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5 The Impact of Sex and Associations With Treatment Exposures on Neurocognitive Impairment in Pediatric Cancer Survivors: A report from the Childhood Cancer Survivor Study
- Rachel K Peterson, Yan Chen, Kevin Oeffinger, Yutaka Yasui, Wendy Leisenring, Gregory T Armstrong, Leslie L Robison, Rebecca M Howell, Sogol Mostoufi-Moab, Jordan Gilleland Marchak, Kevin R. Krull, Kim Edelstein
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 315-316
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Objective:
Sexual dimorphism in human brain structure and behavior is influenced by exposure to sex hormones during critical developmental periods. In children, cancer and cancer treatments may alter hormone activity and brain development, impacting neurocognitive functions.
Participants and Methods:Five-year survivors of childhood cancer (N=15,560) diagnosed at <21 years from 1970 to 1999, and 3,206 siblings from the Childhood Cancer Survivor Study completed the Neurocognitive Questionnaire (NCQ), a measure of self-reported task efficiency (TE), emotion regulation (ER), Organization, and working memory (WM). We compared rates of cognitive impairment (i.e., NCQ scores >90th percentile) in survivors and same-sex siblings, and sex differences in risk factors for cognitive impairment (i.e., treatment exposures, chronic health conditions (CHCs), cancer diagnosis, age at diagnosis) using modified Poisson regressions.
Results:Survivors were more likely to report cognitive impairment than same-sex siblings (Males: TE OR=2.3, p<.001; ER OR=1.7, p=.008; Organization OR=1.5, p=.04; WM OR=2.3, p<.001. Females: TE OR=2.6, p<.001; ER OR=1.9, p<.001; Organization OR=1.5, p=.02; WM OR=2.6, p<.001). Within survivors, females were more likely than males to report impairment in TE (OR=1.2, p=.001), ER (OR=1.5, p<.001), and WM (OR=1.2, p<.001). There were no sex differences in symptom severity in siblings (all ps>.05). Risk factors for cognitive impairment in survivors included cranial radiation dose (TE <20Gy OR=1.5, p=.008, ≥20Gy OR=2.5, p<.001; ER OR=1.5, p<.001; Organization <20 Gy OR=1.4, p<.001; < WM 20 Gy OR=1.8, p<.001, ≥20Gy OR=2.7, p<.001), presence of moderate to severe CHCs (TE 1 CHC OR=1.9, p<.001, >1 CHC OR=3.6, p<.001; ER 1 CHC OR=1.7, p<.001, >1 CHC OR=2.2, p<.001; Organization 1 CHC OR=1.5, p=.001, >1 CHC OR=2.5, p<.001; WM 1 CHC OR=1.8, p<.001, >1 CHC OR=4.1, p<.001). There were sex differences in cognitive impairment risk factors in survivors. In females, cranial radiation dose (<20 Gy TE OR=1.6, p=.02; ≥20Gy TE OR=1.4, p=.01), leukemia diagnosis (TE OR=1.4, p=.02), or diagnosis age between 3-5 years (WM OR=1.4, p=.02) conferred higher risk for cognitive impairment compared to males with the same history. Females diagnosed with Hodgkin’s lymphoma (Organization OR=0.61, p=.05) or non-Hodgkin’s lymphoma (Organization OR=0.55, p=.03) were at lower risk for cognitive impairment compared to males.
Conclusions:We found sex-specific differences in rates of, and risk factors for, neurocognitive impairment, suggesting a sex vulnerability. Future studies examining interactions between sex hormones and treatment exposures during brain development will enable tailoring treatments follow-up interventions to ensure that quality of life is maximized.
Clinical impact of antipsychotic and benzodiazepine reduction: findings from a multicomponent psychotropic reduction program within long-term aged care
- Daniel J. Hoyle, Gregory M. Peterson, Ivan K. Bindoff, Lisa M. Clinnick, Aidan D. Bindoff, Juanita L. Breen
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- Journal:
- International Psychogeriatrics / Volume 33 / Issue 6 / June 2021
- Published online by Cambridge University Press:
- 18 June 2020, pp. 587-599
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Objectives:
To explore the relationships between dose changes to antipsychotic and/or benzodiazepine medications and resident outcomes, including variations in neuropsychiatric symptoms, quality of life (QoL), and social withdrawal, within a multicomponent, interdisciplinary antipsychotic and benzodiazepine dose reduction program.
Design:Prospective, observational, longitudinal study.
Intervention:The Reducing Use of Sedatives (RedUSe) project involved 150 Australian Long-Term Care Facilities (LTCFs) incorporating auditing and benchmarking of prescribing, education, and multidisciplinary sedative reviews.
Setting:A convenience sample of LTCFs (n = 28) involved in RedUSe between January 2015 and March 2016.
Participants:Permanent residents (n = 206) of LTCFs involved in RedUSe taking an antipsychotic and/or benzodiazepine daily. Residents were excluded if they had a severe psychiatric condition where antipsychotic therapy should generally be maintained long-term (e.g., bipolar disorder, schizophrenia) or were considered end-stage palliative.
Measurements:Neuropsychiatric symptoms (Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory (CMAI)), QoL (Assessment of Quality of Life-4D), and social withdrawal (Multidimensional Observation Scale for Elderly Subjects-withdrawal subscale) were measured at baseline and 4 months where nursing staff completed psychometric tests as proxy raters.
Results:There was no evidence that psychometric measures were worsened following dose reductions. In fact, dose reduction was associated with small, albeit non-statistically significant, improvements in behavior, particularly less physically non-aggressive behavior with both drug groups (−0.36 points per 10% reduction in antipsychotic dose, −0.17 per 10% reduction in benzodiazepine dose) and verbally agitated behavior with benzodiazepine reduction (−0.16 per 10% dose reduction), as measured with the CMAI. Furthermore, antipsychotic reduction was associated with non-statistically significant improvements in QoL and social withdrawal.
Conclusions:Antipsychotic and benzodiazepine dose reduction in LTCFs was not associated with deterioration in neuropsychiatric symptoms, QoL, or social withdrawal. Trends toward improved agitation with antipsychotic and benzodiazepine dose reduction require further evaluation in larger, prospective, controlled studies.
Smoking cessation and the general practice pharmacist
- Louise S Deeks, Sam Kosari, Anne Develin, Gregory M. Peterson, Mark Naunton
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- Journal:
- Journal of Smoking Cessation / Volume 14 / Issue 3 / September 2019
- Published online by Cambridge University Press:
- 05 April 2019, pp. 186-189
- Print publication:
- September 2019
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Introduction
Roles for pharmacists in general practice are developing in Australia. It is known that pharmacists can provide effective smoking cessation services in other settings but evidence in general practice is lacking.
AimTo determine whether a pharmacist can provide effective smoking cessation services within general practice.
MethodData from smoking cessation consultations were obtained for 66 consecutive patients seen by one practice pharmacist. The pharmacist tailored interventions to the individual. Medication was offered in collaboration with community pharmacists and general practitioners. Quit coaching, based on motivational interviewing, was conducted. Smoking status was ascertained at least 6 months after the intended quit date and verified by a carbon monoxide breath test where possible.
ResultsThe patients’ median age was 43 years (range 19–74 years); 42 were females (64%). At baseline, the median (i) number of pack years smoked was 20 (range: 1–75); (ii) Fagerstrom Test of dependence score was 6 (1–10); and (iii) number of previous quit attempts was 3 (0–10). Follow-up after at least 6 months determined a self-reported point prevalence abstinence rate of 30% (20/66). Of all patients who reported to be abstinent, 65% (13/20) were tested for carbon monoxide breath levels and were all below 7 ppm. The biochemically verified smoking abstinence rate was therefore 20% overall (13/66). Successful quit attempts were associated with varenicline recommendation (69% v 25%), increased median number of practice pharmacist consultations (4 v 2 per patient) and mental health diagnosis (85% v 51%).
ConclusionOur observed abstinence rate was comparable or better than those obtained by practice nurses, community pharmacists and outpatient pharmacists, indicating the general practice pharmacist provided an effective smoking cessation intervention. A larger randomised trial is warranted.
Contributors
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- By Lenard A. Adler, Pinky Agarwal, Rehan Ahmed, Jagga Rao Alluri, Fawaz Al-Mufti, Samuel Alperin, Michael Amoashiy, Michael Andary, David J. Anschel, Padmaja Aradhya, Vandana Aspen, Esther Baldinger, Jee Bang, George D. Baquis, John J. Barry, Jason J. S. Barton, Julius Bazan, Amanda R. Bedford, Marlene Behrmann, Lourdes Bello-Espinosa, Ajay Berdia, Alan R. Berger, Mark Beyer, Don C. Bienfang, Kevin M. Biglan, Thomas M. Boes, Paul W. Brazis, Jonathan L. Brisman, Jeffrey A. Brown, Scott E. Brown, Ryan R. Byrne, Rina Caprarella, Casey A. Chamberlain, Wan-Tsu W. Chang, Grace M. Charles, Jasvinder Chawla, David Clark, Todd J. Cohen, Joe Colombo, Howard Crystal, Vladimir Dadashev, Sarita B. Dave, Jean Robert Desrouleaux, Richard L. Doty, Robert Duarte, Jeffrey S. Durmer, Christyn M. Edmundson, Eric R. Eggenberger, Steven Ender, Noam Epstein, Alberto J. Espay, Alan B. Ettinger, Niloofar (Nelly) Faghani, Amtul Farheen, Edward Firouztale, Rod Foroozan, Anne L. Foundas, David Elliot Friedman, Deborah I. Friedman, Steven J. Frucht, Oded Gerber, Tal Gilboa, Martin Gizzi, Teneille G. Gofton, Louis J. Goodrich, Malcolm H. Gottesman, Varda Gross-Tsur, Deepak Grover, David A. Gudis, John J. Halperin, Maxim D. Hammer, Andrew R. Harrison, L. Anne Hayman, Galen V. Henderson, Steven Herskovitz, Caitlin Hoffman, Laryssa A. Huryn, Andres M. Kanner, Gary P. Kaplan, Bashar Katirji, Kenneth R. Kaufman, Annie Killoran, Nina Kirz, Gad E. Klein, Danielle G. Koby, Christopher P. Kogut, W. Curt LaFrance, Patrick J.M. Lavin, Susan W. Law, James L. Levenson, Richard B. Lipton, Glenn Lopate, Daniel J. Luciano, Reema Maindiratta, Robert M. Mallery, Georgios Manousakis, Alan Mazurek, Luis J. Mejico, Dragana Micic, Ali Mokhtarzadeh, Walter J. Molofsky, Heather E. Moss, Mark L. Moster, Manpreet Multani, Siddhartha Nadkarni, George C. Newman, Rolla Nuoman, Paul A. Nyquist, Gaia Donata Oggioni, Odi Oguh, Denis Ostrovskiy, Kristina Y. Pao, Juwen Park, Anastas F. Pass, Victoria S. Pelak, Jeffrey Peterson, John Pile-Spellman, Misha L. Pless, Gregory M. Pontone, Aparna M. Prabhu, Michael T. Pulley, Philip Ragone, Prajwal Rajappa, Venkat Ramani, Sindhu Ramchandren, Ritesh A. Ramdhani, Ramses Ribot, Heidi D. Riney, Diana Rojas-Soto, Michael Ronthal, Daniel M. Rosenbaum, David B. Rosenfield, Durga Roy, Michael J. Ruckenstein, Max C. Rudansky, Eva Sahay, Friedhelm Sandbrink, Jade S. Schiffman, Angela Scicutella, Maroun T. Semaan, Robert C. Sergott, Aashit K. Shah, David M. Shaw, Amit M. Shelat, Claire A. Sheldon, Anant M. Shenoy, Yelizaveta Sher, Jessica A. Shields, Tanya Simuni, Rajpaul Singh, Eric E. Smouha, David Solomon, Mehri Songhorian, Steven A. Sparr, Egilius L. H. Spierings, Eve G. Spratt, Beth Stein, S.H. Subramony, Rosa Ana Tang, Cara Tannenbaum, Hakan Tekeli, Amanda J. Thompson, Michael J. Thorpy, Matthew J. Thurtell, Pedro J. Torrico, Ira M. Turner, Scott Uretsky, Ruth H. Walker, Deborah M. Weisbrot, Michael A. Williams, Jacques Winter, Randall J. Wright, Jay Elliot Yasen, Shicong Ye, G. Bryan Young, Huiying Yu, Ryan J. Zehnder
- Edited by Alan B. Ettinger, Albert Einstein College of Medicine, New York, Deborah M. Weisbrot, State University of New York, Stony Brook
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- Book:
- Neurologic Differential Diagnosis
- Published online:
- 05 June 2014
- Print publication:
- 17 April 2014, pp xi-xx
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Generic Substitution of Antiepileptics: Need for a Balanced View
- Gregory M. Peterson
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- Journal:
- CNS Spectrums / Volume 16 / Issue 8 / August 2011
- Published online by Cambridge University Press:
- 01 August 2011, pp. 169-175
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There is considerable interest and debate concerning the place of generic substitution, especially relating to antiepileptic drugs (AEDs). Sadly, one of the causes of the ongoing debate is confusion, often intentionally fueled by the pharmaceutical industry among health professionals and patients regarding the regulatory determination of bioequivalence. Few understand the correct definition. It is often erroneously stated that to be considered bioequivalent there is an allowed difference in the extent and rate of absorption of 80% to 125% between a generic drug product and the branded standard. This is false and implies that there is a wide leniency allowed, with varying clinical outcomes probable. This myth needs to be countered to ensure the safety of patients. A balanced review of the issues surrounding the generic substitution of AEDs is presented.
Tem of Beo Aerosols: Materials Aspects of Method Development in Studying Chronic Beryllium Disease
- Robert M. Dickerson, Ronald C. Scripsick, Gregory A. Day, Aleksandr B. Stefaniak, Eric J. Peterson
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- Journal:
- Microscopy and Microanalysis / Volume 7 / Issue S2 / August 2001
- Published online by Cambridge University Press:
- 02 July 2020, pp. 482-483
- Print publication:
- August 2001
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The present work is a small portion of a multi-disciplinary science-based study of the physicochemical properties of respirable aerosols containing beryllium. The working hypothesis is that Chronic Beryllium Disease (CBD) is by controlled dissolution of Be particles in the lung. Recent studies have shown correlations between specific Be production processes and the development of Be sensitivity and CBD. in Beryllium Oxide (BeO) production, 9.8% of the workers develop a sensitivity to Be and 4.9% develop CBD. in vitro cellular dose-response relations have been observed for BeO particles.
This study involves a characterization of BeO materials sampled from the air stream around the production process at Brush Wellman Inc. (Elmore, OH) and laboratory-prepared BeO. One purpose of this work is to determine if lab-prepared material is a good surrogate for the process-generated aerosols for cellular dissolution studies. Both materials were size-separated into six fractions using a five-stage cyclone followed by a electrostatic precipitator (ESP).