Achilles tendon rupture and its association with fluoroquinolone antibiotics and other potential risk factors in a managed care population

BACKGROUND: Case reports and observational studies have implicated fluoroquinolone antibiotic exposure as a risk factor for Achilles tendon rupture (ATR), an uncommon condition for which there are few formal studies. We sought to quantify the strength of association between exposure to fluoroquinolone antibiotics and the occurrence of ATR, accounting for other risk factors. METHODS: This was a case-control study nested within a health insurer cohort. Cases of ATR were identified and confirmed using patterns of health insurance claims that were validated through sampled medical record review. Information on risk factors, including fluoroquinolone exposure, came from health insurance claims. RESULTS: There were 947 cases of ATR and 18 940 controls. A dispensing of a fluoroquinolone antibiotic in the past 6 months was more common among ATR cases than controls, although not significantly so (odds ratio (OR) = 1.2; 95% confidence interval (CI) = 0.9-1.7), and exposure to a higher cumulative fluoroquinolone dose was more strongly associated (OR = 1.5, 95%CI = 1.0-2.3). Other risk factors for ATR were trauma (OR = 17.2, 95%CI = 14.0-20.2), male sex (OR = 3.0, 95%CI = 2.6-3.5), injected corticosteroid administration (OR = 2.2, 95%CI = 1.6-2.9), obesity (OR = 2.0, 95%CI = 1.2-3.1), rheumatoid arthritis (OR = 1.9, 95%CI = 1.0-3.7), skin or soft tissue infections (OR = 1.5, 95%CI = 0.9-2.3), oral corticosteroids (OR = 1.4, 95%CI = 1.0-1.8), and non-fluoroquinolone antibiotics (OR = 1.2, 95%CI = 1.1-1.5). CONCLUSIONS: The elevation in ATR risk associated with fluoroquinolones was similar in magnitude to that associated with oral corticosteroids or non-fluoroquinolone antibiotics. Trauma and male sex were more strongly associated with ATR, as were obesity and injected corticosteroids.     

Acid-suppressing drugs and gastroesophageal reflux disease as risk factors for acute pancreatitis--results from a Swedish Case-Control Study

PURPOSE: To study risk factors for acute pancreatitis, here with emphasis on gastro-intestinal diseases and their treatments. METHODS: Population based case-control study covering four areas in Sweden encompassing 2.2 million inhabitants. Included were 462 incident cases of acute pancreatitis aged 20-85 years, hospitalized from 1 January 1995-31 May 1998, and 1,781 unmatched controls randomly selected from the study base using a population register. Information was captured from medical records and structured telephone interviews. RESULTS: Current use of H(2) antagonists starting within 6 months of index-date was associated with acute pancreatitis with an adjusted OR of 4.9 (95% confidence interval (CI) 1.6-15), and current use of proton pump inhibitors (PPIs) with an adjusted OR of 3.2 (95%CI 1.4-7.4). For both drug classes, the ORs tended to be higher at higher doses. Gastritis/gastro-esophageal reflux disease (GERD) within the last 12 months not treated with PPIs or H(2)-antagonists and inflammatory bowel disease (IBD) not treated with anti-inflammatory or immunosuppressive drugs were associated with development of acute pancreatitis with adjusted odds ratios (OR) of 1.9 (95%CI 1.2-3.0) and 5.1 (95%CI 2.0-13) respectively. CONCLUSIONS: Current IBD without treatment and gastritis/GERD without treatment were found to be associated with increased risks to develop acute pancreatitis but the nature of the latter association needs to be further evaluated. On balance, we judge that the observed associations between current use of H(2)-antagonists and PPIs and increased risk of acute pancreatitis are unlikely to be explained by bias.     

The possible association between the combination of vaginal metronidazole and miconazole treatment and poly-syndactyly Population-based case-control teratologic study

The objective of the study was to investigate the human teratogenic potential of vaginal metronidazole+miconazole treatment during pregnancy, because these antimicrobial drugs separately did not indicate human teratogenic potential in our and other studies. The analysis of cases with 21 groups of congenital abnormalities and their all matched controls was carried out in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 including 38,151 pregnant women who had newborn infants without any congenital abnormalities (control group) and 22,843 pregnant women who had newborn infants or fetuses with congenital abnormalities. The prevalence of vaginal metronidazole+miconazole treatment during pregnancy was 2.5% (N=576) in the case group and 2.2% (N=846) in the control group [crude prevalence odds ratio (POR) with 95% confidence interval (CI): 1.2, 1.0-1.3]. The analysis of cases and their matched controls indicated an association between vaginal metronidazole+miconazole use and poly/syndactyly during the second through third months of gestation (adjusted POR 6.0, 95% CI 2.4-15.2). This finding may be connected with recall bias, although this bias was restricted by the evaluation of maternal drug use only during the critical period of poly/syndactyly and by evaluating only medically recorded metronidazole+miconazole treatment. The conclusion of the study is that this finding can be regarded as a signal for the possible association between vaginal treatment of metronidazole+miconazole during pregnancy and poly/syndactyly without any plausible biological hypothesis.     

Prenatal, perinatal and neonatal risk factors for autism - study in Poland

The results of conducted research studies suggest that heredity and early fetal and neonatal development play a causal role in autism. The objective was to determine a relationship between pre-, peri-, and neonatal factors and autism. The relationship between genders and individual risk factors for autism was also examined. A case-control study was conducted among 288 children (96 cases with childhood or atypical autism and 192 controls individually matched to cases by the year of birth, sex, and general practitioners). Data on autism diagnosis and other medical conditions were acquired from physicians. All other information on potential autism risk factors were collected from mothers. Autism risk was significantly higher when mothers were taking medications (OR=2.72, 95%CI: 1.47-5.04) and smoked during pregnancy (OR=3.32, 95%CI: 1.12-9.82). It was also significantly associated with neonatal dyspnea (OR=3.20, 95%CI: 1.29-8.01) and congenital anomalies (OR=7.17, 95%CI: 2.23-23.1). In gender analysis only congenital anomalies were significantly associated with autism for girls but all of mentioned factors stayed independent risk factors for boys.     

Use of psychotropic drugs in 0 to 5 years old children in Aquitaine (France): prevalence and associated factors

PURPOSE: To describe the use of psychotropic drugs in children aged 0-5 years, in the Aquitaine region of South-west France and identify associated socio-demographic, familial and medical factors. METHODS: Data used in this study come from the regional drug claims database of the National Health Insurance System of Aquitaine and from postal self-questionnaires sent to parents and prescribing physicians. RESULTS: In Aquitaine, psychotropic drugs were redeemed at least once in 2002 for 3.2% of young children. Hydroxyzine, niaprazide or diazepam were claimed at least once by 2.7% of children registered in the database. Prescribers were mostly general practitioners (76.7%) and pediatricians (20.1%). Psychotropic claims were more frequent in children having the highest number of medical consultations in 2002 (more than 7: odds ratio (OR) = 1.5 [95% confidence interval (CI): 1.3-1.7]) or of drug deliveries (7-15 deliveries: OR = 1.8 [95%CI: 1.6-2.1]; more than 15 deliveries: OR = 3.2 [95%CI: 2.7-3.9]). Psychotropic claim frequency increased with age. No association of psychotropic use with parental psychotropic use, socio-professional category and familial situation was found. CONCLUSIONS: Psychotropic delivery prevalence in Aquitaine in young children was below 5% in 2002. It notably concerned drugs of which the use is not devoid of toxicity because of anticholinergic properties.     

Pharmacology of antiepileptic drugs in the gerbil—I. Pharmacokinetics

Pharmacokinetic data for antiepileptic drugs were determined in gerbils. The drugs had the following elimination half-lives: phenytoin 2.1 hr; phenobarbital 10.6 hr; carbamazepine 1.8 hr; valproate 0.69 hr; ethosuximide 1.4 hr and diazepam 1.15 hr. Diazepam was predominantly metabolized via 3-hydroxydiazepam to oxazepam which had the longest half-life (2 hr) of the metabolites.     

Adverse reactions of anti-tuberculosis drugs in hospitalized patients: incidence, severity and risk factors

BACKGROUND: Tuberculosis (TB) has been a common chronic infectious disease in human communities. Besides disease-related complications, there could be serious adverse reactions due to anti-tuberculosis (anti-TB) drug therapy. OBJECTIVES: To assess the incidence and severity of adverse drug reactions (ADRs) induced by anti-TB drugs. To determine possible covariates associated with detected ADRs. METHODS: All patients with respiratory TB admitted to a teaching hospital who received anti-TB drugs during the research period entered the study and were monitored for ADRs. Socio-demographic and medical history of patients were used as independent covariates. The relationship between independent covariates with frequency and severity of ADRs was analysed using multivariate logistic regression. Preliminary analyses of the Mann-Whitney, Chi-square, Kruskal-Wallis and the Fisher's exact tests were applied to determine factors unlikely associated with the independent variables. RESULTS: Among 204 patients admitted, there were 92 patients (45.1%) with ADRs induced by anti-TB drugs. Patients with a previous history of anti-TB drugs usage (OR = 5.81, 95% confidence interval [95%CI]: 1.31-25.2), patients with a history of drug allergy (OR = 6.68, CI: 1.28-36.2), those from Afghani ethnic (OR = 4.91, 95%CI: 1.28-18.30) as well as smoker patients with concurrent diseases (OR = 19.67, CI: 1.24-341.51) had a higher rate of ADR incidence. Being female (OR = 1.63, 95%CI: 1.96-36.40) and having previous history of ADR (OR = 17.46, 95%CI: 1.96-20.42) were identified as risk factors. CONCLUSION: Anti-TB drugs could cause severe and frequent adverse effects. Females, those with a previous history of ADRs to anti-TB drugs and Afghani patients, should be considered as high-risk groups.     

A population-based case-control teratologic study of promethazine use during pregnancy

Objective of the study was to investigate the teratogenic effect of oral promethazine, a phenothiazine derivate in the population-based data set of the Hungarian Case–Control Surveillance of Congenital Abnormalities during the years 1980–1996. Of 22,843 cases with 25 congenital abnormalities, 3648 (16.0%) were born to mothers treated orally with promethazine during pregnancy. Of 38,151 matched population controls without congenital abnormalities, 6025 (15.8%) had mothers with promethazine treatment during the study pregnancy. Of 834 malformed controls (Down syndrome), 142 (17.0%) had mothers with treatment of promethazine in the study pregnancy. The case-all matched population controls analysis showed a higher rate of cleft lip ± cleft palate (adjusted OR with 95% CI: 1.5, 1.1–2.0) and poly/syndactyly (OR with 95% CI: 1.3, 1.0–1.8) after promethazine treatment during the 2nd and 3rd months of gestation. However, these risks were explained by recall bias, because these associations were not confirmed after the evaluation of only medically recorded promethazine uses. The comparison of promethazine treatment between 25 congenital abnormality groups and malformed controls did also not show any risk. Thus, the overall evidence from analysis presented did not suggest that clinical doses of promethazine increased the rate of congenital abnormalities in humans.     

Exploring the drug-induced anemia signals in children using electronic medical records

ABSTRACT

Objectives: The objectives were to identify drugs related with anemia in children and evaluate the novelty of these correlations.

Methods: The authors established a two-step method for detecting the relationship between drugs and anemia using electronic medical records (EMRs), which were obtained from 247,136 patients in Beijing Children’s Hospital between 2007 and 2017. The authors extracted potential drugs by mining cases for hemoglobin abnormalities from the EMR and then performed a retrospective cohort study to correlate them with anemia by calculating the matched odds ratios and 95% confidence interval using unconditional logistic regression analysis.

Results: In total, nine positive drug-anemia associations were identified. Among them, the correlations of drugs fluconazole (OR 3.95; 95%CI: 2.65–5.87) and cefathiamidine (OR 3.49; 95%CI: 2.94–4.15) with anemia were considered new signals in both children and adults. Three associations of drugs, vancomycin, cefoperazone-sulbactam and ibuprofen, with anemia were considered new signals in children.

Conclusion: The authors detected nine signals of drug-induced anemia, including two new signals in children and adults and three new signals in children. This study could serve as a model for using EMR and automatic mining to monitor adverse drug reaction signals in the pediatric population.     

Comparison of equilibrium dialysis, ultrafiltration, and gel permeation chromatography for the determination of free fractions of phenobarbital and phenytoin

In this study, three techniques for measuring the free fractions of phenobarbital and phenytoin were compared: equilibrium dialysis, ultrafiltration, and the Hummel and Dreyer method for gel permeation chromatography. In their therapeutic range (15-40 and 10-20 mg/L, respectively) the free fractions of phenobarbital and phenytoin were independent of the drug concentrations. Free fractions of phenobarbital as determined by equilibrium dialysis, ultrafiltration, and gel permeation chromatography were 58.7 +/- 1.8, 58.3 +/- 1.5, and 55.1 +/- 1.7%, respectively. Free fractions of phenytoin were 18.1 +/- 1.1, 17.0 +/- 2.1, and 19.4 +/- 1.2%, respectively. On lowering the albumin concentration, a similar increase in the free fractions of both drugs was observed with all three techniques. The results of this study show that all three techniques are suitable for the determination of free fractions of phenobarbital and phenytoin. Moreover, these techniques seem to be suitable for the investigation of physiological factors that may influence albumin drug binding.     

Anticonvulsant potency of common antiepileptic drugs in the gerbil

In gerbils, 'minor' (myoclonic) and 'major' (clonic-tonic) seizures were induced by blowing at the animals with compressed air. The anticonvulsant ED50 of the following drugs was determined after oral administration against both types of seizures: phenytoin, phenobarbital, carbamazepine, sodium valproate, ethosuximide, and diazepam. Valproate, ethosuximide, and diazepam were most potent against 'minor' seizures which could not or only partially be suppressed by phenytoin or carbamazepine, respectively. The 'grand mal' drugs phenytoin, phenobarbital, and carbamazepine were, on the other hand, more potent against 'major' than against 'minor' seizures. When phenobarbital was administered for several days, a strong induction of hepatic microsomal enzymes occurred.     

The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study

Objective: To study human teratogenic potential of two trimethoprim-sulfonamide combinations: trimethoprim-sulfamethoxazole (cotrimoxazole) and trimethoprim-sulfamethazine during pregnancy. These agents have antifolate effects and other antifolate agents can induce multiple congenital abnormalities, neural-tube defects, cardiovascular, and other malformations in animal experiments and in humans.

Design: Pair analysis of cases with congenital abnormalities and matched healthy controls in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996.

Participants: 38,151 pregnant women who had newborn infants without any congenital abnormalities (control group) and 22,865 case pregnant women who had newborns or fetuses with congenital abnormalities.

Main Outcome: Prevalence of drug use in matched case-control pairs to study the possible association with congenital abnormalities.

Results: In the case group 351 (1.5%) and in the control group 443 (1.2%) pregnant women were treated with cotrimoxazole (crude OR 1.3 with 95% CI 1.1–1.5). In addition 45 (0.2%) case and 39 (0.1%) control pregnant women had trimethoprim-sulfamethazine treatment (crude OR 1.9 with 95% CI 1.3–3.0). A higher rate of multiple congenital abnormalities (including mainly urinary tract and cardiovascular abnormalities) was found in case infants born to mothers with cotrimoxazole treatment during the second-third months of pregnancy. In addition, a higher rate of cardiovascular malformations occurred in cases born to mothers with cotrimoxazole treatment and trimethoprim-sulfamethazine treatment during the second-third months of pregnancy, respectively.

Conclusion: Treatment with cotrimoxazole during pregnancy may increase the risk of cardiovascular malformations, and particularly multiple congenital abnormalities including defects of the urinary tract and cardiovascular system. A higher rate of cardiovascular malformations was also found after treatment with trimethoprim-sulfamethazine in the second-third months of pregnancy.     

Population-based case control study of the safety of sulfasalazine use during pregnancy

BACKGROUND: We studied the human teratogenic risk of sulfasalazine because this drug interferes with folate metabolism. METHODS: Case control study within the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980-1996; based on 22 865 new-born infants or foetuses with congenital abnormalities, and 38 151 babies without any detected congenital abnormalities (control group). RESULTS: Seventeen pregnant women (0.07%) were treated with sulfasalazine in the case group, and 26 (0.07%) in the control group. The overall adjusted adds ratio of congenital abnormalities after sulfasalazine treatment was odds ratio = 1.2 (95% confidence interval: 0.6-2.1). None of the analyses indicated any significant increased prevalence of selected congenital abnormalities among the exposed compared with the not exposed. CONCLUSIONS: We found no significant increased prevalence of selected congenital abnormalities in the children of women treated with sulfasalazine during pregnancy. However, the amount of information is limited and additional data are needed to rule out a teratogenic effect.     

Antivirals and antibiotics for influenza in the United States, 1995--2002

PURPOSE: To measure the rates of antiviral and antibiotic prescribing for patients diagnosed with influenza in the United States. METHODS: We performed a retrospective analysis of visits to ambulatory clinics and emergency departments in the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) with a diagnosis of influenza that occurred in seven influenza seasons between 1 October 1995 and 31 May 2002 (n=1216). RESULTS: There were an estimated 22 million visits (95%CI, 17--26 million visits) with a diagnosis of influenza to community ambulatory clinics (88% of visits), hospital ambulatory clinics (3%) and emergency departments (9%) in the United States between the 1995--1996 and the 2001--2002 influenza seasons, inclusive. The sample was 63% adults, 44% male and 84% white. Physicians prescribed antivirals in 19% of visits and antibiotics not associated with an antibiotic-appropriate diagnosis in 26% of visits. In multivariable modeling, independent predictors of antiviral prescribing were adult age (OR, 2.1; 95%CI, 1.1--4.0) and Medicare insurance (OR, 0.1 compared to private insurance; 95%CI, 0.0--0.6). Antiviral prescribing was marginally associated with influenza season (OR, 1.2 per influenza season; 95%CI, 1.0--1.4). Independent predictors of antibiotic prescribing were influenza season (OR, 0.8 per influenza season; 95%CI, 0.7--0.9), male sex (OR, 0.6; 95%CI, 0.4--0.9), adult age (OR, 2.3; 95%CI, 1.2--4.2) and emergency department visits (OR, 0.5 compared to community ambulatory visits; 95%CI, 0.3--0.8). CONCLUSIONS: Physicians prescribed antiviral medications to 19% of patients they diagnosed with influenza; the proportion that would have been clinically appropriate is unknown. In contrast, physicians prescribed apparently inappropriate antibiotics to 26% of these same patients, a rate that, encouragingly, decreased over time.     

马来酸桂哌齐特注射液治疗脑卒中安全性的meta分析CSCD

目的系统评价马来酸桂哌齐特注射液(桂哌齐特)在脑卒中患者中应用的安全性。方法检索国内外相关数据库截至2020年12月31日收录的文献,收集桂哌齐特联合或不联合基础治疗(试验组)与基础治疗和除桂哌齐特外的其他药物单独或联用治疗(对照组)脑卒中的随机对照试验(RCT),结局指标含治疗相关不良事件(包括头痛、失眠、嗜睡、皮肤瘙痒等症状和肝、肾功能和血液系统等实验室指标异常)。采用Cochrane偏倚风险评估工具(5.1.0版)进行方法学质量评价,采用RevMan 5.3统计软件进行meta分析。效应值为相对危险度(RR)及其95%置信区间(CI)。结果纳入分析的RCT共19项,均为在我国开展的上市后研究。19项RCT共包括3272例患者,试验组1650例,对照组1622例。质量评价结果显示,研究存在选择性偏倚和测量偏倚可能。meta分析结果显示,试验组与对照组总体不良事件发生率差异无统计学意义[6.90%(114/1650)比7.64%(124/1622),RR=0.92,95%CI:0.72~1.17,P=0.49]。对按照剂量(80、160、240、320和400 mg/d)划分的5个亚组分析结果显示,试验组与对照组不良事件发生率差异均无统计学意义[8.77%(10/114)比14.16%(16/113),RR=0.62,95%CI:0.29~1.31,P=0.21;3.51%(4/112)比0(0/101),RR=4.58,95%CI:0.55~38.49,P=0.16;0.88%(1/114)比1.85%(2/108),RR=0.64,95%CI:0.10~3.86,P=0.62;7.53%(96/1275)比8.30%(105/1265),RR=0.92,95%CI:0.71~1.19,P=0.51;8.57%(3/35)比2.86%(1/35),RR=3.00,95%CI:0.33~27.46,P=0.33]。关注的几种不良事件meta分析结果显示,头痛、头晕、失眠、恶心、皮疹/瘙痒及白细胞减少等不良事件在试验组和对照组中的发生率差异均无统计学意义[3.45%(57/1650)比3.45%(56/1622),RR=1.02,95%CI:0.70~1.47,P=0.46;2.24%(37/1650)比2.40%(39/1622),RR=0.95,95%CI:0.60~1.51,P=0.76;0.84%(41/1650)比2.10%(34/1622),RR=1.23,95%CI:0.77~1.94,P=0.69;0.67%(11/1650)比0.12%(2/1622),RR=0.96,95%CI:0.39~2.39,P=0.64;0.36%(6/1650)比0.37%(6/1622),RR=1.06,95%CI:0.45~2.49,P=0.89;0.06%(1/1578)比0(0/1552),RR=3.00,95%CI:0.12~74.47,P=0.50]。结论国内上市的桂哌齐特临床安全性良好。     

A population-based case-control teratologic study of oral dipyrone treatment during pregnancy.

OBJECTIVE: To study the possible human teratogenic effect of oral dipyrone, an antipyretic and analgesic drug treatment during pregnancy. DESIGN AND SETTING: The analysis of cases with different congenital abnormalities and their matched population controls without congenital abnormalities, in addition to a comparison between cases and malformation controls (Down's syndrome) in the population-based, large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. STUDY PARTICIPANTS: 22 843 neonates or fetuses with congenital abnormalities (cases), 38 151 matched newborns without congenital abnormalities (population controls) and 834 neonates or fetuses with Down's syndrome (malformation controls). MAIN OUTCOME MEASURES: 25 congenital abnormality groups. RESULTS: 1382 (6%) cases, 1911 (5%) population controls and 74 (8.9%) malformation controls were born to mothers treated with dipyrone during pregnancy. The case-matched population control analysis showed a higher rate of diaphragmatic defect (adjusted prevalence odds ratio [POR] 2.7; 95% CI 1.0, 6.8), cardiovascular malformations (POR 1.3; 95% CI 1.0, 1.7) and other isolated congenital abnormalities (POR 1.8; 95% CI 1.1, 2.9) after oral dipyrone treatment during the second and third months of gestation, i.e. in the critical period for most major congenital abnormalities. However, the evaluation of only medically recorded dipyrone use did not confirm these possible associations. The comparison of dipyrone treatment between 25 congenital abnormalities groups and malformation controls as the referent group also did not show any difference in the dipyrone use during the second and third months of gestation. CONCLUSIONS: The higher occurrence of dipyrone treatment in the case mothers compared with population control mothers can be explained by recall bias and/or chance. However, the higher rate of diaphragmatic congenital abnormalities can be considered as a signal and merits further investigation.     

Drug therapy reviews: drug therapy of status epilepticus.

Drug treatment of status epilepticus is reviewed. Tonic-clonic, focal motor, complex partial and absence status epilepticus are discussed. In managing tonic-clonic status epilepticus one should: (1) maintain vital functions at all times, (2) identify and treat precipitating factors and (3) administer an intravenous loading dose of phenytoin sodium or phenobarbital sodium. Careful use of i.v. diazepam sometimes helps to achieve these objectives. Intravenous phenytoin sodium and phenobarbital sodium provide definitive, long-term control of tonic-clonic seizures but must be administered slowly and require time to reach peak brain concentrations. Intravenous diazepam appears to enter and exit from the brain rapidly and may control seizures while therapeutic brain concentrations of long-acting drugs are being achieved. Phenytoin, phenobarbital and diazepam should not be administered intramuscularly in treating status epilepticus. Treatment of focal motor and complex partial status epilepticus is similar to that of tonic-clonic status epilepticus, but i.v. diazepam is required less frequently and loading doses of phenytoin and phenobarbital sometimes can be given more slowly. Status epilepticus of the absence type is managed with i.v. acetazolamide sodium or diazepam. Paraldehyde, muscle relaxants, general anesthesia and lidocaine may be tried when conventional therapies fail.     

Tolnaftate spray treatment during pregnancy

Teratogenic studies of tolnaftate, an antifungal agent, in humans have not been published. The population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 contained 22843 fetuses or newborns with congenital abnormalities and 38151 matched controls without congenital abnormalities. The mothers of 13 cases and 13 controls were treated with tolnaftate spray during pregnancy. Four cases had congenital cardiovascular malformations in the group of cases (OR with 95% CI: 3.1, 1.0-9.7), but these cardiac defects were different. Thus, it is a signal for the potential teratogenic risk of tolnaftate in a case-control study, though the number of cases and controls were limited. Therefore, international collaboration is needed for the final conclusion.