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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 163 records · Page 9Linked to original sources

Treatment of epilepsy in pregnancy.

Pregnant women with epilepsy constitute 0.5% of all pregnancies. Proper seizure control is the primary goal in treating women with epilepsy. The commonly used anticonvulsants are established human teratogens. Factors such as epilepsy, anticonvulsant-induced teratogenicity, patient's genetic predisposition and the severity of convulsive disorder may attribute to adverse pregnancy outcome for the children of women with epilepsy. Anticonvulsant interaction with folic acid and phytomenadione (vitamin K) metabolism may lead to an increased risk for neural tube defect and early neonatal bleeding. Psychological, hormonal and pharmacokinetic changes in pregnancy may escalate seizure activity. Preconceptional counselling should include patient education to ensure a clear understanding of risks of uncontrolled seizures and possible teratogenicity of anticonvulsants. Genetic counselling should be performed if both parents have epilepsy or the disease is inherited. Seizure control should be achieved at least 6 months prior to conception and, if clinically possible, by the lowest effective dose of a single anticonvulsant according to the type of epilepsy. The new anticonvulsants are not recommended in pregnancy and require further research to prove their safety in humans. Folic acid 5 mg/day should be administered 3 months before conception and during the first trimester to prevent folic acid deficiency-induced malformations. Antenatal management should include assessment of patients for anticonvulsant-associated birth defects through detailed ultrasound examination and levels of maternal serum alpha-fetoproteins. Therapeutic drug monitoring should be performed monthly, or as clinically indicated. If phenobarbital, carbamazepine or phenytoin is administered, maternal phytomenadione supplementation should begin 4 weeks before the expected date of delivery. In order to prevent convulsions during labour, proper seizure control should be achieved during the third trimester. Benzodiazepines or phenytoin are found to be effective for seizure cessation during labour and delivery. Phytomenadione should be administered immediately after birth to the newborn. The neonate should be assessed carefully for epilepsy and anticonvulsant-associated dysmorphology. Advising the patient on postpartum management regarding contraception and breast-feeding will help maximise the best possible outcome for the newborn and mother. With proper preconceptional, antenatal and postpartum management up to 95% of these pregnancies have been reported to have favourable outcomes.

Abnormalities, Drug-Induced↗

Young women taking isotretinoin still conceive. Role of physicians in preventing disaster.

QUESTION: One of my adolescent patients was prescribed isotretinoin for severe acne by a dermatologist. I was shocked to discover she does not use any means of contraception. The dermatologist insists he told her about the need for contraception. How can we do better? ANSWER: Clearly this dermatologist, like many of his colleagues, does not comply with the Pregnancy Prevention Program. Until physicians become more aware of this program, babies will continue to be born with embryopathy due to isotretinoin.

Abnormalities, Drug-Induced↗

Erythema infectiosum (Fifth disease) and pregnancy.

QUESTION: One of my patients is currently 14 weeks pregnant. She is a teacher in grade 1, and there is an epidemic of Fifth disease in the school where she teaches. Can this disease affect her pregnancy and how should I care for her? ANSWER: Erythema infectiosum (Fifth disease) is usually a benign disease for children and mothers, but might have serious consequences for a fetus due to hemolytic anemia, although the risk is very low. You should evaluate the mother's immune status. If she is already immune (IgG positive), the risks are nil. If she is not immune (although the risk of the fetus's being affected is very low), fetal surveillance by repeated ultrasonographic examination and immune status reevaluation has been recommended. If a fetus is found to be affected, intrauterine evaluation and treatment are available at tertiary care centres.

Adult↗

Maternal and obstetric effects of prenatal drug exposure.

Women addicted to recreational drugs are at a higher risk for a variety of obstetrical complications that may increase perinatal morbidity for mother and child. Because most of these women consume more than one recreational drug and are found to have a clustering of other psychosocial risk factors such as poverty and single motherhood, attention should be given to the complexity of all risks involved.

Female↗

Continuing drug therapy while breastfeeding. Part 1. Common misconceptions of patients.

QUESTION: Some of my patients who need specific drugs during the postpartum period are hesitant to breastfeed even when I tell them that, according to available evidence, these drugs are safe. Am I right about this and how should I advise my patients? ANSWER: Recent studies reveal that women receiving chronic therapy tend to initiate breastfeeding much less often than mothers in the general population and, if they do initiate, discontinue it much earlier. While reassuring counseling is generally correlated with continuation of breastfeeding, women receiving chronic medications still discontinue breastfeeding earlier. Stressing the clear benefits of breastfeeding and the lack of apparent risk of drugs shown to be safe should be coupled with repeated reassurance to mothers during close follow up of their babies.

Adult↗

Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children.

Ifosfamide is widely used in the treatment of pediatric solid tumors. Its main adverse effects are various forms of renal tubular and glomerular damage. The authors sought to determine factors that predict the risk for the development and severity of ifosfamide-induced nephrotoxicity in children and to examine the long-term outcome of this complication. A total of 174 children who had received ifosfamide for various cancers were studied. Nephrotoxicity was assessed by laboratory markers of glomerular and tubular function and a grading score (none, mild, moderate, severe). Patients were assessed 4 to 12 weeks after each ifosfamide course, 3 months after completion of chemotherapy, and 5 years later. Of 174 children, 72 (41.4%) developed tubular dysfunction, whereas only 11 (6.3%) demonstrated glomerular dysfunction; 40 (23.0%) demonstrated mild toxicity, 16 (9.2%) demonstrated moderate toxicity, and 16 (9.2%) developed severe nephrotoxicity. The four severity subgroups (none, mild, moderate, severe) received comparable doses/m2/cycle of ifosfamide and mesna. Children exhibiting severe toxicity were significantly younger compared to those with moderate, mild, or no nephrotoxicity (median age: 2.2, 7.0, 8.2, and 10.5 years, respectively; p < 0.001) and received significantly higher cumulative doses of ifosfamide (49.6 +/- 12.3, 46.0 +/- 13.1, 36.2 +/- 9.7, and 33.8 +/- 7.6 g/m2, respectively; p < 0.001). Cumulative doses of cisplatin were higher among children with severe nephrotoxicity compared to those with moderate, mild, or no toxicity, although this difference did not reach statistical significance. Of all risk factors analyzed by multiple regression analysis, age was the most significant predictor for the grade of nephrotoxicity (p < 0.001), followed by the cumulative dose of ifosfamide (p = 0.005). Seven out of 16 children (44.0%) with severe nephrotoxicity and 4 out of 16 children (25.0%) with moderate nephrotoxicity demonstrated severe chronic tubular toxicity over a follow-up period of 5 years. Since severe ifosfamide-induced renal toxicity tends to be chronic in a substantial number of treated children, it should be balanced carefully against efficacy. Cumulative ifosfamide doses of 45 g/m2 and above should be carefully considered, especially in children younger than age 3.

Adolescent↗

Continuing drug therapy while breastfeeding. Part 2. Common misconceptions of physicians.

QUESTION: Is there any way to predict whether a drug taken by a mother is safe for a suckling baby, or is it just trial and error? One of my patients is receiving lithium for manic depression. She wishes to breastfeed, but clinically there is no way she can discontinue the drug. My sources say the drug is incompatible with breastfeeding. ANSWER: The amount of drug available to a baby through breastmilk is estimated as the percentage of maternal dose per kg ingested by the baby. Because infants' clearance rate of many drugs is slower than adults', however, the true level of the drug circulating in the infant's blood might be much higher. Because lithium can be measured in plasma, it is prudent to measure it in milk and to estimate the "baby dose." If a baby shows any adverse effects, lithium levels should be measured in its blood.

Adult↗

Safe use of valproic acid during pregnancy.

QUESTION: I have an epileptic patient who plans pregnancy. It took us years to control her seizures, and valproic acid seems to be the only way to control them. What is the risk to her fetus? ANSWER: Neural tube defects (NTDs) are the most common of the major anomalies associated with in utero exposure to valproic acid. About 1% to 2% of exposed fetuses suffer adverse effects.

Adult↗

Prevalence and severity of nausea and vomiting of pregnancy and effect of vitamin supplementation.

OBJECTIVE: Although nausea and vomiting of pregnancy is the most common medical condition during pregnancy, there are many unanswered questions regarding its cause, epidemiologic features and optimal management. The objectives of this study were to ascertain the prevalence of nausea and vomiting in a sample of Canadian women, to characterize the distribution of their severity and to investigate the role of vitamin B6 deficiency in their etiology. DESIGN: Prospective study. SETTING: Antenatal counselling service for pregnant women. PATIENTS: Three cohorts of women: a prospective, population-based cohort of 193 women, to estimate the rate and severity of nausea and vomiting (cohort A); a cohort of 555 women who sought advice for nausea with or without vomiting, to study the correlation between the maximal daily number of episodes of vomiting and maximal weight loss (cohort B); and a prospective cohort of 301 women who reported vomiting, to correlate vitamin supplementation with vomiting (cohort C). INTERVENTIONS: All 3 cohorts were interviewed during the counselling session, and cohort B was followed up prospectively. OUTCOME MEASURES: Frequency of nausea and vomiting, weight loss, maximal number of daily episodes of vomiting, rate of multivitamin supplementation. RESULTS: Overall, 67% of the women in cohort A reported experiencing nausea or vomiting, or both; 22% reported vomiting, and 9% experienced weight loss. In cohort B there was a significant correlation between the maximal number of daily episodes of vomiting and maximal weight loss, although there was wide variation (r2 = 0.25, p < 0.001). There was a highly significant correlation between the number of daily vomiting episodes and mean weight loss (r2 = 0.99). In cohort C, vomiting was significantly associated with lack of supplementation with multivitamins before 6 weeks' gestation (p = 0.002). CONCLUSIONS: The relation between number of daily vomiting episodes and mean weight loss may serve as a clinical tool to assess the severity of nausea and vomiting in pregnancy and the success of anti-emetics and rehydration regimens. Further study is needed to elucidate the biologic basis of the observed association between vomiting and lack of multivitamin supplementation in early pregnancy.

Canada↗

Exposure to organic solvents. Does it adversely affect pregnancy?

QUESTION: One of my patients is a laboratory technician who routinely handles organic solvents. She has just learned that she is pregnant, and she depends very much on this job because her husband is unemployed. What is the risk to her unborn baby? ANSWER: Available epidemiologic data indicate your patient's fetus might be at increased risk for malformations. We recommend that she minimize her occupational exposure to organic solvents by routinely using ventilation systems and protective equipment. This is most important during the first trimester of pregnancy.

Adult↗

Congenital rubella syndrome. How can we do better?

QUESTIONMy 22-year-old patient immigrated to Canada 6 years ago from a country where there are no routine immunizations. She is now at 10 weeks' gestation and was exposed to a child with rubella infection. Her immune status is unknown. Should I give her passive or active immunization? How should I follow her pregnancy? And what should I tell her about the risk for her fetus?ANSWERIf the exposure took place less than 1 week ago, blood should be sent for rubella antibody titre. If results are positive for IgG, she is immune and there is no risk for the fetus. If a patient's immune status is unknown and the time of exposure is uncertain, serum samples for rubella antibodies should be obtained 3 weeks apart. Detection of rubella-specific IgM in a sample will confirm recent infection. Your patient should be counseled about the potential risk for her fetus and referred to high-risk pregnancy clinic for follow up. If seroconversion does not take place, she requires immunization immediately postpartum before discharge from hospital.

Adult↗

Preconception counseling and women's compliance with folic acid supplementation.

QUESTION: I am counseling patients to take folic acid when they plan pregnancy and during early pregnancy. Is there any proof that counseling really causes women to comply? ANSWER: A recent Motherisk study showed that counseling women who were planning pregnancy about folic acid use is very effective: 71% of those counseled took folic acid, compared with only 17% of those who were not counseled.

Adult↗

Dextromethorphan. Extrapolation of findings from reproductive studies in animals to humans.

QUESTION: One of my patients, who is now 8 weeks pregnant, just read in the newspaper that dextromethorphan (DM), an antitussive found in a variety of cough medicines, caused birth defects in chicken embryos. The author of the study stated that even one dose could be dangerous and that he would never allow his wife to use this drug if she were pregnant. My patient was understandably very concerned because last week she was suffering from a nasty cough and had been advised by her pharmacist to use a cough mixture containing DM, which she subsequently took for several days. ANSWER: You may reassure your patient that she did not put her baby at risk by using this substance. Dextromethorphan has been on the market for many years and has never been implicated as a human teratogen. Furthermore, chick embryos are not a good model for predicting teratogenic potential in humans and, consequently, were abandoned as such more than 30 years ago.

Abnormalities, Drug-Induced↗

Folic acid and neural tube defects. Good news at last!

QUESTION: I read last year that Canada has followed the United States in fortifying flour with folic acid to prevent neural tube defects. Do we know yet whether this strategy is working? ANSWER: In Canada, flour is fortified with folic acid to a level of 0.15 mg/100 g. Although a mandatory date was set for November 1, 1998, most if not all companies implemented the change on or before January 1, 1998. Recent figures from the United States, where the deadline for fortification was January 1998, show that by March 1999, mean folate levels in flour doubled, substantially decreasing the risk for neural tube defects.

Canada↗

Reproducibility of medical information obtained via the telephone vs personal interview.

The Motherisk [corrected] Program, a teratogenic information service, conducts patient interviews over the telephone as well as in a clinic setting. In both instances, medical information and exposure history is obtained from the patient, including such items as pregnancy history, drug exposure, alcohol and smoking habits. It occurred on several occasions that the clinic interviewer remarked that the same patient had volunteered information to them, that differed from the information documented on the intake telephone form. The objective of the study was to establish the levels of agreement in the documentation, between these two forms of interviews. Two groups of 100 paired telephone and clinic forms were randomly selected from our data base, 1990-1991 and 1996-1997. These two groups were chosen to assess if there were any differences over a five year time period. Statistical calculations were performed using the Kappa statistic, a method that measures agreement. Kappa scores indicated high reproducibility for both pregnancy and smoking history, good reproducibility for medical history, marginal-good for exposures (although excellent agreement was found for the primary drug of concern) and marginal-good for alcohol information. Overall, agreement was superior in the 1990-1991 group. There were marked differences in consistency, between the information recorded on the telephone form and the clinic form, most specifically relating to secondary exposures and alcohol history. It suggests that a person to person interview yields a more complete medical history than a telephone interview.

Alcohol Drinking↗

Antimalarial drugs for rheumatoid disease during pregnancy.

QUESTION: One of my patients, who has rheumatoid arthritis, has just found out she is pregnant. She is being treated with hydroxychloroquine. I could not find anything about the safety of this drug during pregnancy. ANSWER: Most of the literature on this drug relates to prophylaxis for malaria. Much lower doses than those used for rheumatic diseases are given with no adverse fetal effects. Several studies on use of the drug for rheumatic diseases during pregnancy also failed to show adverse fetal effects, although, in most cases, only first-trimester exposure was reported.

Antimalarials↗

Occupational exposure to mercury. What is a safe level?

QUESTION: One of my pregnant patients, a dental hygienist, uses mercury in her workplace, but appears to have no symptoms of mercury toxicity. She has heard that mercury might affect her fetus. What should I recommend to her? What is a safe level of mercury in the air for pregnant women? ANSWER: Testing for levels of mercury in whole blood and, preferably, urine is useful for confirming exposure. Currently, mercury vapour concentrations greater than 0.01 mg/m3 are considered unsafe. Also, women of childbearing age should avoid contact with mercury salts in the workplace.

Dental Hygienists↗