experienced rapid resolution of lesions and cessation of blistering with a 3-week course of oral cyclosporine. To the best of our knowledge, this is the first report of a paediatric case of GBFDE treated with cyclosporine. In our report, we review published cases of GBFDE in children, and all adult cases managed with cyclosporine.

Adrenal Cushing Syndrome Diagnosed During Pregnancy: Successful Medical Management With Metyrapone.

Adrenal Cushing syndrome during pregnancy is rare, and there is limited information on the effect and safety of metyrapone treatment both for mother and fetus. We present a 24-year-old woman diagnosed with adrenal Cushing syndrome at the end of the second trimester. We elected treatment with metyrapone titrated to 250 mg 3 times daily, resulting in good clinical response and maternal serum and saliva cortisol levels in the upper half of the normal pregnancy range. A healthy male infant was born at 35 weeks' gestation, with no clinical signs of adrenal insufficiency, this despite a low cortisol of 5 nmol/L on the first day of life. We measured metyrapone in maternal and umbilical cord blood samples, demonstrating fetal venous metyrapone levels similar to maternal venous concentration, and a fetal arterial cord concentration at about 60% of the fetal venous cord concentration. This case demonstrates that salivary cortisol levels may be used to monitor the effect of metyrapone on adrenal Cushing syndrome during pregnancy. We show, for the first time in humans, that metyrapone does cross the placenta and may suppress fetal cortisol production without necessarily causing clinical signs of adrenal insufficiency.

Safety of 14C-UBT for diagnosis of Helicobacter pylori infection in pregnancy.

QUESTION: A 29-year-old woman had a carbon 14 urea breath test for diagnosis of Helicobacter pylori infection. At time of consultation, it had been 6 weeks since her last menstrual period. Four weeks after her last menstrual period, the results of a urine pregnancy test were negative. On that day, she received an ionizing radiation dose of 74 KBq (2 microCi) carbon 14 urea, followed by the breath test 30 minutes thereafter. Four days later, when the urine pregnancy test results turned positive, she was concerned about the possible effect of her exposure to ionizing radiation on the developing fetus. ANSWER: The amount of radiation used in these tests is extremely low-much lower than the amount a pregnant woman is absorbing through natural sources.

Elective tracheostomy in mechanically ventilated children in Canada.

OBJECTIVE: To determine the current practice and opinions of paediatric intensivists in Canada regarding tracheostomy in children with potentially reversible conditions which are anticipated to require prolonged mechanical ventilation. DESIGN AND SETTING: Self-administered survey among paediatric intensivists within paediatrics critical care units (PCCU) across Canada. MEASUREMENTS AND RESULTS: All 16 PCCUs participated in the survey with a response rate of 81% (63 physicians). In 14 of 16 centres one to five tracheostomies were performed during 2006. Two centres did not perform any tracheostomies. The overall rate of tracheostomy is less than 1.5%. Percutaneous technique is used in 3/16 (19%) of centres. Readiness to undertake tracheostomy during the first 21[Symbol: see text]days of illness is influenced by patient diagnosis; severe traumatic brain injury 66% vs. 42% in a 2-year-old with Guillain-Barré syndrome, 48% in a 9-year-old with Guillain-Barré syndrome, and 12% in a child with isolated ARDS. In a child with ARDS 25% of respondents would never consider tracheostomy. Age does not affect timing nor keenness for tracheostomy. The majority, 81%, believe that the risks associated with the procedure do not outweigh the potential benefits. Finally, 51% believe that tracheostomy is underutilized in children. CONCLUSIONS: Elective tracheostomy is rarely performed among ventilated children in Canada. However, 51% of physicians believe it is underutilized. The role of elective tracheostomy and the percutaneous technique in children requires further investigation.

MotherNature: establishing a Canadian research network for natural health products (NHPs) during pregnancy and lactation.

BACKGROUND: It has been estimated that between 7% and 55% of expectant mothers use herbal medicines or other types of natural health products (NHPs). Unfortunately, the safety and efficacy of NHPs during pregnancy and lactation is largely unknown. The Motherisk Program, at the Hospital for Sick Children, Toronto, Ontario, Canada, the is the major Canadian group to counsel and monitor outcomes of women using medications or NHPs, or of women exposed to chemicals, radiation or infection during pregnancy and lactation. OBJECTIVE: To create a network for research on NHPs during pregnancy and lactation by forming longstanding collaborations among Canadian medical and complementary and alternative medicine (CAM) practitioners and scientists. METHODOLOGY: MotherNature Network members participated in three 2-day workshops and three conference calls throughout the length of this study. Each member was responsible to lead discussions surrounding one theme and address the following: initiation; development; presentation; and synthesis of comments of all members on the designated theme. RESULTS: We prioritized areas in high need for future research and collaborative means to conduct such research. NHPs were prioritized for their importance for future study. Areas for the prospective collection of data on NHP use in pregnancy and lactation were identified. A research and business plan was developed for the long-term sustainability of the Network. CONCLUSIONS: The MotherNature Network is well-situated to create a new climate in Canada, where data are collected and interpreted on the effects and safety of NHPs during pregnancy and lactation.

Rural women and pharmacologic therapy: needs and issues in rural Canada.

INTRODUCTION: The needs and issues of rural women regarding pharmacologic information and therapy are rarely explored. We sought to explore the needs and issues of rural women in Canada regarding drug-related information and prescription and nonprescription pharmaceuticals. METHODS: We used the qualitative methodology of interpretive description. In-depth semistructured face-to-face interviews were conducted with 20 women aged 17-88 years who lived in rural southwestern Ontario. RESULTS: Although rural women accessed prescription medications, complementary and alternative medicine (CAM) was highly favoured, and alcohol and illicit drugs such as marijuana, crystal meth and cocaine were prevalent in rural communities. Factors that affected rural women's decisions about which medications to use included access to health care practitioners, costs of medications, experiences of family members and friends with prescribed and alternative medications, attitudes and approaches of health care providers and health store employees, and the women's own expectations and desires. Factors that affected the use of illicit drugs included availability, boredom, peer pressure and cultural norms. Rural factors that influenced access to drug information and use included presence or lack of confidential care, distance to resources, and presence, accessibility and acceptability of rural resources. CONCLUSION: Rural women use a variety of drug therapies and sources of information, and experience unique socioeconomic and environmental issues that affect access to appropriate drug-related information and therapies. Further research is needed to clarify and articulate pharmacologic needs, issues and solutions for women in diverse rural settings.

A needs assessment for obesity-related anticipatory guidance in the paediatric emergency department.

BACKGROUND: The prevalence of Canadian childhood obesity has been increasing, resulting in a call for improved prevention efforts and anticipatory guidance. OBJECTIVE: To evaluate interest in obesity-related anticipatory guidance in a paediatric emergency department. METHODS: Between September 2005 and September 2006, parents or patients older than 14 years of age were approached at the emergency department of the Children's Hospital (London, Ontario) to complete a survey. The survey compiled demographic data and asked questions regarding self-perceived weight status, use of dieting and/or exercise for weight loss, desire for nutrition and/or exercise information, and interest in receiving anticipatory guidance related to obesity. RESULTS: Two hundred people completed the survey; the vast majority (92%) of respondents were parents. The mean (+/- SD) age of the children was 12.6+/-3.9 years. Forty-one per cent of the respondents indicated an interest in further information on obesity (95% CI 34% to 48%). Fifty-two per cent of respondents considered themselves overweight or obese (95% CI 45% to 59%), and 52% reported someone in their family who was dieting, exercising or both to lose weight. Parents who stated that their children considered themselves to be overweight or obese were significantly less interested in anticipatory guidance than parents who did not believe that their children considered themselves to be overweight or obese (67% versus 90%, respectively; P=0.009). DISCUSSION: Many patients in the paediatric emergency department desire information on nutrition and exercise. Further research into risk-stratified targeting of patients and parents are needed to help identify good candidates for anticipatory guidance.

Current issues in pediatric medication adherence.

With the recent emphasis on investigating the efficacy of medication in children, it is also important to assess what determines whether pediatric patients do or do not take their medication. In general, children are no better at adhering to drug therapy than older individuals. Dealing with medication nonadherence is essential given its association with a failure to achieve the desired treatment goal. In addition to the many factors that influence adherence in adults, there are some unique challenges faced in the pediatric age group including the role of family (and its dysfunction), the changes of adolescence, and the lack of appropriate drug formulations. Intervention strategies to improve adherence include behavioral and educational strategies. Although there is no consensus as to what is the best approach to promote adherence with therapy, attention should be given to determining what barriers exist and trying to overcome them by involving children and their parents in the treatment planning process. If possible, the medication regimen, taking into account the frequency and timing of administration, should be tailored to the child and family's lifestyle and daily routine. Consideration should be given to the palatability and formulations of medications prescribed for young children. The use of simplified regimens of better tasting medications and age-appropriate delivery mechanisms may enhance the ability of pediatric patients to adhere to their drug therapy.

Naproxen versus acetaminophen for therapy of soft tissue injuries to the ankle in children.

BACKGROUND: Musculoskeletal (MSK) ankle injuries cause significant morbidity in ambulatory pediatric populations. No optimal pharmacotherapy is available. OBJECTIVE: To conduct a randomized, double-blind trial to compare 2 drug therapies for soft tissue injury of the ankle. METHODS: Patients (N = 77, aged 8-14 y, 61% male) with ankle injuries presenting to a regional pediatric emergency department were assigned to receive either acetaminophen (15 mg/kg 4 times a day) or naproxen (5 mg/kg 4 times a day) in a double-blind fashion on a routine basis for a 5 day period. On days 0 and 7, patients rated their degree of disability and pain on weight bearing using a 10 cm visual analog scale developed for this study. In addition, they were examined by a physician who rated pain, tenderness on palpation, and swelling using a 4 point scale. There were 3 follow-up telephone calls on days 3, 14, and 21. Adherence was evaluated by self-report and pill count. RESULTS: Both the acetaminophen and naproxen groups had significant improvement in degree of disability and pain from day 0 to day 7. There was no statistically significant difference in outcome between the 2 groups by patient self-evaluation or physician assessment. There also was no significant difference in adverse event rates between the 2 groups, and the majority of patients in both groups felt that the medication was helpful. CONCLUSIONS: No significant difference in efficacy of pain control or improvement of disability between the naproxen and acetaminophen groups suggests no preferential advantage for naproxen over acetaminophen for MSK injuries when given on a regular basis, with concurrent supportive treatment. Possible differential benefit from intermittent therapy needs to be evaluated among children with ankle injury.

Screening for iron deficiency anemia in at risk children in the pediatric emergency department: a survey of Canadian pediatric emergency department physicians.

OBJECTIVE: To determine the attitudes and reported practices of physicians regarding screening for iron deficiency anemia in at-risk children in pediatric emergency departments (PEDs) across Canada. METHODS: A standardized survey was mailed to 183 PED physicians at 10 tertiary care PED across Canada. The practices and attitudes regarding screening for iron deficiency anemia were collected via a questionnaire consisting of single select closed-ended items and items which required ranking in order of importance. RESULTS: Sixty-one percent (111/183) of physicians responded to the survey. Ninety-six percent of respondents do not routinely screen for iron deficiency anemia. One third of respondents believed that screening for iron deficiency anemia in the PED is possible. The remaining stated lack of time, difficulty with follow-up, it not being an emergent issue and cost as prohibitive factors. One third of participants stated that 21% to 40% of the pediatric patients seen in their PED did not have a primary care physician. The main considerations in deciding on whom to perform venipuncture were based on dietary history and physical examination with a history of consumption of milk greater than 24 ounces per day (94%) and conjunctival or skin pallor (97%, 94%, respectively) selected as the most important items. CONCLUSION: The results of this study indicate that Canadian PED physicians are not routinely screening for iron deficiency anemia, although they demonstrate knowledge of the risk factors for iron deficiency anemia and recognize the importance of diagnosis and treatment to prevent long-term morbidity.

Young children's perceptions of physicians wearing standard precautions versus customary attire.

OBJECTIVE: The aim of the study was to determine if young children have a preference regarding whether physicians wear standard precautions attire. METHODS: One hundred ninety-seven children, aged 4 to 8 years, and their parents were recruited from the pediatric emergency department of a tertiary care center. Two sets of 4 photographs-the same man in formal attire, a white coat, greens, and severe acute respiratory syndrome (SARS) standard precautions attire, and the same woman in formal attire, a white coat, greens, and SARS standard precautions attire-were shown to the children and their caregiver. Both were asked which physician's attire he or she liked the most and which he or she liked the least. Parents filled out a questionnaire regarding their experiences in the pediatric emergency department during the SARS epidemic. RESULTS: The children selected the physician in SARS standard precautions attire as most liked 17.5% of the time and least liked 53.3% of the time. The parents selected the physician in SARS standard precautions attire as most liked 0% of the time and least liked 94.8% of the time. CONCLUSIONS: Physicians wearing standard precautions attire while working in the pediatric emergency department need to be aware that this attire may negatively impact their relationship with pediatric patients 4 to 8 years of age.

Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update.

During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in the folate metabolic cycle, those exposed to medications with antifolate effects, smokers, diabetics, and the obese may benefit from higher doses of folic acid daily during the first trimester.

Sleep-promoting medications in children: physician prescribing habits in Southwestern Ontario, Canada.

BACKGROUND: Research indicates that physicians may frequently use pharmacotherapy to treat pediatric insomnia despite minimal safety data and very limited indications. Canadian data on the subject are lacking. This study aimed to determine physicians' views on and prescribing habits for sleep-promoting over-the-counter medication (OTCM) and prescription (RXM) medications for children. METHODS: A modified 26-item version of the 'Pediatric Sleep Medication Survey', originally developed by Judith Owens and colleagues, was sent to 100 pediatricians and a random sample of 421 family physicians in Southwestern Ontario, Canada. RESULTS: A total of 67 returned surveys were sufficiently complete for analysis. Sixty-one respondents indicated their specialty (28 pediatricians, 33 family physicians). In a typical 6-month period, 89% and 66% of respondents have recommended OTCM and RXM, respectively, for children with sleep problems. Only 20% have received any formal training on pediatric sleep disorders. The most common circumstances and sleep problems for which OTCM or RXM were recommended were mood disorders, developmental delay and attention deficit hyperactivity disorder (ADHD) (56, 40, and 39%, respectively), and insomnia, bedtime struggles/delayed sleep onset and circadian rhythm disorders (52, 48, and 28%, respectively). A total of 30% recommended OTCM or RXM to otherwise healthy children with sleep problems. Melatonin (73%), OTC antihistamines (41%), antidepressants (37%), and benzodiazepines (29%) were the most commonly recommended OTCM and RXM, respectively. CONCLUSIONS: Respondents in our sample frequently use pharmacotherapy to treat pediatric sleep problems; few have received any training in this area. Our findings indicate the need for evidence-based guidelines and regular physician training in the management of pediatric sleep disorders.

Paediatrician human resource planning in Canada: A 10-year follow-up.

BACKGROUND: Paediatrician human resource planning in Canada is currently a major concern. The optimal mix of physicians by type of practice and geographical distribution also remains controversial for many groups of physicians. OBJECTIVE: To compare 10-year trends (1987 to 1997) in paediatric practice with respect to age, sex and percentage of paediatricians practicing tertiary care. METHODS: Information on the demographics and practice patterns of Canadian paediatricians obtained from national surveys conducted in 1987 and 1997 was examined. RESULTS: In the 1987 survey, 1960 paediatricians were mailed a questionnaire, and 1352 questionnaires were returned (response rate of 69%). In the 1997 survey, 1706 of 2337 paediatricians returned the completed questionnaire (response rate of 73%). In 1987, 26.2% of paediatricians were women compared with 38.5% in 1997 (P<0.0001). When men and women were combined, 14.5% of paediatricians were in the 25- to 34-year age bracket in 1987, compared with only 9.7% in 1997 (P=0.0002). In 1987, 37.7% of paediatricians reported practicing tertiary care versus 38.7% in 1997 (P=0.61). In addition, tertiary care paediatricians have become more centralized in communities with more than 100,000 people. CONCLUSIONS: The results confirm that the paediatric workforce is aging, located primarily in large urban areas and shifting toward more women. Shortages of paediatricians, especially in remote and rural areas, continue to be a major concern and show no signs of improvement. The potential impact of these changes on delivery and quality of child-care services in the future needs to be assessed.

Ethics of studies of drugs in pregnancy.

Pregnant women with illness require efficacious and safe drug therapy during pregnancy; however, their treatment is often hindered by a lack of information regarding the use of medications during pregnancy. Ethical challenges are encountered in conducting drug trials in pregnant women, who are often excluded from participation due to fear of harm to the fetus. However, as the health of the fetus is ultimately affected by that of the pregnant woman, inclusion of pregnant women in studies of medications that they may require for their own benefit may also benefit the unborn child. The principle of autonomy argues for the pregnant woman being able to make an informed choice to take part in a clinical trial, and the principle of justice dictates that she not be denied the benefits of drug research.