bluuebunny/crossref_metadata_2025 huggingface dataset:
Spirituality and Subjective Religiosity Among African Americans, Caribbean Blacks, and Non‐Hispanic Whites
Authors: CHATTERS LINDA M. , TAYLOR ROBERT JOSEPH , BULLARD KAI M. , JACKSON JAMES S.
Published: November 2008

Patterns and correlates of self‐perceptions of spirituality and subjective religiosity are examined using data from the National Survey of American Life, a nationally representative study of African Americans, Caribbean blacks, and non‐Hispanic whites. Demographic and denominational correlates of patterns of subjective religiosity and spirituality (i.e., religious only, spiritual only, both religious/spiritual, and neither religious/spiritual) are examined. In addition, the study of African Americans and Caribbean blacks permits the investigation of possible ethnic variation in the meaning and conceptual significance of these constructs within the U.S. black population. African Americans and Caribbean blacks are more likely than non‐Hispanic whites to indicate that they are “both religious and spiritual” and less likely to indicate that they are “spiritual only” or “neither spiritual nor religious.” Demographic and denominational differences in the patterns of spirituality and subjective religiosity are also indicated. Study findings are discussed in relation to prior research in this field and conceptual and methodological issues deserving further study are noted.
“Out of the Broom Closet”: The Social Ecology of American Wicca
Authors: JENSEN GARY F. , THOMPSON ASHLEY
Published: November 2008

The fastest growing form of religious identification, spirituality, or “new” religious movement in American society over the last decade is Wicca and related forms of “Neo‐Paganism.” However, with no national organization and minimal local organization, little is known about its distribution across a privatized religious landscape nor about the features of state social and cultural environments that are receptive or contrary to its spread. This study uses Internet data to create estimates of the comparative strength of Wiccan‐Pagan identification across the 50 states and conducts multivariate analyses of the ability of variables suggested in prior research to explain its distribution. Not only are the findings consistent with expectations, but differences in correlates of Wicca using the Internet data in contrast to existing measures of “New Age” spirituality highlight the empirical importance of maintaining distinctions between the two.
Reproductive success of house sparrows along an urban gradient
Authors: Peach W. J. , Vincent K. E. , Fowler J. A. , Grice P. V.
Published: November 2008

Recent large declines in house sparrow Passer domesticus L. populations in many European towns and cities have generated much speculation as to possible environmental causes, although empirical insights have been lacking. We measured reproductive success in a declining house sparrow population along an urbanization gradient in Leicester, England, and used mixed models to identify correlates of nesting success. A stochastic simulation approach was developed to estimate annual reproductive success when the number of breeding attempts was unknown, and to assess the sensitivity of reproductive success to variation in different environmental factors. During 2 out of 3 years, reproductive output was lower than the predicted threshold required for population stability. Years of inadequate reproduction were characterized by lower chick survival and body mass at fledging (a predictor of post‐fledging survival). Factors associated with reduced reproductive output included low ambient temperatures, extremes of rainfall, high levels of vegetable material in the diet (all affecting chick survival and body mass), low aphid densities (an important component of chick diet) and high concentrations of air pollution from traffic (affecting chick body mass). Reproductive failure linked to inadequate invertebrate availability provides a plausible demographic mechanism accounting for declines in urban–suburban house sparrow populations. Increased traffic volume and vegetation removal are candidate causal factors in these declines although the mechanism underlying the former is unclear. Increasing densities of key invertebrate prey away from major roads should be an objective of conservation management aimed at urban–suburban house sparrows. This study illustrates the utility of mixed models for the analysis of individual sibling survival and of stochastic simulation for modelling reproductive success in multi‐brooded animals.
The Brief Child and Family Phone Interview (BCFPI): 2. Usefulness in screening for child and adolescent psychopatholog
Authors: Boyle Michael H. , Cunningham Charles E. , Georgiades Katholiki , Cullen John , Racine Yvonne , Pettingill Peter
Published: November 2008

Background:  This study examines the use of the Brief Child and Family Phone Interview (BCFPI) to screen for childhood psychiatric disorder based on Diagnostic Interview Schedule for Children Version IV (DISC‐IV) classifications of attention‐deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), separation anxiety (SAD), generalized anxiety (GAD) and major depression (MDD).

Methods:  Data for analysis come from a sample of 399 children and adolescents aged 5–17 years old referred to child mental health outpatient services in three Ontario cities. Mothers were administered the BCFPI on three occasions: baseline, 2 and 13 months; and the DISC‐IV on two occasions: 1 and 12 months.

Results:  Based on kappa, test–retest reliability for disorders classified by the BCFPI exceeded .50 for all conditions except MDD (.45). In receiver operating characteristic (ROC) analysis, area‐under‐the‐curve (AUC) estimates for BCFPI scale score associations with DISC‐IV classifications of disorder exceeded .80 for CD, ODD, ADHD and SAD; and were lower for GAD (.76) and MDD (.75). In stratified analyses, there were no statistically significant differences in AUC estimates for boys versus girls and 5 to 11 versus 12 to 17‐year‐olds.

Conclusions:  Classifications of childhood disorder derived from the BCFPI provided a reasonable approximation to disorders classified by the DISC‐IV administered by lay interviewers.
Telling tales: using storytelling to explore and model critical reflective practice in integrated children's services
Authors: Haines CQSW, CASS, BSc Carole , Livesley RSCN, RGN, BSc, MA Joan
Published: November 2008

Realizing the vision for integrated children's services will rely on effective collaboration and joined‐up working across professional boundaries. One way of achieving this is to open up professional practice to the scrutiny of other professional groups in order that shared understanding can be developed. This brief article describes how we use story telling to model critical reflection and to invite students to reflect on their own constructions of their own and other professional groups. The story telling takes place during one timetabled session as part of a planned interprofessional learning module for students of nursing and social work. The authors, a lecturer in social work and a lecturer in children's nursing, had, by chance, been co‐located in the same office. Working together led to many conversations and a realization of how we would often use the same words to make sense of our practice with children and families, but sometimes mean different things. The idea for the story‐telling session was developed from these conversations.

The story, ‘Telling tales’ (see box 1), focuses on the real‐life reflections of a children's nurse who worked with a young boy. He had been admitted to hospital and separated from his mother for a period of 1 week. The story is told to the students using the original words of the nurse. In this study, we describe the background to the initiative, how we use the story and what happens when we do. We contend that story telling is a powerful technique for opening up professional practice to the scrutiny of other professional groups. It also provides an effective vehicle to invite the students to critically challenge what they hold dear, just in case they are wrong.
Reforming the children and young people's workforce: a higher education response
Authors: Oliver Billie
Published: November 2008

The Every Child Matters change agenda is leading to the creation of new services and new working practices across the children and young people's sectors. These new configurations are leading to the development of new roles that do not necessarily fit with existing, traditional professional qualifications. This paper outlines the response of one university to this policy agenda. The experience of inter‐disciplinary collaboration and interprofessional curriculum development has mirrored many of the challenges facing colleagues in practice settings. In reflecting on these challenges, this study highlights some of the key issues facing higher education providers in developing an appropriate educational response. The study identifies the need for collaborative and strategic partnership between higher education and practice colleagues in order to prepare a future workforce. It further identifies the desirability of a champion with the capacity and determination to keep the agenda from getting lost within all the other uni‐disciplinary agendas that operate within universities.
Learning in and for interagency working: making links between practice development and structured reflection
Authors: Leadbetter Jane
Published: November 2008

This article describes a large national research project that followed a range of multi‐agency teams, within newly formed Children's Services in England, as they began to change and develop as a result of national and local policy changes. As the title suggests, the focus of the research was to observe the learning that was taking place and to offer approaches to facilitate the group learning. The approach is novel in that it employed a specific theoretical approach to the work; namely, the use of cultural–historical activity theory (CHAT), to analyse what was happening in the research sites and to structure and facilitate the intervention workshops. The findings reflect what was happening within teams, at individual, group and systemic levels. They also add to the body of knowledge that is accumulating in the application of activity theoretical approaches to work‐place learning. Some of the findings are expanded to offer suggestions for similar teams to consider as they make transitions within ever‐changing, expanding Children's Services. These include recommendations for professionals regarding the child and the wider context, aspects of professional role and focus of work, developing new tools, reconsidering existing rules, and examining values and pedagogic approaches in the work‐place.
Creating interprofessional learning capacity in children's centres – description and evaluation of a pilot project
Authors: McCombe Jane , Develin Deborah , Mallik Maggie
Published: November 2008

Nationally, the promotion of interprofessional learning (IPL) at all levels is a key UK Government strategy aimed at improving communication, collaborative working and enhancing quality care for all service users. The development of interagency working through the provision of services for pre‐school children and their families within children's centres provides an ideal environment to promote interprofessional learning for pre‐registration health and social care students. A partnership project was established to develop new interprofessional practice learning placements for students completing social work and child branch nursing courses within two health and social care communities in a midland county and city in England.

Following information on the aims and objectives of the project, children's centres opted in to participate. The Common Learning Programme North East Model for IPL was adopted as a template for managing the variability in numbers and timings for student placements. Workshops were provided to prepare IPL facilitators; students attended workshops and completed an IPL workbook as part of their learning experience. A total of 14 children's centres participated over the 2 years of the project. An action research framework was used to underpin the collection of evaluation data through questionnaires, telephone interviews and focus groups. All stakeholders were involved in workshop events to action plan for improvements following feedback from evaluations.

All participating centres remained positive and encouraged other centres to participate. Problem areas highlighted and dealt with included the logistics involved in timing student placements; development and use of the IPL workbook; and ensuring enough IPL facilitators. A key factor contributing to the success of Creating Interprofessional Learning Capacity in Children's Centres has been effective partnership working with stakeholders from the higher education institutions, local authorities and the National Health Service. The benefits of IPL in providing students with an opportunity to develop into effective collaborative practitioners was recognised by those involved and resulted in a high level of commitment over the 2 years. Challenges remain and sustainability will always be an issue but gaining the ongoing commitment of all stakeholders within the children's centres themselves has been a key factor in the success of the project.
Exploring young people's participation in interprofessional education, taking a children's rights approach
Authors: Bennett Alison , Race Tracey
Published: November 2008

The Children, Young People and Families module was developed at Leeds Metropolitan University, UK in 2004. The module is jointly taught to community health and social work students with the active involvement of a Barnardo's Young People's Group. This module was developed in direct response to the challenges of the UK Every Child Matters policy agenda highlighting the importance of partnership and participation as the bedrock of effective practice in integrated children's services. For the writers, a commitment to the value base of social work means that it is not enough to lecture about child‐centred practice, children's rights and the importance of participation, without modelling these principles in our practice as educators. This article outlines key aspects of the module and its delivery, including the authors’ learning from partnership work with the Young People's Group. The work is evaluated drawing on student feedback and findings from an evaluation exercise carried out with the young people.
Impact of Public Reporting on Unreported Quality of Care
Authors: Werner Rachel M. , Konetzka R. Tamara , Kruse Gregory B.
Published: November 2008

Objective. The impact of quality improvement incentives on nontargeted care is unknown and some have expressed concern that such incentives may be harmful to nontargeted areas of care. Our objective is to examine the effect of publicly reporting quality information on unreported quality of care.

Data Sources/Study Setting. The nursing home Minimum Data Set from 1999 to 2005 on all postacute care admissions.

Study Design. We studied 13,683 skilled nursing facilities and examined how unreported aspects of clinical care changed in response to changes in reported care after public reporting was initiated by the Centers for Medicare and Medicaid Services on their website, Nursing Home Compare, in 2002.

Principal Findings. We find that overall both unreported and reported care improved following the launch of public reporting. Improvements in unreported care were particularly large among facilities with high scores or that significantly improved on reported measures, whereas low‐scoring facilities experienced no change or worsening of their unreported quality of care.

Conclusions. Public reporting in the setting of postacute care had mixed effects on areas without public reporting, improving in high‐ranking facilities, but worsening in low‐ranking facilities. While the benefits of public reporting may extend beyond areas that are being directly measured, these initiatives may also widen the gap between high‐ and low‐quality facilities.
Method to Develop Health Care Peer Groups for Quality and Financial Comparisons Across Hospitals
Authors: Byrne Margaret M. , Daw Christina N. , Nelson Harlan A. , Urech Tracy H. , Pietz Kenneth , Petersen Laura A.
Published: November 2008

Objective. To develop and explore the characteristics of a novel “nearest neighbor” methodology for creating peer groups for health care facilities.

Data Sources. Data were obtained from the Department of Veterans Affairs (VA) databases.

Statistical Methods and Findings. Peer groups are developed by first calculating the multidimensional Euclidean distance between each of 133 VA medical centers based on 16 facility characteristics. Each medical center then serves as the center for its own peer group, and the nearest neighbor facilities in terms of Euclidean distance comprise the peer facilities. We explore the attributes and characteristics of the nearest neighbor peer groupings. In addition, we construct standard cluster analysis‐derived peer groups and compare the characteristics of groupings from the two methodologies.

Conclusions. The novel peer group methodology presented here results in groups where each medical center is at the center of its own peer group. Possible advantages over other peer group methodologies are that facilities are never on the “edge” of a group and group size—and thus group dispersion—is determined by the researcher. Peer groups with these characteristics may be more appealing to some researchers and administrators than standard cluster analysis and may thus strengthen organizational buy‐in for financial and quality comparisons.
Variation in Drug Prices at Pharmacies: Are Prices Higher in Poorer Areas?
Authors: Gellad Walid F. , Choudhry Niteesh K. , Friedberg Mark W. , Brookhart M. Alan , Haas Jennifer S. , Shrank William H.
Published: November 2008

Objective. To determine whether retail prices for prescription drugs are higher in poorer areas.

Data Sources. The MyFloridarx.com website, which provides retail prescription prices at Florida pharmacies, and median ZIP code income from the 2000 Census.

Study Design. We compared mean pharmacy prices for each of the four study drugs across ZIP code income groups. Pharmacies were classified as either chain pharmacies or independent pharmacies.

Data Collection. Prices were downloaded in November 2006.

Principal Findings. Across the four study drugs, mean prices were highest in the poorest ZIP codes: 9 percent above the statewide average. Independent pharmacies in the poorest ZIP codes charged the highest mean prices.

Conclusions. Retail prescription prices appear to be higher in poorer ZIP codes of Florida.
Relationship of Safety Climate and Safety Performance in Hospitals
Authors: Singer Sara , Lin Shoutzu , Falwell Alyson , Gaba David , Baker Laurence
Published: November 2008

Objective. To examine the relationship between measures of hospital safety climate and hospital performance on selected Patient Safety Indicators (PSIs).

Data Sources. Primary data from a 2004 survey of hospital personnel. Secondary data from the 2005 Medicare Provider Analysis and Review File and 2004 American Hospital Association's Annual Survey of Hospitals.

Study Design. A cross‐sectional study of 91 hospitals.

Data Collection. Negative binomial regressions used an unweighted, risk‐adjusted PSI composite as dependent variable and safety climate scores and controls as independent variables. Some specifications included interpersonal, work unit, and organizational safety climate dimensions. Others included separate measures for senior managers and frontline personnel's safety climate perceptions.

Principal Findings. Hospitals with better safety climate overall had lower relative incidence of PSIs, as did hospitals with better scores on safety climate dimensions measuring interpersonal beliefs regarding shame and blame. Frontline personnel's perceptions of better safety climate predicted lower risk of experiencing PSIs, but senior manager perceptions did not.

Conclusions. The results link hospital safety climate to indicators of potential safety events. Some aspects of safety climate are more closely related to safety events than others. Perceptions about safety climate among some groups, such as frontline staff, are more closely related than perceptions in other groups.
Anesthesia Provider Model, Hospital Resources, and Maternal Outcomes
Authors: Needleman Jack , Minnick Ann F.
Published: November 2008

Objective. Determine the ability of anesthesia provider model and hospital resources to explain maternal outcome variation.

Data Source/Study Setting. 1,141,641 obstetrical patients from 369 hospitals that reported at least one live birth in 2002 in six representative states.

Study Design. Logistic regression of death, anesthesia complication, nonanesthesia maternal complication, and obstetrical trauma for all patients and those having cesarean deliveries on anesthesia provider model, obstetrical and anesthesia, and patient variables.

Data Collection/Extraction Methods. Data was assembled from information given by hospitals to state agencies and from a 2004 survey of obstetrical organization resources.

Principal Findings. Anesthesia complication rates in anesthesiologist‐only hospitals were 0.27 percent compared with 0.23 percent in certified registered nurse anesthetist (CRNA) only hospitals. Rates among other provider models varied from 0.24 to 0.37 percent with none statistically different from the anesthesiologist‐only hospitals. A similar pattern was observed for rates of other outcomes. Multivariate analysis found no systematic differences between hospitals with anesthesiologist‐only models and models using CRNAs. There was no consistent pattern of association of other hospital or patient characteristics with outcomes.

Conclusion. Hospitals that use only CRNAs, or a combination of CRNAs and anesthesiologists, do not have systematically poorer maternal outcomes compared with hospitals using anesthesiologist‐only models.
Bilateral frontoparietal polymicrogyria, Lennox‐Gastaut syndrome, and GPR56 gene mutations
Authors: Parrini Elena , Ferrari Anna Rita , Dorn Thomas , Walsh Christopher A. , Guerrini Renzo
Published: November 2008

Purpose:  Bilateral frontoparietal polymicrogyria (BFPP) has been reported in sporadic patients and in recessive pedigrees. Eleven mutations in GPR56, a gene encoding an evolutionarily dynamic G‐protein–coupled receptor, have been identified in 29 patients from 18 families. The clinical features of BFPP include severe mental retardation, motor and language impairment, and epilepsy. No detailed description of the epilepsy is available for the patients reported to date. We report three consanguineous families in which four affected individuals with BFPP and GPR56 mutations had Lennox‐Gastaut syndrome.

Methods:  Family studies, brain magnetic resonance imaging (MRI), electroencephalography (EEG)‐video recordings, and mutation analysis.

Results:  In Family 1, with one affected proband, we found an R565W change in the second extracellular loop of GPR56, involving a highly conserved aminoacidic residue. In Family 2, with one affected proband, we found an R79X change affecting the protein N‐terminus and predicted to cause a premature truncation with loss of the G‐protein–coupled receptor proteolytic site. In family 3, with two affected siblings, we found an R33P substitution in the protein N‐terminus, involving a highly conserved aminoacidic residue. Epilepsy, present in all four patients, had started between ages 1 and 8 years, with infantile spasms in one patient and with de novo Lennox‐Gastaut syndrome in the remaining three. All patients had Lennox‐Gastaut syndrome when last observed, at ages 13 to 32 years.

Discussion:  Several genes, when mutated, can cause malformations of cortical development that have been associated with the Lennox‐Gastaut syndrome. BFPP caused by GPR56 mutations represents an additional, although rare, genetically determined cause of Lennox‐Gastaut syndrome.
History of the ketogenic diet
Authors: Wheless James W.
Published: November 2008

Summary

Fasting and other dietary regimens have been used to treat epilepsy since at least 500 BC. To mimic the metabolism of fasting, the ketogenic diet (KD) was introduced by modern physicians as a treatment for epilepsy in the 1920s. For two decades this therapy was widely used, but with the modern era of antiepileptic drug treatment its use declined dramatically. By the end of the twentieth century this therapy was available in only a small number of children's hospitals. Over the past 15 years, there has been an explosion in the use, and scientific interest in the KD. This review traces the history of one of the most effective treatments for childhood epilepsy.
The ketogenic diet—update on recent clinical trials
Authors: Cross J. Helen , Neal Elizabeth G.
Published: November 2008

Summary

The ketogenic diet (KD) has been used in the treatment of epilepsy for almost 100 years. Several cohort studies have emphasized its possible benefit, although use became less at the introduction of anticonvulsant medication. However, the KD has regained recognition over the past 15 years. Resources remain scarce and its availability for children may be limited. One argument has been the lack of evidence from suitably designed trials. Systematic reviews and meta‐analyses have revealed that studies are limited to class 3 and 4 data. A recently published randomized controlled trial has shown that the benefit of the KD is equivalent to any of the new anticonvulsant medications, emphasizing the need for more resources to ensure greater diet availability.
International consensus statement on clinical implementation of the ketogenic diet: Agreement, flexibility, and controversy
Authors: Kossoff Eric H.
Published: November 2008

Summary

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, the Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians with particular expertise in using the KD. This group was convened to create a consensus statement regarding the clinical management of the KD; the consensus statement has also been endorsed by the Child Neurology Society. Members were asked to write sections based on clinical interests and the full document was subsequently reviewed and approved by the entire group. Recommendations were made regarding evaluation of children before starting the diet, specifically in regards to ideal patient selection, pre‐KD counseling and testing, and choice of specific dietary therapy (ketogenic or less restrictive alternative diets). In addition, there was information provided regarding diet implementation (need for fasting and admission), supplementation, follow‐up management (frequency of visits as well as diet and laboratory evaluations while receiving the diet), adverse event monitoring, and timing and method of eventual KD discontinuation. This group effort highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.
KetoCalculator: A web‐based calculator for the ketogenic diet
Authors: Zupec‐Kania Beth
Published: November 2008

Summary

The classic ketogenic diet (KD) is a mathematically calculated diet with specific daily goals of fat, protein, and carbohydrate. Precise quantities of foods are then derived from these values which result in meal plans for the individual patient. The algebraic algorithm to determine a single meal requires approximately 35 calculations. This process is time consuming given that each individual requires many meals for variety and satisfaction. Computer applications can process multiple calculations in seconds. In 1997, a program was designed by this author with LifeTime Computing, a computer software company. This program was rebuilt into digital format in 2002, given the title KetoCalculator, and made available to registered dietitians on the World Wide Web (

Zupec‐Kania, 2002

).
Ketogenic ratio, calories, and fluids: Do they matter?
Authors: Wirrell Elaine C.
Published: November 2008

Summary

The ketogenic diet (KD) traditionally was initiated using specified ketogenic ratios, limited calories, and fluids. Recent work has shown that lower ketogenic ratio diets are frequently as efficacious as higher ones and result in fewer adverse effects. In animals, calorie restriction is anticonvulsant. In children, however, the need for calorie restriction is less clear, but avoidance of excessive calories may improve efficacy of the diet. There is no evidence that fluid restriction is a necessary component of the KD. Given the higher risk of nephrolithiasis, adequate fluid intake should be encouraged.
Assessing ketosis: Approaches and pitfalls
Authors: Carmant Lionel
Published: November 2008

Summary

Although the mechanism of action of the ketogenic diet (KD) remains unknown, ketones have been used as a marker of efficacy. Acetoacetate, acetone, and beta‐hydroxybutyrate can be measured in urine, blood, and breath. The value of these measures is reviewed in this paper. Future brain measures hold promise as markers of efficacy, but research focused on the mechanisms of the KD should help to develop more reliable markers of efficacy.
Long‐term health consequences of epilepsy diet treatments
Authors: Vining Eileen P. G.
Published: November 2008

Summary

The ketogenic diet (KD) typically provides a marginally healthy diet and in recent years has been used for more protracted courses of therapy. This results in concern about the impact of the diet on the general health of the child. Studies have demonstrated poor growth, dyslipidemia, kidney stones, and numerous other problems seen less frequently. Major areas of concern are reviewed as well as some emerging evidence of more beneficial long‐term health consequences beyond the expected control of seizures.
Use of the ketogenic diet in neonates and infants
Authors: Rubenstein James E.
Published: November 2008

Summary

The ketogenic diet (KD) is still viewed as virtually last‐line therapy in childhood epilepsies, and specifically as unsafe and difficult to initiate and maintain in neonates and infants. Information is presented to show that the KD is safe and efficacious in this population, and should be carefully studied to determine its real usefulness as first‐line or early therapy (one or fewer anticonvulsants) in the catastrophic epilepsies of infancy.
Medium‐chain triglyceride (MCT) ketogenic therapy
Authors: Liu Yeou‐mei Christiana
Published: November 2008

Summary

The medium‐chain triglyceride diet (MCTD) is a variant of the classic 4:1 ketogenic diet (KD) introduced in 1971 by Huttenlocher as an attempt to improve the palatability of the KD by allowing more carbohydrates yet preserving ketosis. Although initially found to be equally effective as the classic KD, use of the MCTD declined because of frequent gastrointestinal side effects such as cramps, diarrhea, and vomiting. Recently, we have used the MCTD in more than 50 patients. We have found excellent seizure control, similar to the classic KD, and with careful monitoring, we have encountered minimal side effects. The MCTD should remain a viable dietary option for children with refractory epilepsy who have large appetites, can tolerate more calories, or cannot accept the restrictions of the classic KD.
The Modified Atkins Diet
Authors: Kossoff Eric H. , Dorward Jennifer L.
Published: November 2008

Summary

In 2003, a case series was published describing the benefits of a less restrictive ketogenic diet (KD) started as an outpatient without a fast and without any restrictions on calories, fluids, or protein. This “Modified Atkins Diet” (MAD) restricts carbohydrates to 10 g/day (15 g/day in adults) while encouraging high fat foods. Now 5 years later, there have been eight prospective and retrospective studies published on this alternative dietary therapy, both in children as well as adults. In these reports, 45 (45%) have had 50–90% seizure reduction, and 28 (28%) >90% seizure reduction, which is remarkably similar to the traditional KD. This review will discuss basics and tips to best provide the MAD, evidence for its efficacy, suggestions about the role of ketosis in dietary treatment efficacy, and its side effect profile. Lastly, the possible future benefits of this treatment for new‐onset seizures, adults, neurologic conditions other than epilepsy, and developing countries of the world will be discussed.
Low glycemic index treatment: Implementation and new insights into efficacy
Authors: Pfeifer Heidi H. , Lyczkowski David A. , Thiele Elizabeth A.
Published: November 2008

Summary

Despite the substantial efficacy of the ketogenic diet (KD) in treating refractory epilepsy, use of the KD remains limited because of difficulties in implementation and tolerability. An effective alternative dietary approach is a low glycemic index treatment (LGIT), which liberalizes the extreme carbohydrate restriction of the KD but restricts the type of carbohydrate‐containing foods to those that produce relatively small changes in blood glucose. Foods with a “glycemic index” of less than 50 produce less than half the area‐under‐the‐curve elevation of blood glucose compared to a reference food. The LGIT approach produces comparable efficacy to the classic KD, but tolerability is improved and implementation is much simpler. The LGIT appears to be a viable first‐line dietary therapy for epilepsy.
Glucose transporter deficiency syndrome (GLUT1DS) and the ketogenic diet
Authors: Klepper Jörg
Published: November 2008

Summary

Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1DS, OMIM 606777) is caused by impaired glucose transport into brain mediated by GLUT1, the glucose transporter at the blood–brain barrier. The condition is diagnosed by hypoglycorrhachia, impaired glucose uptake into erythrocytes, and heterozygous mutations in the SLC2A1 gene (OMIM 138140, gene map locus 1p35‐31.3). Patients present with early‐onset epilepsy, developmental delay, and a complex movement disorder. The phenotype is highly variable and several atypical variants have been described. The ketogenic diet (KD) provides ketones as an alternative fuel to the brain. Calculation, administration, supplements, and adverse effects of the KD in GLUT1DS do not differ from patients treated for intractable childhood epilepsy. In GLUT1DS, the KD should be introduced early to meet the energy demands of the developing brain and should be maintained into puberty. Seizures are effectively controlled, but the effects on neurodevelopment and on the movement disorder are less impressive. The KD remains the treatment of choice for GLUT1DS, but recent insights into anticonvulsive diet mechanisms, animal models for GLUT1DS, and the development of alternative KDs provide new opportunities to improve the treatment of this condition.
What constitutes a relevant animal model of the ketogenic diet?
Authors: Holmes Gregory L.
Published: November 2008

Summary

Animal models of human disease have been enormously important in improving our understanding of the pathophysiological basis and the development of novel therapies. In epilepsy, modeling using both in vivo and in vitro preparations has provided insight into fundamental neuronal mechanisms. Indeed, much of our understanding of seizure mechanisms comes from animal studies. The conceptual advances in understanding basic mechanisms of epilepsies have been largely validated in humans, attesting to the validity of the rationale and providing a basis for bridging the gaps between experimental and human data. While the ketogenic diet is clearly efficacious in a wide variety of seizure types and syndromes, the mechanism of action of the diet has not been established. Animal models will continue to be enormously important in furthering our understanding of how dietary therapy can help individuals with epilepsy.
Design of dietary treatment: Humans versus rodents
Authors: Eagles Douglas A.
Published: November 2008

Summary

Ketogenic diets (KDs) are designed to create the metabolic conditions of fasting, which was among the earliest therapies discovered for epilepsy. The major measures used to evaluate dietary effectiveness have been the levels of urinary ketone bodies and the successful reduction of seizure activity. Modifications of the “classical” animal fat KD have been used in an attempt to boost ketonuria or ketonemia, increase palatability and compliance, and reduce side effects. Studies of KDs in experimental animals have been largely confined to rodents (mice and rats) for reasons of cost and convenience, and both have been found to be protected against experimentally induced seizures following consumption of KDs. Most of these studies have been designed to test hypotheses about the mechanism(s) by which reductions in carbohydrate or increases in fat result in elevated seizure threshold, decreased seizure duration, and decreased seizure severity. So far, underlying mechanisms have proven elusive. Rodent studies have led to a degree of general agreement that ketone levels per se do not correlate well with seizure protection, that reduction of glucose levels is fundamentally important, and that calorie restriction is additive to high fat diets in providing seizure protection.
Genetic influences on ketogenic diet efficacy
Authors: Dutton Stacey B. B. , Escayg Andrew
Published: November 2008

Summary

An average of 15–20% of patients on the ketogenic diet (KD) experience a >50% reduction in seizure frequency; however, 10–40% discontinue the diet due to either a lack of response or adverse side effects. This variability in patient response raises the possibility that genetic factors may influence the efficacy of the KD. As a first step towards identifying these factors, we evaluated the ability of the KD to alter seizure thresholds in four commonly used inbred mouse strains: C57BL/6J, FVB/NJ, A/J, and DBA/2J. We observed strain‐specific differences, indicating that genetic factors are likely to influence efficacy.
Ketosis and brain handling of glutamate, glutamine, and GABA
Authors: Yudkoff Marc , Daikhin Yevgeny , Horyn Oksana , Nissim Ilana , Nissim Itzhak
Published: November 2008

Summary

We hypothesize that one mechanism of the anti‐epileptic effect of the ketogenic diet is to alter brain handling of glutamate. According to this formulation, in ketotic brain astrocyte metabolism is more active, resulting in enhanced conversion of glutamate to glutamine. This allows for: (a) more efficient removal of glutamate, the most important excitatory neurotransmitter; and (b) more efficient conversion of glutamine to GABA, the major inhibitory neurotransmitter.
Ketones and brain function: Possible link to polyunsaturated fatty acids and availability of a new brain PET tracer, 11C‐acetoacetate
Authors: Pifferi Fabien , Tremblay Sébastien , Plourde Mélanie , Tremblay‐Mercier Jennifer , Bentourkia M'hamed , Cunnane Stephen C.
Published: November 2008

Summary

Changes in the metabolism of polyunsaturated fatty acids (PUFA), both in children on the high fat ketogenic diet (KD) for seizure control and in rats on a KD enriched in PUFA, raise the possibility that increased brain arachidonic acid (ARA) and/or docosahexaenoic acid (DHA) may contribute to better seizure control. Our studies with PUFA and several other reports raise the question of whether persistent ketonemia or elevated brain uptake of ketones are strictly necessary for the clinical effectiveness of the KD in intractable epilepsy. To address this question, we have developed the synthesis of carbon‐11 labeled acetoacetate (
11
C‐AcAc) for PET studies to investigate brain ketone uptake directly in humans and animals. In rats on the KD for 10 days, 11C‐AcAc uptake by the brain increased 7‐ to 8‐fold, an increase similar to that induced by 48 h fasting. In rats and humans, paired PET scans (
11
C‐AcAc followed immediately by
18
fluorodeoxyglucose) will be conducted to assess the uptake of AcAc and glucose by the brain while on the KD and in neurological disorders associated with aging.
Ketone bodies, glycolysis, and KATP channels in the mechanism of the ketogenic diet
Authors: Yellen Gary
Published: November 2008

Summary

The ketogenic diet (KD) has shown remarkable efficacy in the treatment of drug‐resistant childhood epilepsy. Our understanding of how the KD produces its anticonvulsant and antiepileptogenic effects remains incomplete, which is perhaps not surprising for a biological manipulation as sweeping as dietary change. Several hypotheses focus on ketone bodies, fuel molecules that circulate at millimolar concentrations in the blood of patients on a KD, as causative agents. Here I consider some recent evidence for one such hypothesis, involving a possible role for altered glycolysis and consequent activation of a class of potassium channels called K

ATP

channels.
Acetone as an Anticonvulsant
Authors: Likhodii Sergei , Nylen Kirk , Burnham W. McIntyre
Published: November 2008

Summary

Recent interest in the anticonvulsant effects of acetone has stemmed from studies related to the ketogenic diet (KD). The KD, a high‐fat diet used to treat drug‐resistant seizures, raises blood and brain levels of three ketones: beta‐hydroxybutyrate, acetoacetate, and acetone. An obvious question is whether these ketones have anticonvulsant properties. We found that neither beta‐hydroxybutyrate nor acetoacetate has proven to be anticonvulsant. Acetone, however, is clearly anticonvulsant at physiological, and near‐physiological, nontoxic concentrations. Despite knowledge of acetone's anticonvulsant properties since the 1930's, acetone had never been characterized using the standard animal seizure tests. In our recent experiments, acetone was found to be active in animal models of tonic–clonic seizures, typical absence seizures, complex partial seizures, and atypical absence seizures associated with Lennox–Gastaut syndrome. Therapeutic indices are either comparable or better than that of valproate, a standard broad‐spectrum anticonvulsant. A number of acetone‐like molecules have also been tested, and these also show good potency up to a “cutoff” point of nine carbons contained in the side chain. Above this number, potency disappears, suggesting the possibility of a receptor for acetone and its analogs.
Lability of GABAA receptor function in human partial epilepsy: Possible relationship to hypometabolism
Authors: Pumain René , Ahmed Mounia Sid , Kurcewicz Irène , Trottier Suzanne , Louvel Jacques , Turak Baris , Devaux Bertrand , Laschet Jacques
Published: November 2008

Summary

The function of the γ‐aminobutyric acid type A receptor (GABA

A

R) is maintained by endogenous phosphorylation. We have shown that the corresponding kinase is the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), using the locally produced glycolytic ATP. In addition, using cerebral tissue obtained during curative surgery for epilepsy, we showed that both the endogenous phosphorylation and the GABA

A

R function are significantly reduced in the “epileptogenic” cerebral cortex when compared to “control” tissue. This dysfunction likely contributes to seizure generation and/or transition from the interictal to the ictal state. Glucose utilization is decreased in the epileptogenic cortex of patients with partial epilepsy in the interictal state, but the relationship to the disorder remains unclear. We propose that this hypometabolism is related to the deficiency in the endogenous phosphorylation of GABA

A

R and the resulting greater lability of GABAergic inhibition. Several lines of evidences indeed suggest that GABAergic inhibition is costly in terms of metabolic consumption. The deficiency of this glycolysis‐dependent mechanism may thus link epileptogenicity to glucose hypometabolism. The antiepileptic effect of ketogenic diets may be mediated by the subsequent rise in the NADH/NAD+ index, which favors GABA

A

R endogenous phosphorylation and should contribute to restoration of GABAergic inhibition in the epileptogenic zone.
Calorie restriction and glucose regulation
Authors: Yamada Kelvin A.
Published: November 2008

Summary

Ketogenic diets (KDs) are effective treatments for epilepsy. The mechanisms of action are poorly understood. In some experimental seizure models, calorie restriction and hypoglycemia may augment the antiseizure effects of KDs. In addition, inhibiting glycolysis or diverting glucose from the glycolytic pathway inhibits seizures and possibly epileptogenesis, suggesting an interaction between energy regulation and the anticonvulsant actions of these interventions. Children on KDs frequently exhibit poor weight gain and have lower blood glucose levels compared to children on standard, balanced diets. Young rodents on a KD also exhibit slow weight gain, lower blood glucose and insulin levels, and elevated leptin levels. This review considers the possibility that calorie restriction, low serum glucose, and KDs share common cell signaling pathways to alter brain excitability. AMP‐activated protein kinase (AMPK) is an attractive candidate signaling protein that could link energy balance to gene expression in such a way so as to reduce brain excitability.
Possible mechanisms for the anticonvulsant activity of fructose‐1,6‐diphosphate
Authors: Stringer Janet L. , Xu Kaiping
Published: November 2008

Summary

Fructose‐1,6‐diphosphate (FDP), an intracellular metabolite of glucose, has anticonvulsant activity in several models of acute seizures in laboratory animals. The anticonvulsant effect of FDP is most likely due to a direct effect since intraperitoneal and oral administration results in significant increases in brain levels. A number of mechanisms have been proposed for this action of FDP. One possibility is that peripheral administration of FDP results in changes in brain metabolism that are anticonvulsant. Glucose can be metabolized through the glycolytic or pentose phosphate pathway. There is evidence that the pentose phosphate pathway is more active in the brain than in other tissues, and that, in the presence of elevated levels of FDP, the majority of glucose is metabolized by the pentose phosphate pathway. The pentose phosphate pathway generates NADPH, which is used to reduce glutathione. The reduced form of endogenous glutathione has been shown to have anticonvulsant activity. Taken together, the data suggest a hypothesis that exogenously administered FDP gets into the brain and astrocytes where it increases the flux of glucose through the pentose phosphate pathway, generating additional NADPH for the reduction of glutathione.
The contribution of norepinephrine and orexigenic neuropeptides to the anticonvulsant effect of the ketogenic diet
Authors: Weinshenker David
Published: November 2008

Summary

The ketogenic diet (KD) is a high‐fat, low‐carbohydrate, low‐protein diet used to treat refractory epilepsy. Despite its efficacy and many years of investigation, the mechanism by which the KD exerts its anticonvulsant effect remains controversial and poorly understood. The purpose of this article is to review the available data considering two classes of molecules that may contribute to the anticonvulsant effect of the KD:  norepinephrine and the orexigenic neuropeptides galanin and neuropeptide Y.