bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between Anticonvulsants and Human Placental Carnitine Transporter
Authors: Wu Shu‐Pei , Shyu Ming‐Kwang , Liou Horng‐Huei , Gau Churn‐Shiouh , Lin Chun‐Jung
Published: February 2004

Summary:  Purpose: To examine the inhibitory effect of anticonvulsants (AEDs) on carnitine transport by the human placental carnitine transporter.

Methods: Uptake of radiolabeled carnitine by human placental brush‐border membrane vesicles was measured in the absence and presence of tiagabine (TGB), vigabatrin (VGB), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), valproic acid (VPA), and phenytoin (PHT). The mechanism of the inhibitory action of TGB was determined.

Results: Most of the AEDs inhibited placental carnitine transport. Kinetic analyses showed that TGB had the greatest inhibitory effect [50% inhibitory concentration (IC50, 190 μM)], and the order of inhibitory potency was TGB > PHT > GBP > VPA > VGB, TPM > LTG. Further studies showed that TGB competitively inhibited carnitine uptake by the human placental carnitine transporter, suggesting that it may be a substrate for this carrier.

Conclusions: Although the involvement of carnitine deficiency in fetal anticonvulsant syndrome requires further evaluation, potential interference with placental carnitine transport by several AEDs was demonstrated. Despite the higher inhibitory potency of TGB, given the therapeutic unbound concentrations, the results for VPA and PHT are probably more clinically significant.
Long‐term Cognitive Outcomes of a Cohort of Children with Cryptogenic Infantile Spasms Treated with High‐dose Adrenocorticotropic Hormone
Authors: Kivity Sara , Lerman Pinchas , Ariel Raya , Danziger Yardena , Mimouni Marc , Shinnar Shlomo
Published: February 2004

Summary:  Purpose: To evaluate the outcome of children with cryptogenic infantile spasms treated with high‐dose synthetic adrenocorticotropic hormone (ACTH) and the relation between early treatment, within 1 month of onset, and outcome.

Methods: We assessed the long‐term cognitive and seizure outcomes of 37 patients with cryptogenic infantile spasms (onset, age 3 to 9 months) receiving standardized treatment regimen of high‐dose tetracosactide depot, 1 mg IM every 48 h for 2 weeks, with a subsequent 8‐ to 10‐week slow taper and followed by oral prednisone, 10 mg/day for a month, with a subsequent slow taper for 5 months or until the infant reached the age of 1 year, whichever came later. Development was assessed before treatment. Seizure outcomes were followed up prospectively. Cognitive outcomes were determined after 6 to 21 years and analyzed in relation to treatment lag and pretreatment regression.

Results: Twenty‐two infants were treated within 1 month of onset of infantile spasms, and 15 after 1 to 6.5 months. Normal cognitive outcome was found in all 22 (100%) patients of the early‐treatment group, and in 40% of the late‐treatment group. Normal cognitive outcome was found in all 25 (100%) patients who had no or only mild mental deterioration at presentation, including four in the late‐treatment group but in only three of the 12 patients who had had marked or severe deterioration before treatment.

Conclusions: Early treatment of cryptogenic infantile spasms with a high‐dose ACTH protocol is associated with favorable long‐term cognitive outcomes. Once major developmental regression lasts for a month or more, the prognosis for normal cognitive outcome is poor. Further studies are needed on the optimal treatment regimen for this disorder.
Epilepsy Surgery for Pathologically Proven Hippocampal Sclerosis Provides Long‐term Seizure Control and Improved Quality of Life
Authors: Lowe Adrian J. , David Efraim , Kilpatrick Christine J. , Matkovic Zelko , Cook Mark J. , Kaye Andrew , O'Brien Terence J.
Published: February 2004

Summary:  Purpose: To examine long‐term seizure and quality‐of‐life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippocampal sclerosis (HS). Previous research has had limited follow‐up (generally <2 years) and has grouped patients across multiple pathologies.

Methods: Fifty consecutive patients were identified as having had a temporal lobectomy for the treatment of temporal lobe epilepsy at Royal Melbourne Hospital with pathologically proven HS and ≥2 years' follow‐up. All patients were sent a postal survey concerning seizure activity, quality of life (QOLIE‐89), and antiepileptic drug (AED) use. The mean follow‐up was 5.8 years (range, 2–9.2).

Results: The rate of complete postoperative seizure freedom was 82% at 12 months, 76% at 24 months, and 64% at 63 months (no further seizure recurrences observed after this time). A class I seizure outcome was achieved by 83.3% of patients. Patients with better seizure outcome had significantly better quality of life (Kendall's tau =–234, p < 0.01). Seizure recurrence was associated with a reduction in AED intake or absorption in five (29%) of 17 cases, including three of the five patients with a first seizure recurrence after 24 months after surgery.

Conclusions: Temporal lobectomy provides continued long‐term seizure control in the majority of patients with HS. However, patients remain at risk of seizure recurrence ≥2 years after surgery. Long‐term quality of life is dependent on seizure outcome.
Evidence for Linkage between Juvenile Myoclonic Epilepsy–Related Idiopathic Generalized Epilepsy and 6p11‐12 in Dutch Families
Authors: Pinto Dalila , De Haan Gerrit‐Jan , Janssen Guus A. M. A. J. , Boezeman Eduard H. , Van Erp M. Gerard , Westland Birgit , Witte Jorine , Bader Adri , Halley Dicky J. J. , Kasteleijn‐Nolst Trenité Dorothée G. A. , Lindhout Dick , Koeleman Bobby P. C.
Published: February 2004

Summary:  Purpose: Previous linkage studies provided evidence for juvenile myoclonic epilepsy (JME) susceptibility loci at 6p11‐12, HLA‐6p21.3 region, 15q14, and 5q34. These results indicate locus heterogeneity or interpopulation differences, thus underlining the importance of replication studies.

Methods: We describe a replication linkage study of the 6p‐q13 region in 18 families ascertained from JME probands of Dutch descent. In the presence of heterogeneity, the definition of the disease status may be crucial, and we therefore used two disease phenotypes: narrow [JME/idiopathic generalized epilepsy (IGE)‐“only”] and broad (JME/IGE‐plus‐fast EEG background activity).

Results: We found evidence of linkage at 6p11‐12 in multipoint analyses (p < 0.01 in a replication study) for both these disease definitions. Analysis of this region, assuming heterogeneity and autosomal dominant inheritance with a conservative 60% of penetrance, gave a maximum multipoint parametric lod score of 2.07 at D6S1573 for the narrow phenotype and peaked at 2.53 between D6S1623 and D6S1573 for the broad phenotype. The p value for nonparametric linkage reached 0.0013 for the narrow phenotype and 0.0010 for the broad. Significant exclusion (lod score ≤2) was found for the HLA region and for 10 to 30 cM telomeric to HLA. Our results provide evidence for a susceptibility locus for JME/IGE‐plus‐fast EEG background activity at 6p11‐12.

Conclusions: Additionally, by using a narrow definition, we were able to confirm previous evidence for a JME–IGE locus at this location.
Specific Epileptic Syndromes Are Rare Even in Tertiary Epilepsy Centers: A Patient‐oriented Approach to Epilepsy Classification
Authors: Kellinghaus Christoph , Loddenkemper Tobias , Najm Imad M. , Wyllie Elaine , Lineweaver Tara , Nair Dileep R. , Lüders Hans O.
Published: February 2004

Summary:  Purpose: To assess the practicability and reliability of a five‐dimensional patient‐oriented epilepsy classification and to compare it with the International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The dimensions consist of the epileptogenic zone, semiologic seizure type(s), etiology, related medical conditions, and seizure frequency.

Methods: The 185 epilepsy patients (94 adults, 91 children, aged 18 years or younger) were randomly selected from the database of a tertiary epilepsy center and the general neurological department of a metropolitan hospital (28 adults). The charts were reviewed independently by two investigators and classified according to both the ILAE and the patient‐oriented classification. Interrater reliability was assessed, and a final consensus among all investigators was established.

Results: Only four (4%) adults and 19 (21%) children were diagnosed with a specific epilepsy syndrome of the ILAE classification. All other patients were in unspecific categories. The patient‐oriented classification revealed that 64 adults and 56 children had focal epilepsy. In an additional 34 adults and 45 children, the epileptogenic zone could be localized to a certain brain region, and in 14 adults and five children, the epileptogenic zone could be lateralized. Fourteen adults and 21 children had generalized epilepsy. In 16 adults and 14 children, it remained unclear whether the epilepsy was focal or generalized. Generalized simple motor seizures were found in 66 adults and 52 children, representing the most frequent seizure type. Etiology could be determined in 40 adults and 45 children. Hippocampal sclerosis was the most frequent etiology in adults (10%), and cortical dysplasia (9%), in children. Seven adults and 31 children had at least daily seizures. Seventeen adults and 26 children had rare or no seizures at their last documented contact. The most frequent related medical conditions were psychiatric disorders and mental retardation. Interrater agreement was high (kappa values of 0.8 to 0.9) for both the patient‐oriented and the ILAE classification.

Conclusions: Specific epilepsy syndromes included in the current ILAE classification are rare even in a tertiary epilepsy center. Most patients are included in unspecific categories that provide only incomplete information. In contrast, all of the patients could be classified by the five‐dimensional patient‐oriented classification, providing all essential information for the management of the patients with a high degree of interrater reliability.
Benign Focal Epileptiform Discharges of Childhood and Hippocampal Sclerosis
Authors: Pan Andrew , Gupta Ajay , Wyllie Elaine , Lüders Hans , Bingaman William
Published: February 2004

Summary:  Purpose: Benign focal epileptiform discharges of childhood (BFEDCs) are common EEG findings between ages 4 and 14 years. This epoch of maturational development overlaps with the age at presentation of temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) in children.

Methods: From our series of 17 preadolescent children who eventually underwent anteromesial temporal resection for medically refractory TLE due to HS, we identified two children, plus one thereafter, who were initially dismissed as candidates for epilepsy surgery because of abundant extratemporal sharp waves, which were bilateral in two cases. The sharp waves had the distinctive morphology, distribution, and sleep activation suggestive of BFEDCs, but the medical intractability and seizure symptoms were unusual for benign focal epilepsy of childhood.

Results: In each case, surgical candidacy was clarified when magnetic resonance imaging (MRI) showed unilateral HS and video‐EEG demonstrated seizure onset in the ipsilateral anteromesial temporal region. The postoperative freedom from seizures in each case (follow‐up, 2 to 4 years) confirmed that HS was the primary epileptogenic process, and that the BFEDCs were incidental or an atypical secondary manifestation.

Conclusions: These cases illustrate the need for more extensive study of children with BFEDCs when medical intractability and seizure symptoms speak against a simple diagnosis of benign focal epilepsy of childhood. In addition, we observed that the BFEDCs in two of our children had an unusual bilateral occipitofrontal distribution, and we speculate that the coexistence of the BFEDCs in children with HS may not be an incidental finding.
Telephone‐induced Seizures: A New Type of Reflex Epilepsy
Authors: Michelucci Roberto , Gardella Elena , De Haan Gerrit‐Jan , Bisulli Francesca , Zaniboni Anna , Cantalupo Gaetano , Alberto Tassinari Carlo , Tinuper Paolo , Nobile Carlo , Nichelli Paolo , Kasteleijn‐Nolst Trenité Dorothée G. A.
Published: February 2004

Summary: Purpose:To report a new form of reflex epilepsy in which the seizures are repeatedly and exclusively triggered by answering the telephone.

Methods:Three patients with a history of telephone‐induced seizures were studied in detail by means of clinical, EEG, and neuroradiologic investigations. Intensive video‐EEG monitoring to record the reflex seizures also was performed in all cases.

Results:The patients (two men, one woman, aged 21 to 30 years) had the onset during early adulthood of complex partial and secondarily generalized seizures exclusively triggered by answering the telephone. The seizures were stereotyped, with subjective auditory or vertiginous auras and inability to speak or understand the spoken voices. In one patient, a telephone‐induced seizure arising from the dominant temporal lobe was recorded by means of video‐EEG technique. In the interictal EEGs, temporal abnormalities were detected in all cases. The patients had a normal neurologic examination and normal magnetic resonance imaging or computed tomography scans.

Conclusions:We suggest that telephone epilepsy is a previously unrecognized form of reflex epilepsy induced by a complex auditory stimulus involving the lateral temporal areas.
Patients with Temporoparietal Ictal Symptoms and Inferomesial EEG Do Not Benefit from Anterior Temporal Resection
Authors: Aghakhani Yahya , Rosati Anna , Dubeau François , Olivier André , Andermann Frederick
Published: February 2004

Summary:  Purpose: The role of posterior structural lesions leading to inadequate results after inferomesial temporal resection is well recognized. Here we present poor surgical outcome in six patients with nonlesional intractable epilepsy, well‐defined focal anterior and inferomesial temporal epileptic discharges, and posterior temporoparietal symptoms.

Methods: We reviewed patient data including scalp video‐EEG telemetry, intracranial EEG recording, magnetic resonance imaging (MRI) sequences (1.5 Tesla), and single‐photon emission computed tomography (SPECT) findings.

Results: Ictal onset was uni‐ or bilateral diffuse with late preponderance over one temporal, or centrotemporoparietal regions. Four patients had preresection intracranial EEG monitoring, which suggested an epileptogenic zone in the posterior temporal and inferior parietal area in two, in the temporal lobe in one, and was inconclusive in the remaining one, who showed late epileptiform activity in the temporal neocortex. A second intracranial implantation was performed in three of them after a first anterior temporal resection. This led to posterior temporal neocortical localization in two and posterior temporal–inferior parietal localization in one. Including subpial transection, these six patients had one to four operations each, but only limited improvement occurred as a result of surgery in this group of individuals.

Conclusions: We conclude that anterior and inferomesial interictal epileptiform temporal discharges and at times even intracranial EEG monitoring may be misleading. Anteromesial temporal resection is ineffective in patients with posterior temporoparietal clinical ictal features.
Autosomal Dominant Lateral Temporal Epilepsy: Two Families with Novel Mutations in the LGI1 Gene
Authors: Hedera Peter , Abou‐Khalil Bassel , Crunk Amy E. , Taylor Kelly A. , Haines Jonathan L. , Sutcliffe James S.
Published: February 2004

Summary:  Purpose: Mutations in the leucine rich, glioma inactivated gene (LGI1) were recently described in a small number of families with autosomal dominant lateral temporal epilepsy (ADLTE). ADLTE is characterized by partial seizures with symptoms suggestive of a lateral temporal onset, including frequent auditory aura. Here we report the results of clinical and genetic analyses of two newly identified families with ADTLE.

Methods: We identified two families whose seizure semiology was suggestive of ADLTE. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. The coding sequence of the LGI1 gene from affected subjects from both families was analyzed for evidence of mutation.

Results: Each patient had a history of partial seizures, often with secondary generalization earlier in the course. Auditory aura was reported by approximately two thirds of affected patients in each pedigree. Novel mutations in LGI1 were detected in both families. A heterozygous single‐nucleotide deletion at position 329 (del 329C) was detected in affected individuals from one family, whereas patients from the second family had a nonsynonymous variation, corresponding to C435G.

Conclusions: We identified two novel mutations in the LGI1 gene. The phenotype of these two families was similar to that of other kindreds with ADLTE, as auditory aura was absent in one third of affected individuals. Our results further support that LGI1 mutations should be considered in patients with a history of partial seizures if the semiology of seizures is consistent with the onset in the lateral temporal lobe.
Epilepsy Duration, Febrile Seizures, and Cerebral Glucose Metabolism
Authors: Theodore William H. , Kelley Kathey , Toczek Maria T. , Gaillard William D.
Published: February 2004

Summary:  Purpose: Studies using magnetic resonance imaging have shown that reduced hippocampal volume is associated with a history of febrile seizures, the duration of epilepsy, and the number of generalized tonic–clonic seizures. It is uncertain whether these factors have the same influence on functional as on structural measures of the integrity of the epileptogenic zone.

Methods: We used positron emission tomography (PET) with fluorine 18 2‐deoxyglucose to study 91 patients with temporal lobe seizure foci localized by ictal video‐EEG. PET was performed in the awake interictal resting state with ears plugged and eyes patched. We recorded surface EEG during injection (5 mCi) and the 30‐min uptake period. We used a standard template to analyze PET scans.

Results: A significant negative relation was found between the duration of epilepsy and hippocampal glucose metabolism ipsilateral to the epileptic focus. Patients with a history of either any febrile seizures, or complex, or prolonged febrile seizures, did not have greater hypometabolism ipsilateral to the epileptic focus than did patients without a febrile seizure history. We found no effect of generalized tonic–clonic seizure history.

Conclusions: Longer epilepsy duration is associated with greater hypometabolism, suggesting that epilepsy is a progressive disease.
Cost of Epilepsy in Patients Attending a Secondary‐level Hospital in India
Authors: Krishnan Anand , Sahariah Siraz‐ul Ameen , Kapoor Suresh Kumar
Published: February 2004

Summary:  The study objective was out to provide an estimate of cost of epilepsy in a secondary level hospital in northern India where a once a week epilepsy clinic is run. Cost data were based on existing information on costs of the hospital and market rates for drugs and investigations. Other necessary information was extracted from patient records for the year 2001. Both direct (consultation fees, cost of investigation, drugs and facility costs) and indirect (traveling and loss of productivity) were estimated. A 25% loss of productivity was assumed based on interviews with the epilepsy patients attending the clinic. There were a total of 184 patients attending the epilepsy clinic during the year 2001. The annual drug cost of epilepsy treatment using phenobarbitone was U.S.$11. The cost of drugs was in the ratio 1:2:3:4 for phenobarbitone, phenytoin, carbamazepine and sodium valproate. The average annual cost of outpatient treatment of epilepsy was found to be U.S.$47 per patient. The annual cost incurred in emergency and inpatient management was estimated at U.S.$810.50 and U.S.$168.30 for all the patients attending the secondary hospital during the year 2001. The total annual treatment cost for patients attending the hospital was U.S.$11,470. The annual productivity loss for the same patients was estimated at U.S.$20,475. Applying these to the estimated 5 million epilepsy patients in India, it comes to about 0.2% of the GNP of the country. As disease cost is much lower than productivity loss, epilepsy treatment is a worthwhile investment for the society. Treating epilepsy patients at primary level using phenobarbitone will increase the treatment coverage and reduce treatment costs. Simultaneous efforts must be made to bring the epilepsy patients on mainstream so as to reduce the productivity loss.
A Comparison of HMO Efficiencies as a Function of Provider Autonomy
Authors: Brockett Patrick L. , Chang Ray E. , Rousseau John J. , Semple John H. , Yang Chuanhou
Published: February 2004

Abstract

Current debates in the insurance and public policy literatures over health care financing and cost control measures continue to focus on managed care and HMOs. The lower utilization rates found in HMOs (compared to traditional fee‐for‐service indemnity plans) have generally been attributed to the organization's incentive to eliminate all unnecessary medical services. As a consequence HMOs are often considered to be a more efficient arrangement for delivering health care. However, it is important to make a distinction between utilization and efficiency (the ratio of outcomes to resources). Few studies have investigated the effect that HMO arrangements would have on the actual efficiency of health care delivery. Because greater control over provider autonomy appears to be a recurrent theme in the literature on reform, it is important to investigate the effects these restrictions have already had within the HMO market. In this article, the efficiencies of two major classes of HMO arrangements are compared using “game‐theoretic” data envelopment analysis (DEA) models. While other studies confirm that absolute costs to insurance firms and sponsoring companies are lowered using HMOs, our empirical findings suggest that, within this framework, efficiency generally becomes worse when provider autonomy is restricted. This should give new fuel to the insurance companies providing fee‐for‐service (FFS) indemnification plans in their marketplace contentions.
Why Are Managed Care Plans Less Expensive: Risk Selection, Utilization, or Reimbursement?
Authors: Polsky Daniel , Nicholson Sean
Published: February 2004

Abstract

This article develops a new method of decomposing the cost difference between HMO and non‐HMO plans into observed risk selection, unobserved risk selection, utilization differences, and differences in provider reimbursement rates. We implement this method using a large national sample of employer‐sponsored health insurance enrollees from the Community Tracking Study Household Survey. We find no evidence that HMO plans attract a disproportionate share of low‐risk enrollees; the US$188 difference between HMO and non‐HMO medical expenditures per enrollee can be explained by the relatively low provider reimbursement rates paid by HMO plans. This indicates there may be little need for employers to risk adjust insurance premiums or otherwise restrict employee choice of plan types.
The Effects of Uncertainty on the Demand for Health Insurance
Authors: Koç Çaḡatay
Published: February 2004

Abstract

This article analyzes the effects of uncertainty and increases in risk aversion on the demand for health insurance using a theoretical model that highlights the interdependence between insurance and health care demand decisions. Two types of uncertainty faced by the individuals are examined. The first one is the uncertainty in the consumer's pretreatment health and the second is the uncertainty surrounding the productivity of health care. Comparative statics results are reported indicating the impact on the demand for insurance of shifts in the distributions of pretreatment health and productivity of health care in the form of first‐order stochastic dominance, Rothschild–Stiglitz mean‐preserving spreads, and second‐order stochastic dominance. The demand for insurance increases in response to a Rothschild–Stiglitz increase in risk in the distribution of the pretreatment health provided that the health production function is in a special class and the price elasticity of health care is nondecreasing in the pretreatment health. Provided also that the demand for health care is own‐price inelastic, the same conclusion is obtained when the uncertainty is about the productivity of health care.
The Impact of the Health Insurance Market on Small Firm Employment
Authors: Kapur Kanika
Published: February 2004

Abstract

Small firms that offer health insurance to their employees may face variable premiums if they hire employees with high expected health costs. To avoid expensive premium variability, small firms may attempt to maintain a workforce with low expected health costs. This results in employment distortions. I examine the magnitude of these employment distortions using the 1987 National Medical Expenditure Survey and the 1996 Medical Expenditure Panel Survey. Based on the underwriting behavior of insurance companies in 1988, I classify medical conditions into three categories: conditions that led to denial of coverage; conditions that led to exclusion restrictions; and, conditions that led to higher premiums. In 1987, I find that insured small firms were less likely to employ workers with families that had conditions that led to higher premiums than insured large firms. However, in 1996, possibly due to the passage of small group health insurance reforms that restrict insurers' ability to exclude or deny coverage, insured small firms were less likely to employ workers with denial conditions compared to insured large firms. These results suggest that the pattern of employment distortions in insured small firms is consistent with the evolving small group health insurance market.
An Analysis of the Effect of Tax Policy on Health Insurance Purchases by Risk Group
Authors: Ketsche Patricia G.
Published: February 2004

Abstract

There is an extensive body of literature dealing with the welfare loss associated with generous levels of health insurance as a function of the tax subsidy. The theoretical discussion in this study considers the effect of the tax subsidy on pooling within plans, and suggests the hypotheses that the tax subsidy will have a disproportionately positive effect on the likelihood that a high‐risk worker will be eligible for and participate in employment‐based coverage, while the effect of the tax subsidy on plan generosity will be greatest for low‐risk employees. If coverage of high‐risk individuals enhances social welfare, this result may offset, at least in part, the welfare loss associated with generous plans. Data from the 1987 National Medical Expenditure Survey are used to test these hypotheses. The results provide evidence that the subsidy works to expand risk pools in the employment‐based health insurance market.
Pure Versus Mutual Health Insurance: Evidence From Swedish Historical Data
Authors: Nekby Lena
Published: February 2004

Abstract

Using data from voluntary Swedish health insurance societies 1902‐1910, this article analyzes the coexistence of pure and mutual insurance societies where pure societies are characterized by charging ex ante premiums only while mutuals in addition charge ex post assessments. On average, mutual insurance societies are found to be larger and to offer greater insurance coverage per member. Pure insurance societies have, on average, higher insurance coverage per day, greater mean levels of moral hazard controls, a higher mean number of policy categories, and greater longevity.
Production Efficiency in the Austrian Insurance Industry: A Bayesian Examination
Authors: Ennsfellner Karl C. , Lewis Danielle , Anderson Randy I.
Published: February 2004

Abstract

This paper examines the developments in the production efficiency of the Austrian insurance market for the period 1994‐1999 using firm‐specific data on life/health and non‐life insurers obtained from the Austrian insurance regulatory authority. The article uses a Bayesian stochastic frontier to obtain aggregate and firm‐specific estimates of production efficiency across insurer types and time. The study provides strong evidence that the process of deregulation had positive effects on the production efficiency of Austrian insurers. The life/health and non‐life firms showed similar patterns of development in that they were less efficient during the years 1994‐1996 and significantly more efficient in 1997‐1999. If the Austrian experience is representative, similar benefits from deregulation may be expected for the Central and Eastern European countries that prepare for the accession to the European Union.
A Quantitative Risk Assessment of Waterborne Cryptosporidiosis in France Using Second‐Order Monte Carlo Simulation
Authors: Pouillot Régis , Beaudeau Pascal , Denis Jean‐Baptiste , Derouin Francis ,   AFSSA Cryptosporidium Study Group
Published: February 2004

A pragmatic quantitative risk assessment (QRA) of the risks of waterborne Cryptosporidium parvum infection and cryptosporidiosis in immunocompetent and immunodeficient French populations is proposed. The model takes into account French specificities such as the French technique for oocyst enumeration performance and tap water consumption. The proportion of infective oocysts is based on literature review and expert knowledge. The probability of infection for a given number of ingested viable oocysts is modeled using the exponential dose‐response model applied on published data from experimental infections in immunocompetent human volunteers challenged with the IOWA strain. Second‐order Monte Carlo simulations are used to characterize the uncertainty and variability of the risk estimates. Daily risk of infection and illness for the immunocompetent and the immunodeficient populations are estimated according to the number of oocysts observed in a single storage reservoir water sample. As an example, the mean daily risk of infection in the immunocompetent population is estimated to be 1.08 × 10−4 (95% confidence interval: [0.20 × 10−4; 6.83 × 10−4]) when five oocysts are observed in a 100 L storage reservoir water sample. Annual risks of infection and disease are estimated from a set of oocyst enumeration results from distributed water samples, assuming a negative binomial distribution of day‐to‐day contamination variation. The model and various assumptions used in the model are fully explained and discussed. While caveats of this model are well recognized, this pragmatic QRA could represent a useful tool for the French Food Safety Agency (AFSSA) to define recommendations in case of water resource contamination by C. parvum whose infectivity is comparable to the IOWA strain.
Combining Food Frequency and Survey Data to Quantify Long‐Term Dietary Exposure: A Methyl Mercury Case Study
Authors: Tran Nga L. , Barraj Leila , Smith Kim , Javier Annabelle , Burke Thomas A.
Published: February 2004

Twenty‐four‐hour recall data from the Continuing Survey of Food Intake by Individuals (CSFII) are frequently used to estimate dietary exposure for risk assessment. Food frequency questionnaires are traditional instruments of epidemiological research; however, their application in dietary exposure and risk assessment has been limited. This article presents a probabilistic method of bridging the National Health and Nutrition Examination Survey (NHANES) food frequency and the CSFII data to estimate longitudinal (usual) intake, using a case study of seafood mercury exposures for two population subgroups (females 16 to 49 years and children 1 to 5 years). Two hundred forty‐nine CSFII food codes were mapped into 28 NHANES fish/shellfish categories. FDA and state/local seafood mercury data were used. A uniform distribution with minimum and maximum blood‐diet ratios of 0.66 to 1.07 was assumed. A probabilistic assessment was conducted to estimate distributions of individual 30‐day average daily fish/shellfish intakes, methyl mercury exposure, and blood levels. The upper percentile estimates of fish and shellfish intakes based on the 30‐day daily averages were lower than those based on two‐ and three‐day daily averages. These results support previous findings that distributions of “usual” intakes based on a small number of consumption days provide overestimates in the upper percentiles. About 10% of the females (16 to 49 years) and children (1 to 5 years) may be exposed to mercury levels above the EPA's RfD. The predicted 75th and 90th percentile blood mercury levels for the females in the 16‐to‐49‐year group were similar to those reported by NHANES. The predicted 90th percentile blood mercury levels for children in the 1‐to‐5‐year subgroup was similar to NHANES and the 75th percentile estimates were slightly above the NHANES.
A Comparison of Three Methods for Calculating Confidence Intervals for the Benchmark Dose
Authors: Moerbeek Mirjam , Piersma Aldert H. , Slob Wout
Published: February 2004

Various methods exist to calculate confidence intervals for the benchmark dose in risk analysis. This study compares the performance of three such methods in fitting nonlinear dose‐response models: the delta method, the likelihood‐ratio method, and the bootstrap method. A data set from a developmental toxicity test with continuous, ordinal, and quantal dose‐response data is used for the comparison of these methods. Nonlinear dose‐response models, with various shapes, were fitted to these data. The results indicate that a few thousand runs are generally needed to get stable confidence limits when using the bootstrap method. Further, the bootstrap and the likelihood‐ratio method were found to give fairly similar results. The delta method, however, resulted in some cases in different (usually narrower) intervals, and appears unreliable for nonlinear dose‐response models. Since the bootstrap method is more time consuming than the likelihood‐ratio method, the latter is more attractive for routine dose‐response analysis. In the context of a probabilistic risk assessment the bootstrap method has the advantage that it directly links to Monte Carlo analysis.
Dose‐Response Model for 13 Strains of Salmonella
Authors: Oscar Thomas
Published: February 2004

Data from a human feeding trial with healthy men were used to develop a dose‐response model for 13 strains of Salmonella and to determine the effects of strain variation on the shape of the dose‐response curve. Dose‐response data for individual strains were fit to a three‐phase linear model to determine minimum, median, and maximum illness doses, which were used to define Pert distributions in a computer simulation model. Pert distributions for illness dose of individual strains were combined in an Excel spreadsheet using a discrete distribution to model strain prevalence. In addition, a discrete distribution was used to model dose groups and thus create a model that simulated human feeding trials. During simulation of the model with @Risk, an illness dose and a dose consumed were randomly assigned to each consumption event in the simulated feeding trial and if the illness dose was greater than the dose consumed then the model predicted no illness, otherwise the model predicted that an illness would occur. To verify the dose‐response model predictions, the original feeding trial was simulated. The dose‐response model predicted a median of 69 (range of 43–101) illnesses compared to 74 in the original trial. Thus, its predictions were in agreement with the data used to develop it. However, predictions of the model are only valid for eggnog, healthy men, and the strains and doses of Salmonella used to develop it. When multiple strains of Salmonella were simulated together, the predicted dose‐response curves were irregular in shape. Thus, the sigmoid shape of dose‐response curves in feeding trials with one strain of Salmonella may not accurately reflect dose response in naturally contaminated food where multiple strains may be present.
Children's Exposure to Arsenic from CCA‐Treated Wooden Decks and Playground Structures
Authors: Hemond Harold F. , Solo‐Gabriele Helena M.
Published: February 2004

CCA‐treated wood is widely used in the fabrication of outdoor decks and playground equipment. Because arsenic can be removed from the surface of CCA‐treated wood both by physical contact and by leaching, it is important to determine whether children who play on such structures may ingest arsenic in quantities sufficient to be of public health concern. Based on a review of existing studies, it is estimated that arsenic doses in amounts of tens of micrograms per day may be incurred by children having realistic levels of exposure to CCA‐treated decks and playground structures. The most important exposure pathway appears to be oral ingestion of arsenic that is first dislodged from the wood by direct hand contact, then transferred to the mouth by children's hand‐to‐mouth activity. The next most important pathway appears to be dermal absorption of arsenic, while ingestion of soil that has become contaminated by leaching from CCA‐treated structures appears to be of lesser importance, except possibly in the case of children with pica. Considerable uncertainty, however, is associated with quantitative estimates of children's arsenic exposure from CCA‐treated wood. Priorities for refining estimates of arsenic dose include detailed studies of the hand‐to‐mouth transfer of arsenic, studies of the dermal and gastrointestinal absorption of dislodgeable arsenic, and studies in which doses of arsenic to children playing in contact with CCA‐treated wood are directly determined by measurement of arsenic in their urine, hair, and nails.
A Parametric Model for Detecting Hormetic Effects in Developmental Toxicity Studies
Authors: Hunt Daniel L. , Bowman Dale
Published: February 2004

Hormetic effects have been observed at low exposure levels based on the dose‐response pattern of data from developmental toxicity studies. This indicates that there might actually be a reduced risk of exhibiting toxic effects at low exposure levels. Hormesis implies the existence of a threshold dose level and there are dose‐response models that include parameters that account for the threshold. We propose a function that introduces a parameter to account for hormesis. This function is a subset of the set of all functions that could represent a hormetic dose‐response relationship at low exposure levels to toxic agents. We characterize the overall dose‐response relationship with a piecewise function that consists of a hormetic u‐shape curve at low dose levels and a logistic curve at high dose levels. We apply our model to a data set from an experiment conducted at the National Toxicology Program (NTP). We also use the beta‐binomial distribution to model the litter response data. It can be seen by observing the structure of these data that current experimental designs for developmental studies employ a limited number of dose groups. These designs may not be satisfactory when the goal is to illustrate the existence of hormesis. In particular, increasing the number of low‐level doses improves the power for detecting hormetic effects. Therefore, we also provide the results of simulations that were done to characterize the power of current designs in detecting hormesis and to demonstrate how this power can be improved upon by altering these designs with the addition of only a few low exposure levels.
Estimating Contaminant Dose for Intermittent Dermal Contact: Model Development, Testing, and Application
Authors: Riley W. J. , McKone T. E. , Cohen Hubal E. A.
Published: February 2004

Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure scenarios, skin surface loading and unloading rates, and contaminant movement through the epidermis. In this article we (1) develop and test a finite‐difference model of contaminant transport through the epidermis; (2) develop archetypal exposure scenarios based on behavioral data to estimate characteristic loading and unloading rates; and (3) quantify 24‐hour accumulation below the epidermis by applying a Monte Carlo simulation of these archetypal exposure scenarios. The numerical model, called Transient Transport through the epiDERMis (TTDERM), allows us to account for variable exposure times and time between exposures, temporal and spatial variations in skin and compound properties, and uncertainty in model parameters. Using TTDERM we investigate the use of a macro‐activity parameter (cumulative contact time) for predicting daily (24‐hour) integrated uptake of pesticides during complex exposure scenarios. For characteristic child behaviors and hand loading and unloading rates, we find that a power law represents the relationship between cumulative contact time and cumulative mass transport through the skin. With almost no loss of reliability, this simple relationship can be used in place of the more complex micro‐activity simulations that require activity data on one‐ to five‐minute intervals. The methods developed in this study can be used to guide dermal exposure model refinements and exposure measurement study design.
Earthquake Beliefs and Adoption of Seismic Hazard Adjustments
Authors: Whitney David J. , Lindell Michael K. , Nguyen Hannah‐Hanh D.
Published: February 2004

This study investigated the prevalence of both accurate and erroneous earthquake‐related beliefs among a sample of Southern California college students and the relationship between their endorsement of earthquake beliefs and adoption of seismic hazard adjustments. In addition, the study examined the effects of an experimental earthquake education program and the impact of need for cognition on this program. The data revealed a significant degree of agreement with earthquake myths, a generally low level of correlation between earthquake beliefs and the level of hazard adjustments, and a significant effect of hazard information on the endorsement of accurate earthquake beliefs and increases in hazard adjustment. Compared with the “Earthquake Facts (Only)” format, an “Earthquake Myths versus Facts” format was slightly more useful for dispelling erroneous beliefs. Further, there was a tendency for those who were high in need for cognition to have higher levels of hazard adjustment. Finally, there was weak support for the hypothesis that those who were low in need for cognition would develop more accurate earthquake beliefs and higher levels of hazard adjustment in the “Earthquake Myths versus Facts” information condition.
Varying Risk Comparison Elements: Effects on Public Reactions
Authors: Johnson Branden B.
Published: February 2004

Expanding a limited empirical base on effects of risk comparisons, a pilot experiment explored how varying elements of such comparisons might influence public response. The scenario used was a hypothetical trial of an asbestos‐installing firm for putting students and staff at a junior high school at “unreasonable risk,” first used by Slovic et al. (1990). Study participants played the role of jurors in the trial, asked to rate the risk, the firm's guilt, whether it should be made liable for future health effects, whether the school should be occupied in its current condition, and whether the asbestos should be removed at a cost of $3 million. Opportunity samples of New Jersey residents (n= 309) received information intended to vary four comparison attributes: number of dimensions of comparison; single versus multiple ways of expressing mortality; a narrative to explain and justify the risk comparison; and the hypothetical role of the participant (juror vs. parent). The dependent variable was a hazard scale constructed from four of the five postcomparison judgments. ANOVA found format variations swamped in their effect by concern about asbestos, with the absence of a narrative and the parental role being the only attributes that increased negative risk reactions. Multiple regression analyses found that multidimensionality, narrative, role, and the presence of any risk comparison at all had significant effects when these (plus death formats) were the only independent variables. However, only multidimensionality (which increased negative reactions) retained significance when asbestos concern, risk beliefs (no safe level of exposure to a carcinogen; any exposure leads to cancer), and demographic variables were added to the analysis. Concern and risk beliefs alone explained 33% of variance in hazard scores; adding demographics and risk comparison variables only raised explained variance to 36% (having children at home and being exposed to multidimensional risk comparisons raised scores; age and income lowered them). The results underline the potentially small effect of risk comparison information on risk views (at least between subjects), but offer some insight into aspects of message design left unexplored in empirical literature to date.
Discrimination, Vulnerability, and Justice in the Face of Risk
Authors: Satterfield Terre A. , Mertz C. K. , Slovic Paul
Published: February 2004

Recent research finds that perceived risk is closely associated with race and gender. In surveys of the American public a subset of white males stand out for their uniformly low perceptions of environmental health risks, while most nonwhite and nonmale respondents reveal higher perceived risk. Such findings have been attributed to the advantageous position of white males in American social life. This article explores the linked possibility that this demographic pattern is driven not simply by the social advantages or disadvantages embodied in race or gender, but by the subjective experience of vulnerability and by sociopolitical evaluations pertaining to environmental injustice. Indices of environmental (in)justice and social vulnerability were developed as part of a U.S. National Risk Survey (n= 1,192) in order to examine their effect on perceived risk. It was found that those who regarded themselves as vulnerable and supported belief statements consistent with the environmental justice thesis offered higher risk ratings across a range of hazards. Multivariate analysis indicates that our measures of vulnerability and environmental (in)justice predict perceived risk but do not account for all of the effects of race and gender. The article closes with a discussion of the implications of these findings for further work on vulnerability and risk, risk communication, and risk management practices generally.