551 results on '"Freeman, JL"'
Search Results
2. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination
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Ramanathan, Sudarshini, Mohammad, Shekeeb, Tantsis, Esther, Nguyen, Tina Kim, Merheb, Vera, Fung, Victor S C, White, Owen Bruce, Broadley, Simon, Lechner-Scott, Jeannette, Vucic, Steve, Henderson, Andrew P D, Barnett, Michael Harry, Reddel, Stephen W, Brilot, Fabienne, Dale, Russell C, Andrews, Pi, Barton, Jl, Burrow, Jnc, Butzkueven, H, Cairns, Ag, Calvert, S, Caruana, P, Chelakkadan, S, Clark, D, Fraser, Cl, Freeman, Jl, Gill, D, Grattan-smith, Pj, Gupta, S, Hardy, Ta, Kothur, K, Ling, Sr, Lopez, Ja, Malone, S, Marriott, Mp, Nosadini, M, O’grady, Gl, Orr, Cf, Ouvrier, R, Parratt, J, Patrick, E, Pilli, D, Riminton, Ds, Riney, K, Rodriguez-casero, V, Ryan, Mm, Scheffer, Ie, Shah, Uh, Shuey, N, Spooner, Cg, Subramanian, Gm, Tea, F, Thomas, T, Thompson, J, Troedson, C, Ware, Tl, Webster, Ri, Yiannikas, C, Yiu, Em, and Zou, A
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- 2018
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3. 'Ask yourself WHY you want to track yourself': Co-Designing a Self-Tracking Guide with Teenagers
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Freeman, JL and Curtis, AN
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Teenagers often engage with Personal Informatics tools for health and fitness without support or guidance specific to their individual experiences. There is a lack of research on how putting teens at the center of designing educational resources might empower young users to harness the affordances of self-tracking tools that are of most value to them. To address this gap, we ran five online co-design workshops with 44 teenagers (aged 13-18 years) in the United Kingdom to design a self-tracking guide for teens. We focused on content, presentation of information, and distribution strategy. Our findings highlight the complexity of creating resources which adeptly capture the needs of this diverse user group. To successfully build interactive educational resources appropriate for teens’ positive engagement with health-related self-tracking tools, designers and researchers must prioritize teen-centered design with a focus on: (1) teens’ core reasons for self-tracking and (2) opportunities for social support and community-building.
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- 2022
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4. Unclassified white matter disorders: A diagnostic journey requiring close collaboration between clinical and laboratory services
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Stutterd, CA, Vanderver, A, Lockhart, PJ, Helman, G, Pope, K, Uebergang, E, Love, C, Delatycki, MB, Thorburn, D, Mackay, MT, Peters, H, Kornberg, AJ, Patel, C, Rodriguez-Casero, V, Waak, M, Silberstein, J, Sinclair, A, Nolan, M, Field, M, Davis, MR, Fahey, M, Scheffer, IE, Freeman, JL, Wolf, N, Taft, RJ, van der Knaap, MS, Simons, C, Leventer, RJ, Stutterd, CA, Vanderver, A, Lockhart, PJ, Helman, G, Pope, K, Uebergang, E, Love, C, Delatycki, MB, Thorburn, D, Mackay, MT, Peters, H, Kornberg, AJ, Patel, C, Rodriguez-Casero, V, Waak, M, Silberstein, J, Sinclair, A, Nolan, M, Field, M, Davis, MR, Fahey, M, Scheffer, IE, Freeman, JL, Wolf, N, Taft, RJ, van der Knaap, MS, Simons, C, and Leventer, RJ
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BACKGROUND: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended. AIM: This study aimed to identify the genetic causes for a group of individuals with unclassified white matter disorders with suspected genetic aetiology and highlight the investigations required when the initial testing is non-diagnostic. METHODS: Twenty-six individuals from 22 families with unclassified white matter disorders underwent deep phenotyping and genome sequencing performed on trio, or larger, family groups. Functional studies and transcriptomics were used to resolve variants of uncertain significance with potential clinical relevance. RESULTS: Causative or candidate variants were identified in 15/22 (68.2%) families. Six of the 15 implicated genes had been previously associated with white matter disease (COL4A1, NDUFV1, SLC17A5, TUBB4A, BOLA3, DARS2). Patients with variants in the latter two presented with an atypical phenotype. The other nine genes had not been specifically associated with white matter disease at the time of diagnosis and included genes associated with monogenic syndromes, developmental disorders, and developmental and epileptic encephalopathies (STAG2, LSS, FIG4, GLS, PMPCA, SPTBN1, AGO2, SCN2A, SCN8A). Consequently, only 46% of the diagnoses would have been made via a current leukodystrophy gene panel test. DISCUSSION: These results confirm the importance of broad genomic testing for patients with white matter disorders. The high diagnostic yield reflects the integration of deep phenotyping, whole genome sequencing, trio analysis, functional studies, and transcriptomic analyses. CONC
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- 2022
5. Sporadic hypothalamic hamartoma is a ciliopathy with somatic and bi-allelic contributions
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Green, TE, Motelow, JE, Bennett, MF, Ye, Z, Bennett, CA, Griffin, NG, Damiano, JA, Leventer, RJ, Freeman, JL, Harvey, AS, Lockhart, PJ, Sadleir, LG, Boys, A, Scheffer, IE, Major, H, Darbro, BW, Bahlo, M, Goldstein, DB, Kerrigan, JF, Heinzen, EL, Berkovic, SF, Hildebrand, MS, Green, TE, Motelow, JE, Bennett, MF, Ye, Z, Bennett, CA, Griffin, NG, Damiano, JA, Leventer, RJ, Freeman, JL, Harvey, AS, Lockhart, PJ, Sadleir, LG, Boys, A, Scheffer, IE, Major, H, Darbro, BW, Bahlo, M, Goldstein, DB, Kerrigan, JF, Heinzen, EL, Berkovic, SF, and Hildebrand, MS
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Hypothalamic hamartoma with gelastic seizures is a well-established cause of drug-resistant epilepsy in early life. The development of novel surgical techniques has permitted the genomic interrogation of hypothalamic hamartoma tissue. This has revealed causative mosaic variants within GLI3, OFD1 and other key regulators of the sonic-hedgehog pathway in a minority of cases. Sonic-hedgehog signalling proteins localize to the cellular organelle primary cilia. We therefore explored the hypothesis that cilia gene variants may underlie hitherto unsolved cases of sporadic hypothalamic hamartoma. We performed high-depth exome sequencing and chromosomal microarray on surgically resected hypothalamic hamartoma tissue and paired leukocyte-derived DNA from 27 patients. We searched for both germline and somatic variants under both dominant and bi-allelic genetic models. In hamartoma-derived DNA of seven patients we identified bi-allelic (one germline, one somatic) variants within one of four cilia genes-DYNC2I1, DYNC2H1, IFT140 or SMO. In eight patients, we identified single somatic variants in the previously established hypothalamic hamartoma disease genes GLI3 or OFD1. Overall, we established a plausible molecular cause for 15/27 (56%) patients. Here, we expand the genetic architecture beyond single variants within dominant disease genes that cause sporadic hypothalamic hamartoma to bi-allelic (one germline/one somatic) variants, implicate three novel cilia genes and reconceptualize the disorder as a ciliopathy.
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- 2022
6. A pilot randomised placebo-controlled trial of cannabidiol to reduce severe behavioural problems in children and adolescents with intellectual disability
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Efron, D, Freeman, JL, Cranswick, N, Payne, JM, Mulraney, M, Prakash, C, Lee, KJ, Taylor, K, Williams, K, Efron, D, Freeman, JL, Cranswick, N, Payne, JM, Mulraney, M, Prakash, C, Lee, KJ, Taylor, K, and Williams, K
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AIMS: Severe behavioural problems (SBP) are a major contributor to morbidity in children with intellectual disability (ID). Medications used to treat SBP in ID are associated with a high risk of side effects. Cannabidiol has potential therapeutic effects in SBP. This pilot study aimed to investigate the feasibility of conducting a randomised placebo-controlled trial of cannabidiol to reduce SBP in children with ID. METHODS: This is a double-blind, placebo-controlled, two-armed, parallel-design, randomised controlled trial of cannabidiol in children aged 8-16 years with ID and SBP. Participants were randomised 1:1 to receive either 98% cannabidiol in oil (Tilray, Canada) or placebo orally for 8 weeks. The dose was up-titrated over 9 days to 20 mg/kg/day in two divided doses, with a maximum dose of 500 mg twice/day. The feasibility and acceptability of all study components were assessed. RESULTS: Eight children were randomised, and all completed the full study protocol. There were no serious adverse events or drop-outs. Protocol adherence for key study components was excellent: study visits 100%, medication adherence 100%, blood tests 92% and questionnaire completion 88%. Parents reported a high degree of acceptability with the study design. All parents reported they would recommend the study to other families with children with similar problems. There was an efficacy signal in favour of active drug. CONCLUSIONS: The findings suggest that the study protocol is feasible and acceptable to patients with ID and SBP and their families.
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- 2021
7. Mental healthcare for children with chronic conditions: A qualitative study
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Jones, R, Hiscock, H, Wurzel, D, Kao, KT, Freeman, JL, Ride, J, Jones, R, Hiscock, H, Wurzel, D, Kao, KT, Freeman, JL, and Ride, J
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Objective To explore parent perspectives on accessing mental healthcare for children with a chronic physical health condition. Design Qualitative research using semistructured interviews and Framework Analysis. Rankings were used to select attributes for a Discrete Choice Experiment (DCE). Setting Four specialty outpatient clinics (diabetes, epilepsy, bronchiectasis unrelated to cystic fibrosis and epidermolysis bullosa) at an Australian tertiary paediatric hospital. Participants Eighteen parents of children with a chronical physical health condition. Results Most parents identified the child’s general practitioner and/or hospital team as an initial pathway to seek help if they were worried about their child’s mental health. Parents see mental healthcare as part of care for the whole child and want the outpatient clinics to proactively discuss child and family mental health, as well as refer to appropriate services as needed. The hospital being a familiar, child-friendly environment was identified as a key reason the hospital might be a desired place to access mental healthcare, as previous research has found. Six attributes of mental health services were identified as important and will be included in an upcoming DCE: travel time, cost, wait time, available hours, knowledge of physical health condition, and recommendation. Conclusions This study highlights the opportunity presented in specialist outpatient clinics to address the often unmet mental healthcare needs of children with chronic physical health conditions. Parents identified practical ways for outpatient clinics to better facilitate access to mental healthcare. These will be further explored through a quantitative study of parent preferences.
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- 2021
8. An unexpected disease course for a patient with diffuse midline glioma
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Malalasekera, VS, D'Arcy, CE, Mignone, C, Wray, AC, Nazarian, J, Freeman, JL, Hansford, JR, Malalasekera, VS, D'Arcy, CE, Mignone, C, Wray, AC, Nazarian, J, Freeman, JL, and Hansford, JR
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- 2021
9. The severe epilepsy syndromes of infancy: A population-based study
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Howell, KB, Freeman, JL, Mackay, MT, Fahey, MC, Archer, J, Berkovic, SF, Chan, E, Dabscheck, G, Eggers, S, Hayman, M, Holberton, J, Hunt, RW, Jacobs, SE, Kornberg, AJ, Leventer, RJ, Mandelstam, S, McMahon, JM, Mefford, HC, Panetta, J, Riseley, J, Rodriguez-Casero, V, Ryan, MM, Schneider, AL, Smith, LJ, Stark, Z, Wong, F, Yiu, EM, Scheffer, IE, Harvey, AS, Howell, KB, Freeman, JL, Mackay, MT, Fahey, MC, Archer, J, Berkovic, SF, Chan, E, Dabscheck, G, Eggers, S, Hayman, M, Holberton, J, Hunt, RW, Jacobs, SE, Kornberg, AJ, Leventer, RJ, Mandelstam, S, McMahon, JM, Mefford, HC, Panetta, J, Riseley, J, Rodriguez-Casero, V, Ryan, MM, Schneider, AL, Smith, LJ, Stark, Z, Wong, F, Yiu, EM, Scheffer, IE, and Harvey, AS
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OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initi
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- 2021
10. Developmental and epilepsy spectrum ofKCNB1encephalopathy with long-term outcome
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Bar, C, Kuchenbuch, M, Barcia, G, Schneider, A, Jennesson, M, Le Guyader, G, Lesca, G, Mignot, C, Montomoli, M, Parrini, E, Isnard, H, Rolland, A, Keren, B, Afenjar, A, Dorison, N, Sadleir, LG, Breuillard, D, Levy, R, Rio, M, Dupont, S, Negrin, S, Danieli, A, Scalais, E, De Saint Martin, A, El Chehadeh, S, Chelly, J, Poisson, A, Lebre, A-S, Nica, A, Odent, S, Sekhara, T, Brankovic, V, Goldenberg, A, Vrielynck, P, Lederer, D, Maurey, H, Terrone, G, Besmond, C, Hubert, L, Berquin, P, Billette de Villemeur, T, Isidor, B, Freeman, JL, Mefford, HC, Myers, CT, Howell, KB, Rodriguez-Sacristan Cascajo, A, Meyer, P, Genevieve, D, Guet, A, Doummar, D, Durigneux, J, van Dooren, MF, de Wit, MCY, Gerard, M, Marey, I, Munnich, A, Guerrini, R, Scheffer, IE, Kabashi, E, Nabbout, R, Bar, C, Kuchenbuch, M, Barcia, G, Schneider, A, Jennesson, M, Le Guyader, G, Lesca, G, Mignot, C, Montomoli, M, Parrini, E, Isnard, H, Rolland, A, Keren, B, Afenjar, A, Dorison, N, Sadleir, LG, Breuillard, D, Levy, R, Rio, M, Dupont, S, Negrin, S, Danieli, A, Scalais, E, De Saint Martin, A, El Chehadeh, S, Chelly, J, Poisson, A, Lebre, A-S, Nica, A, Odent, S, Sekhara, T, Brankovic, V, Goldenberg, A, Vrielynck, P, Lederer, D, Maurey, H, Terrone, G, Besmond, C, Hubert, L, Berquin, P, Billette de Villemeur, T, Isidor, B, Freeman, JL, Mefford, HC, Myers, CT, Howell, KB, Rodriguez-Sacristan Cascajo, A, Meyer, P, Genevieve, D, Guet, A, Doummar, D, Durigneux, J, van Dooren, MF, de Wit, MCY, Gerard, M, Marey, I, Munnich, A, Guerrini, R, Scheffer, IE, Kabashi, E, and Nabbout, R
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OBJECTIVE: We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy. METHODS: We collected genetic, clinical, electroencephalographic, and imaging data of individuals with KCNB1 pathogenic variants recruited through an international collaboration, with the support of the family association "KCNB1 France." Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the long-term outcome in patients older than 12 years from our series and from literature. RESULTS: Our series included 36 patients (21 males, median age = 10 years, range = 1.6 months-34 years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10 months, range = 10 days-3.5 years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5 years, range = 18 months-25 years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals with KCNB1 pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n = 41/61) and autistic features in 56% (n = 32/57). Long-term outcome in 22 individuals older than 12 years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. SIGNIFICANCE: Our study describes the phenotypic spectrum of KCNB1 encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechani
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- 2020
11. Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease.
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Bursle, C, Yiu, EM, Yeung, A, Freeman, JL, Stutterd, C, Leventer, RJ, Vanderver, A, Yaplito-Lee, J, Bursle, C, Yiu, EM, Yeung, A, Freeman, JL, Stutterd, C, Leventer, RJ, Vanderver, A, and Yaplito-Lee, J
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We report two unrelated patients with infantile onset leukoencephalopathy with vanishing white matter (VWM) and hyperinsulinaemic hypoglycaemia. To our knowledge, this association has not been described previously. Both patients had compound heterozygous pathogenic variants in EIF2B4 detected on exome sequencing and absence of other variants which might explain the hyperinsulinism. Hypoglycaemia became apparent at 6 and 8 months, respectively, although in one patient, transient neonatal hypoglycaemia was also documented. One patient responded to diazoxide and the other was managed with continuous nasogastric feeding. We hypothesise that the pathophysiology of hyperinsulinism in VWM may involve dysregulation of transcription of genes related to insulin secretion.
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- 2020
12. Protocol for a single patient therapy plan: A randomised, double-blind, placebo-controlled N-of-1 trial to assess the efficacy of cannabidiol in patients with intractable epilepsy
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Ong, KS, Carlin, JB, Fahey, M, Freeman, JL, Scheffer, IE, Gillam, L, Anderson, M, Huque, MH, Legge, D, Dirnbauer, N, Lilley, B, Slota-Kan, S, Cranswick, N, Ong, KS, Carlin, JB, Fahey, M, Freeman, JL, Scheffer, IE, Gillam, L, Anderson, M, Huque, MH, Legge, D, Dirnbauer, N, Lilley, B, Slota-Kan, S, and Cranswick, N
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Aim This paper describes the use of the single patient therapy plan (SPTP). The SPTP has been designed to assess the efficacy at an individual level of a commercially available cannabinoid product, cannabidiol, in reducing seizure frequency in paediatric patients with intractable epilepsy. Methods The SPTP is a randomised, double‐blind, placebo‐controlled N‐of‐1 trial designed to assess the efficacy of treatment in a neurology outpatient setting. The primary objective of the SPTP is to assess the efficacy of cannabidiol in reducing seizure frequency in each patient with intractable epilepsy, with change in seizure frequency being the primary outcome of interest. The analysis adopts a Bayesian approach, which provides results in the form of posterior probabilities that various levels of benefit (based on the primary outcome measure, seizure frequency) have been achieved under active treatment compared to placebo, accompanied by decision rules that provide thresholds for deciding whether treatment has been successful in the individual patient. The SPTP arrangement is most accurately considered part of clinical practice rather than research, since it is aimed at making clinical treatment decisions for individual patients and is not testing a hypothesis or collecting aggregate data. Therefore, Human Research Ethics Committee approval was considered not to be required, although it is recommended that hospital Clinical Ethics Committees provide ethical oversight. Conclusion: These SPTP resources are made available so that they may inform clinical practice in the treatment of severe epilepsy or adapted for use in other conditions.
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- 2020
13. Does cannabidiol reduce severe behavioural problems in children with intellectual disability? Study protocol for a pilot single-site phase I/II randomised placebo controlled trial
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Efron, D, Taylor, K, Payne, JM, Freeman, JL, Cranswick, N, Mulraney, M, Prakash, C, Lee, KJ, Williams, K, Efron, D, Taylor, K, Payne, JM, Freeman, JL, Cranswick, N, Mulraney, M, Prakash, C, Lee, KJ, and Williams, K
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INTRODUCTION: Severe behavioural problems (SBPs) are a common contributor to morbidity and reduced quality of life in children with intellectual disability (ID). Current medication treatment for SBP is associated with a high risk of side effects. Innovative and safe interventions are urgently needed. Anecdotal reports and preliminary research suggest that medicinal cannabis may be effective in managing SBP in children with developmental disabilities. In particular, cannabidiol (CBD) may be a plausible and safe alternative to current medications. Families who are in urgent need of solutions are seeking cannabis for their ID children with SBP. However there is no evidence from randomised controlled trials to support the use of CBD for SBP. This pilot study aims to investigate the feasibility of conducting a randomised placebo-controlled trial of CBD to improve SBP in children with ID. METHODS AND ANALYSIS: This is a single-site, double-blind, parallel-group, randomised, placebo-controlled pilot study of 10 participants comparing 98% CBD oil with placebo in reducing SBP in children aged 8-16 years with ID. Eligible participants will be randomised 1:1 to receive either CBD 20 mg/kg/day or placebo for 8 weeks. Data will be collected regarding the feasibility and acceptability of all study components, including recruitment, drop-out rate, study visit attendance, protocol adherence and the time burden of parent questionnaires. Safety outcomes and adverse events will be recorded. All data will be reported using descriptive statistics. These data will inform the design of a full scale randomised controlled trial to evaluate the efficacy of CBD in this patient group. ETHICS AND DISSEMINATION: This protocol has received ethics approval from the Royal Children's Hospital ethics committee (Human Research Ethics Committee no. 38236). Results will be disseminated through peer-reviewed journals, professional networks, conferences and social media. TRIAL REGISTRATION NUMBER: ACTRN12
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- 2020
14. Epidemiology and etiology of infantile developmental and epileptic encephalopathies in Tasmania
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Ware, TL, Huskins, SR, Grinton, BE, Liu, Y-C, Bennett, MF, Harvey, M, McMahon, J, Andreopoulos-Malikotsinas, D, Bahlo, M, Howell, KB, Hildebrand, MS, Damiano, JA, Rosenfeld, A, Mackay, MT, Mandelstam, S, Leventer, RJ, Harvey, AS, Freeman, JL, Scheffer, IE, Jones, DL, Berkovic, SF, Ware, TL, Huskins, SR, Grinton, BE, Liu, Y-C, Bennett, MF, Harvey, M, McMahon, J, Andreopoulos-Malikotsinas, D, Bahlo, M, Howell, KB, Hildebrand, MS, Damiano, JA, Rosenfeld, A, Mackay, MT, Mandelstam, S, Leventer, RJ, Harvey, AS, Freeman, JL, Scheffer, IE, Jones, DL, and Berkovic, SF
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We sought to determine incidence, etiologies, and yield of genetic testing in infantile onset developmental and epileptic encephalopathies (DEEs) in a population isolate, with an intensive multistage approach. Infants born in Tasmania between 2011 and 2016, with seizure onset <2 years of age, epileptiform EEG, frequent seizures, and developmental impairment, were included. Following review of EEG databases, medical records, brain MRIs, and other investigations, clinical genetic testing was undertaken with subsequent research interrogation of whole exome sequencing (WES) in unsolved cases. The incidence of infantile DEEs was 0.44/1000 per year (95% confidence interval 0.25 to 0.71), with 16 cases ascertained. The etiology was structural in 5/16 cases. A genetic basis was identified in 6 of the remaining 11 cases (3 gene panel, 3 WES). In two further cases, WES identified novel variants with strong in silico data; however, paternal DNA was not available to support pathogenicity. The etiology was not determined in 3/16 (19%) cases, with a candidate gene identified in one of these. Pursuing clinical imaging and genetic testing followed by WES at an intensive research level can give a high diagnostic yield in the infantile DEEs, providing a solid base for prognostic and genetic counseling.
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- 2019
15. Lacosamide in children with drug-resistant epilepsy
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Ruegger, AD, Freeman, JL, Harvey, AS, Ruegger, AD, Freeman, JL, and Harvey, AS
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AIM: To assess the effectiveness and tolerability of lacosamide in paediatric clinical practice. METHODS: A search of our hospital's pharmacy database yielded all children <16 years old dispensed lacosamide for drug-resistant epilepsy between January 2011 and June 2016. Medical records were reviewed for clinical and drug details. Continued treatment for ≥12 months was considered an indicator of effectiveness and tolerability. RESULTS: A total of 107 children (61 boys) satisfied inclusion criteria. Median age at lacosamide commencement was 9.9 years (interquartile range 6.7-13.7). Of those children, 57 (53%) children had focal epilepsy, with focal motor or impaired awareness seizures most commonly reported; 50 (47%) children had generalised epilepsy, most with tonic-clonic seizures, tonic seizures or epileptic spasms; 83 (78%) children had an intellectual disability, 24 (22%) had a physical disability and 22 (21%) had an autism spectrum disorder; 69 (65%) children continued lacosamide for ≥12 months. Reasons for discontinuation before 12 months in 38 (35%) children included ineffectiveness in 25 (66%), adverse events in 7 (18%) and worsening of seizures in 2 (5%). The most common adverse events were drowsiness, behavioural changes, unsteadiness, nausea and vomiting. Epilepsy type and comorbidities were not associated with continuation or reasons for discontinuation. CONCLUSIONS: Most children continued treatment with lacosamide, suggesting effectiveness and tolerability. Lacosamide may prove to be a useful, 'broad-spectrum' antiepileptic medication in children for focal and generalised epilepsies and in association with comorbidities.
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- 2019
16. Acute flaccid myelitis in childhood: a retrospective cohort study
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Andersen, EW, Kornberg, AJ, Freeman, JL, Leventer, RJ, Ryan, MM, Andersen, EW, Kornberg, AJ, Freeman, JL, Leventer, RJ, and Ryan, MM
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BACKGROUND AND PURPOSE: Clusters of acute limb weakness in paediatric patients have been linked to outbreaks of non-polio enteroviruses, termed acute flaccid myelitis (AFM). Outside these clusters, in countries where polio is not endemic, this poliomyelitic-like illness is rare in childhood and its natural history is not well defined. We describe presenting features, investigation findings and long-term outcome of a series of children with AFM. METHODS: This was a retrospective cohort study. RESULTS: Eight children (six females) aged 3 months to 8 years (median age 5 years) met case criteria. Initial symptoms were pain (n = 7) followed by limb weakness with hypotonia (n = 8). Flaccid paralysis occurred in only three patients. Two had cranial nerve dysfunction. Magnetic resonance imaging of the spinal cord demonstrated grey matter involvement particularly affecting the anterior cord, with longitudinally extensive changes in three children. Cerebrospinal fluid examination showed pleocytosis in six children with raised cerebrospinal fluid protein in five. Nerve conduction and electromyography findings were consistent with a motor neuronopathy. Residual deficits were common, with moderate to severe weakness seen in five patients. Median follow-up was 28 months (range 17-108 months, 30.4 patient years in total). CONCLUSIONS: Acute flaccid myelitis is an uncommon condition in childhood with a high rate of significant long-term morbidity. AFM should be considered in children presenting with acute limb pain and weakness.
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- 2017
17. Impaired bone and muscle development in young people treated with antiepileptic drugs
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Simm, PJ, Seah, S, Gorelik, A, Gilbert, L, Nuguid, J, Werther, GA, Mackay, MT, Freeman, JL, Petty, SJ, Wark, JD, Simm, PJ, Seah, S, Gorelik, A, Gilbert, L, Nuguid, J, Werther, GA, Mackay, MT, Freeman, JL, Petty, SJ, and Wark, JD
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OBJECTIVE: Antiepileptic drugs (AEDs) are associated with reduced bone density, balance impairment, and increased fracture risk in adults. However, pediatric data are limited. Therefore, we aimed to examine bone, muscle, and balance outcomes in young patients taking AEDs. METHODS: We undertook a case-control study utilizing an AED exposure-discordant matched-pair approach. Subjects were aged 5-18 years with at least 12 months of AED exposure. Pairs were twins, nontwin siblings and first cousins, sex- and age-matched (to within 2 years), allowing for greater power than with unrelated control subjects. Dual energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and muscle force/balance were tested, with questionnaires were administered for bone health and epilepsy details. RESULTS: Twenty-three pairs were recruited, (median age 12.9 years [subjects] and 13.5 years [controls])-7 twin, 14 sibling, and 2 cousin pairs. Those taking AEDs had an increased prevalence of fractures (15 fractures in 8 subjects, compared with 4 fractures in 3 controls, p < 0.01). Trabecular volumetric bone mineral density (vBMD) measured by pQCT at the 4% site (tibia) was reduced by 14% (p = 0.03) in subjects. Subjects exerted a decreased maximum force compared to body weight (Fmax total/g) at the tibia. There were no differences seen in either bone mineral parameters measured by DXA or balance measures. SIGNIFICANCE: Young people taking AEDs reported more fractures and had reductions in tibial vBMD and lower limb muscle force compared to their matched controls. These findings suggest that further exploration of bone health issues of young patients on AED therapy is required. Longitudinal studies are required to confirm these changes in the muscle-bone unit and to further explore the clinical outcomes.
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- 2017
18. Acute bilateral myopia caused by lamotrigine-induced uveal effusions
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Woodcock, IR, Taylor, LE, Ruddle, JB, Freeman, JL, Dabscheck, G, Woodcock, IR, Taylor, LE, Ruddle, JB, Freeman, JL, and Dabscheck, G
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- 2017
19. Benefits of screening mammography extend to women age 75 and older. (Abstracts: a digest of recent research in geriatric care)
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Randolph, WM, Goodwin, JS, Mahnken, JD, and Freeman, JL
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Mammography -- Usage ,Breast cancer -- Diagnosis ,Health ,Seniors - Abstract
Offering regular screening mammograms to women age 75 and older may provide the same benefits afforded to younger women in terms of size and stage of tumor at diagnosis, according [...]
- Published
- 2003
20. Tonic seizures of Lennox-Gastaut syndrome: Periictal single-photon emission computed tomography suggests a corticopontine network
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Intusoma, U, Abbott, DF, Masterton, RAJ, Stagnitti, MR, Newton, MR, Jackson, GD, Freeman, JL, Harvey, AS, Archer, JS, Intusoma, U, Abbott, DF, Masterton, RAJ, Stagnitti, MR, Newton, MR, Jackson, GD, Freeman, JL, Harvey, AS, and Archer, JS
- Abstract
PURPOSE: Lennox-Gastaut syndrome (LGS) is a severe epileptic disorder with characteristic electroclinical features but diverse etiologies. The shared electroclinical characteristics suggest that common cerebral networks are involved in generating seizures. We sought to reveal these networks by comparing ictal and interictal single-photon emission computed tomography (SPECT). METHODS: We identified 10 ictal-interictal SPECT pairs from seven patients with LGS (median age 11 years; range 1-38) who were studied during video electroencephalography (EEG)-confirmed tonic seizures. We performed a voxel-wise comparison of ictal and interictal SPECT studies across the group. The evolution of blood flow changes was explored by examining early and late injection groups. KEY FINDINGS: Median duration of tonic seizures was 10 s (range 6-29 s), and injection latency from seizure offset was -8 to 48 s. In the early injection group (<10 s; three studies), there was hyperperfusion over pons and cerebellar hemispheres (p < 0.05 cluster corrected family wise error), and hypoperfusion bilaterally over the pericentral region, with a trend toward hyperperfusion over bilateral superior and middle frontal gyri, and lateral parietal cortex. In the late injection group, there was hyperperfusion over midline and lateral cerebellar regions, with hypoperfusion widely over bilateral frontal regions. SIGNIFICANCE: This study suggests that the tonic seizures of LGS result from activity in a network, containing bilateral frontal and parietal association areas and the pons. We postulate that tonic seizures recruit the corticoreticular system, which connects frontal attentional areas to the pontine reticular formation, and is normally responsible for postural tone and orienting behavior.
- Published
- 2013
21. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
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Carvill, GL, Heavin, SB, Yendle, SC, McMahon, JM, O'Roak, BJ, Cook, J, Khan, A, Dorschner, MO, Weaver, M, Calvert, S, Malone, S, Wallace, G, Stanley, T, Bye, AME, Bleasel, A, Howell, KB, Kivity, S, Mackay, MT, Rodriguez-Casero, V, Webster, R, Korczyn, A, Afawi, Z, Zelnick, N, Lerman-Sagie, T, Lev, D, Moller, RS, Gill, D, Andrade, DM, Freeman, JL, Sadleir, LG, Shendure, J, Berkovic, SF, Scheffer, IE, Mefford, HC, Carvill, GL, Heavin, SB, Yendle, SC, McMahon, JM, O'Roak, BJ, Cook, J, Khan, A, Dorschner, MO, Weaver, M, Calvert, S, Malone, S, Wallace, G, Stanley, T, Bye, AME, Bleasel, A, Howell, KB, Kivity, S, Mackay, MT, Rodriguez-Casero, V, Webster, R, Korczyn, A, Afawi, Z, Zelnick, N, Lerman-Sagie, T, Lev, D, Moller, RS, Gill, D, Andrade, DM, Freeman, JL, Sadleir, LG, Shendure, J, Berkovic, SF, Scheffer, IE, and Mefford, HC
- Abstract
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.
- Published
- 2013
22. Beta 2-adrenergic receptor stimulated, G protein-coupled receptor kinase 2 mediated, phosphorylation of ribosomal protein P2
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Freeman, Jl, Gonzalo, P., Pitcher, Ja, Claing, A., Lavergne, Jp, Reboud, Jp, Lefkowitz, Rj, and Deleage, Gilbert
- Subjects
enzymes and coenzymes (carbohydrates) ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology - Abstract
G protein-coupled receptor kinases are well characterized for their ability to phosphorylate and desensitize G protein-coupled receptors (GPCRs). In addition to phosphorylating the beta2-adrenergic receptor (beta2AR) and other receptors, G protein-coupled receptor kinase 2 (GRK2) can also phosphorylate tubulin, a nonreceptor substrate. To identify novel nonreceptor substrates of GRK2, we used two-dimensional gel electrophoresis to find cellular proteins that were phosphorylated upon agonist-stimulation of the beta2AR in a GRK2-dependent manner. The ribosomal protein P2 was identified as an endogenous HEK-293 cell protein whose phosphorylation was increased following agonist stimulation of the beta2AR under conditions where tyrosine kinases, PKC and PKA, were inhibited. P2 along with its other family members, P0 and P1, constitutes a part of the elongation factor-binding site connected to the GTPase center in the 60S ribosomal subunit. Phosphorylation of P2 is known to regulate protein synthesis in vitro. Further, P2 and P1 are shown to be good in vitro substrates for GRK2 with K(M) values approximating 1 microM. The phosphorylation sites in GRK2-phosphorylated P2 are identified (S102 and S105) and are identical to the sites known to regulate P2 activity. When the 60S subunit deprived of endogenous P1 and P2 is reconstituted with GRK2-phosphorylated P2 and unphosphorylated P1, translational activity is greatly enhanced. These findings suggest a previously unrecognized relationship between GPCR activation and the translational control of gene expression mediated by GRK2 activation and P2 phosphorylation and represent a potential novel signaling pathway responsible for P2 phosphorylation in mammals.G protein-coupled receptor kinases are well characterized for their ability to phosphorylate and desensitize G protein-coupled receptors (GPCRs). In addition to phosphorylating the beta2-adrenergic receptor (beta2AR) and other receptors, G protein-coupled receptor kinase 2 (GRK2) can also phosphorylate tubulin, a nonreceptor substrate. To identify novel nonreceptor substrates of GRK2, we used two-dimensional gel electrophoresis to find cellular proteins that were phosphorylated upon agonist-stimulation of the beta2AR in a GRK2-dependent manner. The ribosomal protein P2 was identified as an endogenous HEK-293 cell protein whose phosphorylation was increased following agonist stimulation of the beta2AR under conditions where tyrosine kinases, PKC and PKA, were inhibited. P2 along with its other family members, P0 and P1, constitutes a part of the elongation factor-binding site connected to the GTPase center in the 60S ribosomal subunit. Phosphorylation of P2 is known to regulate protein synthesis in vitro. Further, P2 and P1 are shown to be good in vitro substrates for GRK2 with K(M) values approximating 1 microM. The phosphorylation sites in GRK2-phosphorylated P2 are identified (S102 and S105) and are identical to the sites known to regulate P2 activity. When the 60S subunit deprived of endogenous P1 and P2 is reconstituted with GRK2-phosphorylated P2 and unphosphorylated P1, translational activity is greatly enhanced. These findings suggest a previously unrecognized relationship between GPCR activation and the translational control of gene expression mediated by GRK2 activation and P2 phosphorylation and represent a potential novel signaling pathway responsible for P2 phosphorylation in mammals.
- Published
- 2002
23. Prognostic factors in patients with multiple recurrences of well-differentiated thyroid carcinoma
- Author
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Freeman, JL, Holler, T, Theriault, J, Payne, RJ, Clark, J, Eski, S, Freeman, JL, Holler, T, Theriault, J, Payne, RJ, Clark, J, and Eski, S
- Abstract
Introduction. Patients with multiple recurrences of well-differentiated thyroid carcinoma (WDTC) have markedly reduced overall survival when compared with those who have ≤ 1 recurrence of their disease. The purpose of this investigation is to identify prognostic factors for mortality in this subgroup. Methods. Patients with multiple recurrences of WDTC were retrospectively identified from the thyroid cancer database at Mount Sinai Hospital, Toronto (1963-2000). Data on patient, tumor, and recurrence characteristics were collected, and each patient was given aMACIS score. Results. A total of 31 patients were identified (11 male, 20 female; 16-83 years). Using univariate analysis, age > 45, stage III / IV disease, distant metastasis, vascular invasion, MACIS score > 6, and time to recurrence of < 12 months were found to be significant predictors for mortality in this subgroup. Conclusions. Patients with multiple recurrences of WDTC follow a distinct clinical course, marked with multiple treatment failures and a substantial risk of mortality. Copyright © 2009 Theresa Holler et al.
- Published
- 2009
24. Sinonasal undifferentiated carcinoma
- Author
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Kerrebijn, JDF, Tietze, L, Mock, D, Freeman, JL, and Otorhinolaryngology and Head and Neck Surgery
- Published
- 1998
25. Facial nerve reconstruction: outcome and failures
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Kerrebijn, JDF, Freeman, JL, and Otorhinolaryngology and Head and Neck Surgery
- Published
- 1998
26. Gelastic seizures. : In: Epilepsi: A comprehensive
- Author
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Freeman, JL, Eeg-Olofsson, O, Freeman, JL, and Eeg-Olofsson, O
- Published
- 2007
27. Hypothalamic hamartoma and gelastic seizures.
- Author
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Harvey, AS, Eeg-Olofsson, O, Freeman, JL, Harvey, AS, Eeg-Olofsson, O, and Freeman, JL
- Published
- 2007
28. Definition of the zebrafish genome using flow cytometry and cytogenetic mapping
- Author
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Freeman, JL, Adeniyi, A, Banerjee, R, Dallaire, S, Maguire, SF, Chi, J, Ng, BL, Zepeda, C, Scott, CE, Humphray, S, Rogers, J, Zhou, Y, Zon, LI, Carter, NP, Yang, F, Lee, C, Freeman, JL, Adeniyi, A, Banerjee, R, Dallaire, S, Maguire, SF, Chi, J, Ng, BL, Zepeda, C, Scott, CE, Humphray, S, Rogers, J, Zhou, Y, Zon, LI, Carter, NP, Yang, F, and Lee, C
- Abstract
BACKGROUND: The zebrafish (Danio rerio) is an important vertebrate model organism system for biomedical research. The syntenic conservation between the zebrafish and human genome allows one to investigate the function of human genes using the zebrafish model. To facilitate analysis of the zebrafish genome, genetic maps have been constructed and sequence annotation of a reference zebrafish genome is ongoing. However, the duplicative nature of teleost genomes, including the zebrafish, complicates accurate assembly and annotation of a representative genome sequence. Cytogenetic approaches provide "anchors" that can be integrated with accumulating genomic data. RESULTS: Here, we cytogenetically define the zebrafish genome by first estimating the size of each linkage group (LG) chromosome using flow cytometry, followed by the cytogenetic mapping of 575 bacterial artificial chromosome (BAC) clones onto metaphase chromosomes. Of the 575 BAC clones, 544 clones localized to apparently unique chromosomal locations. 93.8% of these clones were assigned to a specific LG chromosome location using fluorescence in situ hybridization (FISH) and compared to the LG chromosome assignment reported in the zebrafish genome databases. Thirty-one BAC clones localized to multiple chromosomal locations in several different hybridization patterns. From these data, a refined second generation probe panel for each LG chromosome was also constructed. CONCLUSION: The chromosomal mapping of the 575 large-insert DNA clones allows for these clones to be integrated into existing zebrafish mapping data. An accurately annotated zebrafish reference genome serves as a valuable resource for investigating the molecular basis of human diseases using zebrafish mutant models.
- Published
- 2007
29. Intrinsic epileptogenicity of cortical tubers revealed by intracranial EEG monitoring.
- Author
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Mohamed AR, Bailey CA, Freeman JL, Maixner W, Jackson GD, and Harvey AS
- Published
- 2012
- Full Text
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30. Radioiodine ablation in low-risk thyroid cancer.
- Author
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Orlov S, Freeman JL, Walfish PG, Orlov, Steven, Freeman, Jeremy L, and Walfish, Paul G
- Published
- 2012
- Full Text
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31. Efficacy and safety of central compartment neck dissection for recurrent thyroid carcinoma.
- Author
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Shah MD, Harris LD, Nassif RG, Kim D, Eski S, and Freeman JL
- Published
- 2012
32. De novo SCN1A mutations in migrating partial seizures of infancy.
- Author
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Carranza Rojo D, Hamiwka L, McMahon JM, Dibbens LM, Arsov T, Suls A, Stödberg T, Kelley K, Wirrell E, Appleton B, Mackay M, Freeman JL, Yendle SC, Berkovic SF, Bienvenu T, De Jonghe P, Thorburn DR, Mulley JC, Mefford HC, and Scheffer IE
- Published
- 2011
- Full Text
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33. Correlates of Bacterial Pneumonia Hospitalizations in Elders, Texas Border.
- Author
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Lemus FC, Tan A, Eschbach K, Freeman DH Jr., and Freeman JL
- Subjects
HOSPITAL care ,IMMUNIZATION ,PREVENTIVE medicine ,PNEUMONIA ,BACTERIAL diseases ,MEDICAL quality control ,AGE distribution ,BLACK people ,CONFIDENCE intervals ,EPIDEMIOLOGY ,HISPANIC Americans ,POISSON distribution ,RACE ,REGRESSION analysis ,RESEARCH funding ,WHITE people ,DATA analysis ,DATA analysis software ,DESCRIPTIVE statistics - Abstract
Background Immunization preventable bacterial pneumonia is an Agency for Healthcare Research and Quality (AHRQ) prevention quality indicator of health care. This study explored associations of individual and county correlates with bacterial pneumonia hospitalization rates for elders residing in 32 Texas counties bordering Mexico. Methods We estimated baseline rates from Texas Health Care Information Collection’s hospital discharge data for 1999–2001, and population counts from the 2000 U.S. Census. Results The rate among the total Texas border population was 500/10,000, three times the national rate. Elders 75+, males, and Latinos had the highest rates. An increase of 1 primary care physician per 1000 population is associated with a decrease in pneumonia-related hospitalization rates by 33%, while each 10% increase in Latinos is associated with a 0.1% rate increase. Discussion This baseline bacterial pneumonia hospitalization study demonstrates a systematic approach to estimate county rates, a process that could lead to improved outcomes through effective community interventions. Methodology demonstrates how publicly available hospital discharge data can be used by communities to better measure and improve quality of health care. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
34. Dissecting racial disparities in the treatment of patients with locoregional pancreatic cancer: a 2-step process.
- Author
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Riall TS, Townsend CM Jr, Kuo YF, Freeman JL, Goodwin JS, Riall, Taylor S, Townsend, Courtney M Jr, Kuo, Yong-Fang, Freeman, Jean L, and Goodwin, James S
- Abstract
Background: Previous studies have demonstrated that black patients with pancreatic cancer are less likely to undergo resection and have worse overall survival compared with white patients. The objective of this study was to determine whether these disparities occur at the point of surgical evaluation or after evaluation has taken place.Methods: The authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data (1992-2002) to compare black patients and white patients with locoregional pancreatic cancer in univariate models. Logistic regression was used to determine the effect of race on surgical evaluation and on surgical resection after evaluation. Cox proportional hazards models were used to identify which factors influenced 2-year survival.Results: Nine percent of 3777 patients were black. Blacks were substantially less likely than whites to undergo evaluation by a surgeon (odds ratio, 0.57; 95% confidence interval, 0.42-0.77) when the model was adjusted for demographics, tumor characteristics, surgical evaluation, socioeconomic status, and year of diagnosis. Patients who were younger and who had fewer comorbidities, abdominal imaging, and a primary care physician were more likely to undergo surgical evaluation. Once they were seen by a surgeon, blacks still were less likely than whites to undergo resection (odds ratio, 0.64; 95% confidence interval, 0.49-0.84). Although black patients had decreased survival in an unadjusted model, race no longer was significant after accounting for resection.Conclusions: Twenty-nine percent of black patients with potentially resectable pancreatic cancers never received surgical evaluation. Without surgical evaluation, patients cannot make an informed decision and will not be offered resection. Attaining higher rates of surgical evaluation in black patients would be the first step to eliminating the observed disparity in the resection rate. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
35. Risk of subsequent dementia diagnoses does not vary by types of adjuvant chemotherapy in older women with breast cancer.
- Author
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Raji MA, Tamborello LP, Kuo YF, Ju H, Freeman JL, Zhang DD, Giordano SH, Goodwin JS, Raji, Mukaila A, Tamborello, Lynsey P, Kuo, Yong-Fang, Ju, Hyunsu, Freeman, Jean L, Zhang, Dong D, Giordano, Sharon H, and Goodwin, James S
- Abstract
Objective: Little is known about long-term cognitive side effects of adjuvant chemotherapy for breast cancer. We thus examined incidence of dementia diagnoses in older women diagnosed with breast cancer, stratified by types of chemotherapy regimen.Methods: We identified patients with incident dementia diagnoses through Medicare claims linked to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor registry data. The study population (n = 6,932) consisted of women at least 68 years of age, who were diagnosed with early-stage breast cancer from 1994 through 2002 in one of the SEER areas and received chemotherapy as part of their cancer treatment. Excluded were women with a diagnosis of dementia within the 3 years prior to their cancer diagnosis.Results: Our sample comprised mostly white women. The mean age was 74. Fifty-seven percent were estrogen receptor positive. Over 70% had no comorbidity. The use of taxol and anthracycline-based treatments increased from mid-1990s to early 2000. Increasing age at cancer diagnosis, Black ethnicity, living in a census tract with lower level of education, and increasing number of comorbidities were associated with new claims of dementia diagnoses after chemotherapy. There was no significant association between types of chemotherapy agents and risk of subsequent dementia diagnoses.Conclusion: No association was found between types of adjuvant chemotherapy agents for breast cancer and risk of new dementia diagnoses. Our findings suggest that concerns about post-chemotherapy dementia should not be a major factor in determining type of adjuvant chemotherapy regimen to prescribe for older women with breast cancer. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
36. Ethnic differences in in-hospital place of death among older adults in California: effects of individual and contextual characteristics and medical resource supply.
- Author
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Lackan NA, Eschbach K, Stimpson JP, Freeman JL, Goodwin JS, Lackan, Nuha A, Eschbach, Karl, Stimpson, Jim P, Freeman, Jean L, and Goodwin, James S
- Published
- 2009
- Full Text
- View/download PDF
37. Mammography use may partially mediate disparities in tumor size at diagnosis in women with Social Security Disabilities.
- Author
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Caban ME, Kuo Y, Mahnken JD, Nosek MA, and Freeman JL
- Abstract
Objective: This study determined the association between screening mammography and tumor size at diagnosis in older women whose original reason for entitlement to Medicare benefits was disability (SSDI). Methods: A retrospective study of female Medicare beneficiaries older than 69 years diagnosed with breast cancer using Surveillance Epidemiological End Results (SEER)-Medicare linked database. Multiple linear regression techniques were used to determine the effect of screening mammography use on tumor size. Main Findings: The total number of women was 413 with SSDI and 8,989 without. Bivariate analysis showed that significantly fewer women with SSDI used screening mammography (45% vs. 38%, P = 0.0006) during the two years prior to diagnosis. Mean tumor size at diagnosis was 2.91 mm (95%, CI = 1.10, 4.73) larger in the group with SSDI. Conclusion: This study found that older women whose original reason for Medicare benefits was disability present with larger tumors at breast cancer diagnosis compared to those who were not. Screening mammography may partially mediate the disparity. [ABSTRACT FROM AUTHOR]
- Published
- 2007
38. Extrathyroidal extension in well-differentiated thyroid cancer: macroscopic vs microscopic as a predictor of outcome.
- Author
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Hu A, Clark J, Payne RJ, Eski S, Walfish PG, and Freeman JL
- Published
- 2007
39. Fine-needle aspiration biopsy of the thyroid: atypical cytopathological features.
- Author
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Yehuda M, Payne RJ, Seaberg RM, MacMillan C, and Freeman JL
- Published
- 2007
- Full Text
- View/download PDF
40. Mammography use among older Mexican-American women: correcting for over-reports of breast cancer screening.
- Author
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Mahnken JD, Freeman DJ Jr., DiNuzzo AR, and Freeman JL
- Abstract
OBJECTIVES: To determine the accuracy of self-reported mammography use and generate a correction factor that adjusts for reporting errors among Mexican-American women. DESIGN: Self-reported mammography use was compared with a medical chart review. PARTICIPANTS: A random sample of 199 Mexican-American women aged 50-74 in southeast Texas. MAIN OUTCOME MEASURES: Self-reported mammography use for the preceding 2 years and mammography use determined by medical chart review. RESULTS: Positive and negative predictive values of mammography self-reports in the previous 2 years were 73.9 and 86.0%, respectively. The correction factor was 79.6%, or approximately 80% of the self-reported mammograms within the preceding 2 years could be verified through medical chart reviews. CONCLUSIONS: Mammography use rates among Mexican-American women were not as high as self-reports indicated. Estimates need to be adjusted downward by approximately 20%. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
41. Three-week thyroxine withdrawal: a thyroid-specific quality of life study.
- Author
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Davids T, Witterick IJ, Eski S, Walfish PG, and Freeman JL
- Published
- 2006
42. Prognostic variables and calcitonin in medullary thyroid cancer.
- Author
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Clark JR, Fridman TR, Odell MJ, Brierley J, Walfish PG, and Freeman JL
- Published
- 2005
43. Familial non-medullary thyroid cancer: a matched-case control study.
- Author
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Maxwell EL, Hall FT, and Freeman JL
- Published
- 2004
44. Prognostic factors in well-differentiated thyroid carcinoma.
- Author
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Cushing SL, Palme CE, Audet N, Eski S, Walfish PG, and Freeman JL
- Published
- 2004
45. Decreasing variation in the use of hospice among older adults with breast, colorectal, lung, and prostate cancer.
- Author
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Lackan NA, Ostir GV, Freeman JL, Mahnken JD, and Goodwin JS
- Abstract
BACKGROUND: Utilization of hospice services has been shown to vary by place of residence and patient characteristics. OBJECTIVES: The purpose of this study was to examine whether such variation has changed over time. Hospice utilization is examined as a function of sociodemographic characteristics, geographic location, type of insurance, and year of death. RESEARCH DESIGN: This study used a retrospective cohort design. SUBJECTS: We used data from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database to study hospice utilization in subjects aged 67 and older diagnosed with breast, colorectal, lung, or prostate cancer from 1991 to 1996 and who died between 1991 and 1999. RESULTS: Of the 170,136 subjects aged 67 and older who died from 1991 through 1999, 51,345 (30.2%) were enrolled in hospice before they died. Hospice utilization varied significantly by patient characteristics, including type of insurance, age, marital status, race and ethnicity, gender, urban versus rural residence, type of cancer, income level, and education level. This variation, however, decreased over time for subgroups defined by type of insurance, marital status, urban residence, and income. Variation in hospice use increased over time as a function of age and type of cancer. There was no change in variation in use in blacks compared with non-Hispanic whites over time. CONCLUSIONS: The variation in hospice use by several patient characteristics is decreasing over time, a finding consistent with the manner in which new medical technologies diffuse. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
46. Clinical course of thyroid carcinoma after neck dissection.
- Author
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Shah MD, Hall FT, Eski SJ, Witterick IJ, Walfish PG, and Freeman JL
- Published
- 2003
47. Generalized epilepsy in hypothalamic hamartoma: evolution and postoperative resolution.
- Author
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Freeman JL, Harvey AS, Rosenfeld JV, Wrennall JA, Bailey CA, Berkovic SF, Freeman, J L, Harvey, A S, Rosenfeld, J V, Wrennall, J A, Bailey, C A, and Berkovic, S F
- Published
- 2003
- Full Text
- View/download PDF
48. Measuring the performance of screening mammography in community practice with Medicare claims data.
- Author
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Freeman JL, Goodwin JS, Zhang D, Nattinger AB, and Freeman DH Jr.
- Abstract
BACKGROUND: Few studies have examined the outcomes of screening mammography in community practice, particularly the extent of false positive exams among older asymptomatic women. RESEARCH DESIGN: Subjects were female Medicare beneficiaries, age 67 or older, residing in one of eleven SEER areas, with no evidence of breast cancer. Medicare claims data were used to identify their screening mammograms over two time periods, 1993-1995 and 1996-1998, and to measure their use of follow-up diagnostic testing (diagnostic mammography, breast ultrasound and breast biopsy) within three months of the screening mammogram. RESULTS: There were significant differences among the rates of diagnostic testing for each age group (67-74; 75+ ) by year, but no clear trend toward higher or lower rates over time. Although rates of diagnostic testing differed significantly by geographic region in both time periods 1993-1995 and 1996-1998, estimates of specificity for all regions were within AHRQ clinical practice guidelines (specificity greater than 90%). Specificity significantly improved with the volume of the radiologist's practice for the latter time period (1996-1998) but not for the former (1993-1995). CONCLUSION: Medicare claims offer an accessible population-based source of data for mammography performance indicators. As such, they offer a low cost method for evaluating individual mammography practices as well as monitoring the impact of reimbursement policies, practice guidelines and laws mandating requirements for accrediting facilities. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
49. Predictive value of serum thyroglobulin after surgery for thyroid carcinoma.
- Author
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Hall FT, Beasley NJ, Eski SJ, Witterick IJ, Walfish PG, and Freeman JL
- Published
- 2003
50. Pap smear use in a population of older Mexican-American women.
- Author
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Randolph WM, Freeman DH Jr., and Freeman JL
- Abstract
BACKGROUND: Hispanic women and older women (age > or = 50 years) in general have been identified as populations of women who often underutilize Papanicolaou (Pap) smears. OBJECTIVE: To report the rates of cervical cancer screening in a group of older Mexican American women and to identify the correlates of having a Pap smear in the past three years. DATA SOURCE: The Mammography Use by Older Mexican-American Women Survey, a stratified area probability sample of 452 women ages 50-74 from three southeast Texas counties. Self-report data was collected with in-person interviews from 1997 to 1999. RESULTS: We found that 93.1% of the women reported at least one Pap smear in their lifetime and that 64.1% reported a Pap smear in the past three years. Odds of reporting a recent Pap smear was lower for older women (OR 0.51, 95% CI 0.32-0.82) and those below the poverty line (OR 0.52, 95% CI 0.33-0.82). The odds were higher for women who had a regular doctor for female care (OR 6.49, 95% CI 2.96-14.23) or a regular clinic or hospital source for female care (OR 5.50, 95% CI 2.55-11.89). Among these older Mexican-American women, cultural factors (language of interview, acculturation, fatalism) did not have a significant effect on screening use. CONCLUSION: Recent Pap smear use (64.1%) falls well below the year 2010 goal of 90%. Efforts need to be made to overcome barriers to Pap smear utilization for these women, such as providing access to female medical care. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
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