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1.
Int J Eat Disord ; 56(1): 247-256, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36574733

RESUMEN

OBJECTIVE: The COVID-19 pandemic created significant challenges in accessing and receiving treatment for individuals with eating disorders (EDs). The purpose of this study is to explore perceptions of and experiences with ED treatment during the first year of the pandemic among individuals with past and self-reported EDs in the United States. METHODS: Online surveys were administered to adults (N = 510) with a past or current self-reported ED at 13 timepoints between April 2020 and May 2021. Using longitudinal qualitative analysis, 5651 free-text responses were examined to capture experiences with ED treatment and generate inferences of change over time. RESULTS: We categorized results into four sequential, temporal quarters and identified patterns that explained participants' perceptions of facilitators, barriers, and experiences with ED treatment over time: Quarter 1. Treatment Disruption and Reorienting Recovery; Quarter 2. Accumulating COVID-19 Stress and Virtual Treatment Woes; Quarter 3. A Continuation of Inadequate Care; and Quarter 4. Ongoing Adaptation and Adjustment to Uncertainty. Participant experiences were marked by numerous barriers to accessing care, challenges adjusting to virtual treatment, unmet treatment needs, and beginning acceptance of telehealth. DISCUSSION: Our findings present a timeline to help evaluate challenges related to navigating the switch to virtual care which created significant disruption to ED recovery. Participants spent much of the first year trying to adjust to unemployment, loss of insurance, and lack of access to in-person treatment. Future research should identify additional strategies to improve the receipt and experience of care for EDs. PUBLIC SIGNIFICANCE: Our findings suggest that individuals with eating disorders were significantly challenged by accumulating COVID-19 stress, worsening symptomatology, and limited access to effective treatment during the first year of the pandemic. This knowledge can guide clinicians, treatment centers, and policy makers in addressing the behavioral health needs of individuals impacted by disordered eating amidst emergent public health crises.


Asunto(s)
COVID-19 , Trastornos de Alimentación y de la Ingestión de Alimentos , Adulto , Humanos , Estados Unidos , Pandemias , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Encuestas y Cuestionarios , Autoinforme
2.
J Public Health Manag Pract ; 28(2): E518-E524, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34016911

RESUMEN

OBJECTIVE: To evaluate prescribers' reactions and self-reported intentions to change prescribing behavior in response to opioid-prescribing report cards. DESIGN: We surveyed a sample of licensed prescribers in the state of Colorado registered with the state's prescription drug monitoring program (PDMP). SETTING: In 2018, Colorado disseminated tailored opioid-prescribing report cards to increase use of the PDMP and improve opioid prescribing. Report cards reflected individual prescribing history and compared individuals with an aggregate of others in the same specialty. Surveys were sent to approximately 29 000 prescribers registered with the PDMP 12 weeks after report card distribution. If respondents were not sent a report card, they were shown a sample report. Respondents were asked about their perceptions of the usefulness of the information and intentions to change their prescribing. PARTICIPANTS: A total of 3784 prescribers responded to the survey. MAIN OUTCOME MEASURES: Respondents were asked about their attitudes and reactions to an opioid-prescribing report card. Answers were given in the form of a 5-point Likert scale or multiple-choice questions. RESULTS: Of those who responded, 53.6% were male and nearly half (49.5%) had spent more than 20 years in practice. Among prescribers who recalled receiving a report card, most felt the reports were easy to understand (87.4%) and provided new information (82.8%). Two-thirds of prescribers who saw their reports felt the information accurately reflected their prescribing practices. Overall, 40.0% reported they planned to change their prescribing behaviors as a result of the information provided. The most useful metrics identified by prescribers were the number of patients with multiple providers and the number of patients receiving dangerous combination therapy. CONCLUSIONS: Overall, perceptions of the usefulness and accuracy of the report cards were positive. Understanding how the reports are perceived is a key factor to their use and influence. Further tailoring of the report to prescribers of different specialties and experience may enhance the effectiveness of the report cards.


Asunto(s)
Mal Uso de Medicamentos de Venta con Receta , Programas de Monitoreo de Medicamentos Recetados , Analgésicos Opioides/uso terapéutico , Recolección de Datos , Humanos , Masculino , Pautas de la Práctica en Medicina
3.
J Pediatr Psychol ; 42(8): 815-822, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28369473

RESUMEN

Objective: Many pediatric chronic illnesses have shown increased survival rates, leading to greater focus on cognitive and psychosocial issues. Neuropsychological services have traditionally been provided only after significant changes in the child's cognitive or adaptive functioning have occurred. This model of care is at odds with preventative health practice, including early identification and intervention of neuropsychological changes related to medical illness. We propose a tiered model of neuropsychological evaluation aiming to provide a preventative, risk-adapted level of assessment service to individuals with medical conditions impacting the central nervous system based on public health and clinical decision-making care models. Methods: Elements of the proposed model have been used successfully in various pediatric medical populations. We summarize these studies in association with the proposed evaluative tiers in our model. Results and Conclusions: This model serves to inform interventions through the various levels of assessment, driven by evidence of need at the individual level in real time.


Asunto(s)
Enfermedades del Sistema Nervioso Central/diagnóstico , Pruebas Neuropsicológicas , Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/psicología , Niño , Enfermedad Crónica , Toma de Decisiones Clínicas , Humanos , Salud Pública
4.
Xenobiotica ; 45(1): 60-70, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25034010

RESUMEN

1. Plasma clearance of dolutegravir, an unboosted HIV-1 integrase inhibitor, was low in rat and monkey (0.23 and 2.12 mL/min/kg, respectively) as was the volume of distribution (0.1 and 0.28 L/kg, respectively) with terminal elimination half-life approximately 6 h. Dolutegravir was rapidly absorbed from oral solution with a high bioavailability in rat and monkey (75.6 and 87.0% respectively), but solubility or dissolution rate limited when administered as suspension. 2. Dolutegravir was highly bound (>99%) to serum proteins in rat and monkey, similar to binding to plasma and serum proteins in human. Radioactivity was associated with the plasma versus cellular components of blood across all species. 3. Following oral administration to rats, [(14)C]dolutegravir-related radioactivity was distributed to most tissues, due in part to high permeability; however, because of high plasma protein binding, tissue to blood ratios were low. In mouse, rat and monkey, the absorbed dose was extensively metabolized and secreted into bile, with the majority of the administered radioactivity eliminated in feces within 24 h. 4. The primary route of metabolism of dolutegravir was through the formation of an ether glucuronide. Additional biotransformation pathways: benzylic oxidation followed by hydrolysis to an N-dealkylated product, glucose conjugation, oxidative defluorination, and glutathione conjugation.


Asunto(s)
Inhibidores de Integrasa VIH/metabolismo , Compuestos Heterocíclicos con 3 Anillos/metabolismo , Animales , Bilis/química , Disponibilidad Biológica , Radioisótopos de Carbono , Femenino , Inhibidores de Integrasa VIH/análisis , Inhibidores de Integrasa VIH/farmacocinética , Compuestos Heterocíclicos con 3 Anillos/análisis , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Macaca fascicularis , Masculino , Ratones , Oxazinas , Piperazinas , Piridonas , Ratas Sprague-Dawley , Distribución Tisular
5.
Drug Alcohol Depend ; 256: 111099, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38306822

RESUMEN

BACKGROUND/AIM: Poor medication adherence is one of the main barriers to the long-term efficacy of buprenorphine/naloxone (BUP/NAL). The aims of this pilot investigation were to examine if a Bluetooth-enabled pill cap and mobile application is a feasible, usable tool for increasing BUP/NAL adherence among people with an opioid use disorder. METHODS: This pilot randomized clinical trial (RCT; total n = 41) lasted 12 weeks and was conducted in two office-based BUP/NAL provider locations in Spokane, WA and Coeur d'Alene, ID from January 2020 to September of 2021 with an 11-month gap due to COVID-19. Patients receiving BUP/NAL who consented to participate were randomized to receive the pill cap device (PLY group; n = 19) or a service as usual (SAU group; n = 22) group that included an identical but inactive cap for their bottle. The PLY group received reminders via text and voice, and the support of a "helper" (e.g., friend) to monitor pill cap openings. RESULTS: Most participants in PLY group found the device both feasible (92.86 %) and usable (78.57 %). Most participants liked using the device (92.86 %) and were satisfied with the device (85.71 %). While not statistically different from one another, medication adherence per the Medication Possession Ratio was 75 % in the SAU group and 84 % in the PLY group. Pill cap openings were significantly higher in the PLY group with an average of 91.8 openings versus the SAU group's average of 56.7 (p < 0.05). CONCLUSION: The devices was feasible, usable, and patients had high levels of satisfaction. The device was associated with increased pill openings.


Asunto(s)
Buprenorfina , Humanos , Buprenorfina/uso terapéutico , Estudios de Factibilidad , Proyectos Piloto , Combinación Buprenorfina y Naloxona , Cumplimiento de la Medicación
6.
Eat Behav ; 49: 101741, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37229948

RESUMEN

BACKGROUND/OBJECTIVE: Living in a food-insecure household may increase the risk for disordered eating. Though the Supplemental Nutrition Assistance Program (SNAP) was designed to reduce food insecurity, it may increase risk for disordered eating with the frequency in which benefits are distributed. Limited research has explored the lived experiences of managing eating behaviors while on SNAP, particularly among SNAP participants in larger bodies, and during COVID-19. Thus, the purpose of this study is to examine the experiences with eating behaviors among adults with a BMI ≥ 25 kg/m2, and who received SNAP benefits during the COVID-19 pandemic. METHODS: Eligible adults were recruited to participate in a semi-structured interview. Interviews were transcribed verbatim and analyzed using thematic analysis and content analysis. RESULTS: Participants (N = 16), had a mean (±SD) age of 43.4 ± 10.9 years, and overwhelmingly identified as female (86 %). One-third of the participants were Black. We identified 4 main themes: (1) not having enough money/benefits to cover needs; (2) navigating loss of control and emotional eating; (3) making sure the kids are alright; and (4) still feeling the pressure to manage weight. CONCLUSION: Managing eating behaviors while also navigating SNAP benefits is complex and may exacerbate risk of disordered eating.


Asunto(s)
COVID-19 , Asistencia Alimentaria , Adulto , Humanos , Femenino , Persona de Mediana Edad , Pandemias , Pobreza , Conducta Alimentaria
7.
JMIR Form Res ; 7: e40437, 2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37074780

RESUMEN

BACKGROUND: Opioid use disorders impact the health and well-being of millions of Americans. Buprenorphine and naloxone (BUP and NAL) can reduce opioid overdose deaths, decrease misuse, and improve quality of life. Unfortunately, poor medication adherence is a primary barrier to the long-term efficacy of BUP and NAL. OBJECTIVE: We aimed to examine patient feedback on current and potential features of a Bluetooth-enabled pill bottle cap and associated mobile app for patients prescribed BUP and NAL for an opioid use disorder, and to solicit recommendations for improvement to effectively and appropriately tailor the technology for people in treatment for opioid use disorder. METHODS: A convenience sample of patients at an opioid use disorder outpatient clinic were asked about medication adherence, opioid cravings, experience with technology, motivation for treatment, and their existent support system through a brief e-survey. Patients also provided detailed feedback on current features and features being considered for inclusion in a technology designed to increase medication adherence (eg, inclusion of a personal motivational factor, craving and stress tracking, incentives, and web-based coaching). Participants were asked to provide suggestions for improvement and considerations specifically applicable to people in treatment for opioid use disorder with BUP and NAL. RESULTS: Twenty people with an opioid use disorder who were prescribed BUP and NAL participated (mean age 34, SD 8.67 years; 65% female; 80% White). Participants selected the most useful, second-most useful, and least useful features presented; 42.1% of them indicated that motivational reminders would be most useful, followed by craving and stress tracking (26.3%) and web-based support forums (21.1%). Every participant indicated that they had at least 1 strong motivating factor for staying in treatment, and half (n=10) indicated children as that factor. All participants indicated that they had, at some point in their lives, the most extreme craving a person could have; however, 42.1% indicated that they had no cravings in the last month. Most respondents (73.7%) stated that tracking cravings would be helpful. Most respondents (84.2%) also indicated that they believed reinforcers or prizes would help them achieve their treatment goals. Additionally, 94.7% of respondents approved of adherence tracking to accommodate this feature using smart packaging, and 78.9% of them approved of selfie videos of them taking their medication. CONCLUSIONS: Engaging patients taking treatment for opioid use disorder with BUP and NAL allowed us to identify preferences and considerations that are unique to this treatment area. As the technology developer of the pill cap and associated mobile app is able to take into consideration or integrate these preferences and suggestions, the smart cap and associated mobile app will become tailored to this population and more useful for them, which may encourage patient use of the smart cap and associated mobile app.

8.
J Addict Med ; 16(3): 324-332, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34392255

RESUMEN

INTRODUCTION: Despite inconclusive evidence that prescription drug monitoring programs (PDMP) reduce opioid-related mortality, guidelines recommend PDMP review with opioid prescribing. Some reported barriers to use include time-consuming processes to obtain data and workflow disruptions. METHODS: We provided access to a PMDP-electronic health record (EHR) integrated program to 123 clinicians in one healthcare system. Remaining clinicians within the healthcare system and metropolitan area did not receive PDMP-EHR integration program access. We identified changes in opioid prescribing by linking prescription data available in the state PMDP database to individual clinicians. The primary outcome was change in receipt of high dose opioid prescriptions (>90 mg morphine equivalents) by Colorado residents before and after program integration. Secondary outcomes included changes in long-acting opioid receipt and overlapping opioid and benzodiazepine prescription days. Next, we surveyed clinicians to assess their perspectives on PDMP data acquisition before and after PDMP-EHR integration program access. RESULTS: High-dose opioid receipt decreased significantly across all 3 clinician groups [PDMP-EHR integration program access (27.6%, to 6.9%, P < 0.001); no program access in the same healthcare system (4.8% to 2.9%, P < 0.001), and no program access across the metropolitan area (13.5% to 6.1%, P < 0.001)]. Clinicians reported improved access to PDMP data using the PDMP-EHR integrated program compared to the state PDMP website (98.6%). CONCLUSIONS: Further study of PDMP-EHR integration programs on patient and clinician outcomes may illuminate the role of this technology in public health and in clinical practice.


Asunto(s)
Analgésicos Opioides , Sistemas de Apoyo a Decisiones Clínicas , Analgésicos Opioides/uso terapéutico , Benzodiazepinas/uso terapéutico , Registros Electrónicos de Salud , Humanos , Morfolinas , Pautas de la Práctica en Medicina
9.
Xenobiotica ; 41(6): 464-75, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21370990

RESUMEN

A model that predicts human metabolism and disposition of drug candidates would be of value in early drug development. In this study, a chimeric (uPA+/+)/SCID mouse model was evaluated with three structurally distinct compounds (GW695634, a benzophenone, SB-406725, a tetrahydroisoquinoline and GW823093, a fluoropyrrolidine) for which human metabolism and disposition was characterized. Human metabolite profiles in plasma and/or urine were compared to those of chimeric (uPA+/+)/SCID and control CD-1 or (uPA+/+)/SCID) mice. GW695634 and SB-406725 exhibited primarily hepatic metabolism and were chosen as probes to assess which human metabolites would likely circulate systemically. GW823093 exhibited a combination of hepatic and extrahepatic metabolism such that renal excretion of drug-related material was ~2-fold greater in humans than in mice, and thus chosen as a probe to assess if the chimeric (uPA+/+)/SCID mouse would predict the urinary excretion of human metabolites. We observed that human metabolism and disposition was well represented for GW695634, somewhat represented for GW823093 and minimally represented for SB-406725. Collectively, the results of this and other studies suggest that while limitations for prediction of human metabolism and disposition exist, humanized chimeric mouse models can potentially represent informative new tools in drug discovery and development.


Asunto(s)
Quimera/metabolismo , Hígado/metabolismo , Modelos Biológicos , Preparaciones Farmacéuticas/metabolismo , Animales , Benzofenonas/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones SCID , Fenilalanina/análogos & derivados , Fenilalanina/metabolismo , Pirrolidinas/metabolismo , Sulfonamidas/metabolismo , Tetrahidroisoquinolinas/metabolismo
10.
Immunology ; 128(1 Suppl): e376-84, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19175792

RESUMEN

We investigated the role of two repressors of translation initiation in granulocytic differentiation using mice with a null mutation in the 4E-BP1 gene or with a null mutation in the 4E-BP2 gene. We show that 4E-BP1(-/-) and 4E-BP2(-/-) mice exhibit an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements compared with wild-type mice, which is suggestive of an impaired granulocytic differentiation. Clonogenetic analyses revealed a reduced number of granulocytic colonies and concomitant increase in granulo-monocytic colonies in 4E-BP(-/-) mice. Finally, a slight expansion of monocytic cells was observed in the 4E-BP2(-/-) mice. In contrast, we did not observe any significant difference in thymocyte maturation in these mice. These results, together with the fact that 4E-BPs are markedly induced during granulo-monocytic differentiation of myeloid cells in vitro, highlight the pivotal role of 4E-BP1 and 4E-BP2 in the early phases of myelopoiesis. These results represent the first in vivo evidence of the involvement of translation in the early phases of granulo-monocytic differentiation and further extend the role of translation in haematopoietic differentiation.


Asunto(s)
Proteínas Portadoras/inmunología , Diferenciación Celular/inmunología , Factores Eucarióticos de Iniciación/inmunología , Granulocitos/inmunología , Mielopoyesis/inmunología , Fosfoproteínas/inmunología , Proteínas Adaptadoras Transductoras de Señales , Animales , Médula Ósea/inmunología , Médula Ósea/metabolismo , Proteínas Portadoras/genética , Proteínas de Ciclo Celular , Factores Eucarióticos de Iniciación/genética , Granulocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Monocitos/inmunología , Monocitos/metabolismo , Fosfoproteínas/genética , Bazo/inmunología , Bazo/metabolismo , Células Madre/inmunología , Células Madre/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Timo/inmunología , Timo/metabolismo
11.
Drug Metab Dispos ; 37(2): 439-42, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19056914

RESUMEN

Lapatinib is a tyrosine kinase inhibitor approved for use in combination with capecitabine to treat advanced or metastatic breast cancers overexpressing human epidermal receptor 2 (ErbB2). This work investigated the role of P-glycoprotein (Pgp; the protein from the Mdr1a/b gene) and breast cancer resistance protein (Bcrp; the protein from the Bcrp1 gene) in modulating the central nervous system penetration of lapatinib at steady-state conditions in FVBn mice (wild-type), Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)/Bcrp1(-/-) knockout mice. After an intravenous infusion of lapatinib for 24 h to a targeted steady-state plasma concentration of 700 ng/ml (0.3 mg/kg/h) or 7000 ng/ml (3 mg/kg/h), lapatinib brain-to-plasma ratios were approximately 3- to 4-fold higher in Mdr1a/b(-/-) knockout mice (ratio range from 0.09 to 0.16) compared with wild-type mice (ratio range from 0.03 to 0.04). There was no difference in the brain-to-plasma ratio in the Bcrp1(-/-) knockout mice (ratio range from 0.03 to 0.04) compared with wild-type mice. In contrast, Mdr1a/b(-/-)/Bcrp1(-/-) triple knockout mice had a 40-fold higher brain-to-plasma ratio (ratio range from 1.2 to 1.7), suggesting that Pgp and Bcrp work in concert to limit the brain-to-plasma ratio of lapatinib in mice. This finding has important potential consequences for the treatment of brain tumors in breast cancer patients treated with tyrosine kinase inhibitors as well as the basic understanding of ATP binding cassette transporters expressed in the blood-brain barrier on the central nervous system disposition of drugs.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Transporte Biológico/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Quinazolinas/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/efectos de los fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/fisiología , Transportadoras de Casetes de Unión a ATP/genética , Animales , Antineoplásicos/uso terapéutico , Área Bajo la Curva , Transporte Biológico/fisiología , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Sistema Nervioso Central/metabolismo , Cricetinae , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Femenino , Humanos , Lapatinib , Masculino , Ratones , Ratones Noqueados , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/química , Receptor ErbB-2/metabolismo , Distribución Tisular
12.
Arch Phys Med Rehabil ; 90(7): 1170-5, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19577030

RESUMEN

OBJECTIVE: To examine the effects of acute fatigue of the hip abductors on the control of balance in young and older women. DESIGN: Pretest-posttest. SETTING: University research laboratory. PARTICIPANTS: Healthy young women (n=20; age, 23.0+/-1.5y; height, 166.52+/-4.5 cm; mass, 65.33+/-10.5 kg) and community-dwelling older women (n=20; age, 71.65+/-7.2y; height, 162.31+/-3.8 cm; mass, 71.16+/-11.6 kg) without a fall history. INTERVENTION: Measurements of control of single-limb balance before and after fatiguing the hip abductors of the dominant leg. MAIN OUTCOME MEASURE: Performance on 3 clinical assessments of control of balance: the modified Functional Reach Test in the forward, left, and right directions; the Lower-Extremity Reach Test in forward and lateral directions; and the Single-Limb Stance Time Test (SLSTT). RESULTS: Although the younger subjects showed a significantly greater control of balance than the older women in most tests, control of balance after acute fatigue failed to show a significant decline in either age group. The only exception to this was the SLSTT in the younger women in whom a significant 26% decline was noted (P<.05). CONCLUSIONS: Acute fatigue of the hip abductors did not result in a decreased control of balance in healthy young or older women without fall history. Despite considerable changes in movement strategies used to complete the postfatigue tests of balance, quantitative measures of balance did not decrease.


Asunto(s)
Envejecimiento/fisiología , Fatiga/fisiopatología , Cadera , Equilibrio Postural/fisiología , Enfermedad Aguda , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Variaciones Dependientes del Observador , Rango del Movimiento Articular
13.
Drug Metab Dispos ; 36(4): 695-701, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18216274

RESUMEN

Lapatinib [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine, GW572016, Tykerb] is a tyrosine kinase inhibitor approved for use in combination with capecitabine to treat advanced or metastatic breast cancers overexpressing HER2 (ErbB2). In this work we investigated the role of efflux and uptake transporters in lapatinib disposition and drug interactions. In vitro studies evaluated whether lapatinib is a substrate for efflux transporters or an inhibitor of efflux/uptake transporters. In vivo studies included whole-body autoradiography and an evaluation of the role of efflux transporters on the intestinal absorption and brain penetration of lapatinib using chemical or genetic knockout animals. Lapatinib is a substrate for the efflux transporters P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP). Furthermore, lapatinib is an inhibitor (IC(50) values 0.025-5 muM) of Pgp, BCRP, and organic anion transporting polypeptide 1B1 (a hepatic uptake transporter). In contrast, lapatinib yielded little inhibition on renal transporters (organic anion transporters, organic cation transporters, and uric acid transporter). In vivo studies demonstrated that brain concentrations of lapatinib were low and influenced by efflux transporters at the blood-brain barrier. In contrast, systemic exposure of lapatinib after oral dosing was unchanged when efflux by Pgp and BCRP was absent from the gastrointestinal tract. These in vitro and in vivo preclinical investigations provide a mechanistic basis for elucidating clinical drug interactions.


Asunto(s)
Proteínas de Transporte de Membrana/metabolismo , Quinazolinas/metabolismo , Animales , Transporte Biológico/fisiología , Células CHO , Línea Celular , Cricetinae , Cricetulus , Perros , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas/fisiología , Humanos , Lapatinib , Masculino , Proteínas de Transporte de Membrana/genética , Ratones , Ratones Mutantes , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Quinazolinas/química , Ratas , Ratas Wistar , Distribución Tisular/fisiología
15.
Child Neuropsychol ; 22(5): 509-36, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26070928

RESUMEN

A robust literature has developed documenting neurocognitive late effects in survivors of leukemia and central nervous system (CNS) tumors, the most frequent cancer diagnoses of childhood. Patterns of late effects include deficits in attention and concentration, working memory, processing speed, and executive function, as well as other domains. As childhood cancer survivors are living longer, ameliorating deficits both in broad and specific neurocognitive domains has been increasingly recognized as an endeavor of paramount importance. Interventions to improve cognitive functioning were first applied to the field of pediatric oncology in the 1990s, based on strategies used effectively with adults who had sustained a traumatic brain injury (TBI). Compilation and modification of these techniques has led to the development of structured cognitive training programs, with the effectiveness and feasibility of such interventions currently an active area of research. Consequently, the purpose of this critical review is to: (1) review cognitive training programs intended to remediate or prevent neurocognitive deficits in pediatric cancer patients and survivors, (2) critically analyze training program strengths and weaknesses to inform practice, and (3) provide recommendations for future directions of clinical care and research.


Asunto(s)
Atención , Cognición , Terapia Cognitivo-Conductual/educación , Memoria a Corto Plazo , Neoplasias/rehabilitación , Sobrevivientes/psicología , Adulto , Niño , Función Ejecutiva , Humanos , Neoplasias/psicología , Neuropsicología , Pediatría
16.
J Biomol Struct Dyn ; 23(2): 113-24, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16060685

RESUMEN

The transient secondary structure and dynamics of an intrinsically unstructured linker domain from the 70 kDa subunit of human replication protein A was investigated using solution state NMR. Stable secondary structure, inferred from large secondary chemical shifts, was observed for a segment of the intrinsically unstructured linker domain when it is attached to an N-terminal protein interaction domain. Results from NMR relaxation experiments showed the rotational diffusion for this segment of the intrinsically unstructured linker domain to be correlated with the N-terminal protein interaction domain. When the N-terminal domain is removed, the stable secondary structure is lost and faster rotational diffusion is observed. The large secondary chemical shifts were used to calculate phi and psi dihedral angles and these dihedral angles were used to build a backbone structural model. Restrained molecular dynamics were performed on this new structure using the chemical shift based dihedral angles and a single NOE distance as restraints. In the resulting family of structures a large, solvent exposed loop was observed for the segment of the intrinsically unstructured linker domain that had large secondary chemical shifts.


Asunto(s)
Proteínas de Unión al ADN/química , Conformación Proteica , Replicación del ADN , Proteínas de Unión al ADN/metabolismo , Humanos , Espectroscopía de Resonancia Magnética/métodos , Modelos Moleculares , Estructura Terciaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Proteína de Replicación A
17.
Appl Neuropsychol Child ; 4(3): 166-77, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25117200

RESUMEN

In the search to understand the basis of performance discrepancies, many clinicians are recognizing that, often, factors with no direct relationship to brain functioning influence performance on neuropsychological measures of cognition among children and adolescents. The emergent research on cross-cultural neuropsychology indicates that while the test performance discrepancies do indeed exist, they can be explained by a number of other factors, some of which are known and others that have yet to be operationalized or even identified. While a review of all such factors is beyond the scope of this article, an examination of those that have received the most attention is presented: factors associated with the examinee, factors associated with the neuropsychological measures, cultural competency of the examiner, and factors at the organizational/political level.


Asunto(s)
Atención/fisiología , Cognición/fisiología , Comparación Transcultural , Adolescente , Niño , Competencia Cultural , Humanos , Pruebas Neuropsicológicas
18.
Cancer Nurs ; 38(5): E43-53, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25539166

RESUMEN

BACKGROUND: Given the changes adolescents experience in psychosocial domains as they transition from childhood to young adulthood, the experience of cancer at this time of life is likely to differ in regard to symptom manifestation and relative distress. OBJECTIVE: The purpose of this systematic review is to examine self-reported pain among adolescents diagnosed with leukemia or a brain tumor. METHODS: Electronic searches of MEDLINE, PubMed, and the Cochrane Database of Systematic Reviews since inception to May 2014 were conducted. Search terms included pain; a second term including adolescent, juvenile, youth, child, or childhood; and a third term including cancer, leukemia, or brain tumor. Adolescents were defined as being 10 to 19 years of age. RESULTS: A total of 30 articles met inclusion criteria. Pain was reported associated with the cancer itself, with treatments, and with procedures and was assessed via a variety of measures and methods. Pain was also found to persist long after treatment completion. CONCLUSION: Pain is a frequently reported symptom among adolescents with leukemia or a brain tumor. More consistent inclusion of established measures across studies could increase the availability of data suitable for meta-analyses while also providing information on which aspects of the pain experience are understudied. IMPLICATIONS FOR PRACTICE: Rigorous assessment of pain should be conducted from diagnosis throughout the cancer continuum into long-term survivorship or end of life, with particular attention paid to before and after treatment procedures. Improved pain management incorporating behavioral and/or pharmacological strategies may result in improved quality of life for adolescents with cancer.


Asunto(s)
Neoplasias Encefálicas/complicaciones , Leucemia/complicaciones , Dolor/etiología , Autoinforme , Adolescente , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Humanos , Leucemia/diagnóstico , Leucemia/terapia , Calidad de Vida
19.
Sleep Med ; 15(5): 496-501, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24726572

RESUMEN

UNLABELLED: The purpose of this systematic review was to examine the evidence for sleep-related disturbances among adolescents with cancer, particularly the types of disturbances reported, using single and mixed paediatric oncology samples. METHODS: Electronic searches of Medline, PubMed, and the Cochrane Database of Systematic Reviews since inception to September 2013 were conducted to identify all relevant studies. Search terms included sleep, a second term including adolescent, juvenile, youth, child, or childhood, and a third term including cancer, leukaemia, or brain tumour. A total of 41 articles met inclusion criteria and were included in the review. Of these, 32 included patients with leukaemia and 21 included patients with brain tumours. Sleep-related disturbances included difficulty initiating sleep, fragmented sleep, disordered breathing, parasomnias, napping, daytime sleepiness/fatigue, and unspecified disturbances. Adolescents with cancer experience many problems related to sleep. Given the increase in survival rates of the youth diagnosed with leukaemia or brain tumours, symptom management is an essential area of research in order to continue improving quality of life.


Asunto(s)
Neoplasias/complicaciones , Trastornos del Sueño-Vigilia/etiología , Adolescente , Neoplasias Encefálicas/complicaciones , Trastornos de Somnolencia Excesiva/etiología , Humanos , Leucemia/complicaciones , Parasomnias/etiología , Síndromes de la Apnea del Sueño/etiología
20.
Appl Neuropsychol Child ; 3(1): 66-72, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24236944

RESUMEN

Chronic childhood illnesses have been demonstrated to negatively impact family functioning by introducing new or additive stress on all members of the family system, as well as by increasing financial burden and social isolation. Although these factors have not necessarily been shown to have a direct causal effect on increased rates of abuse in children with chronic illnesses, these children have nonetheless been demonstrated to be at greater risk for neglect and physical and sexual abuse. Children with chronic health care needs are increasingly likely to be referred for neuropsychological evaluation. Thorough assessment of maltreatment would be a valuable addition to all neuropsychological evaluations of children presenting with chronic health conditions.


Asunto(s)
Maltrato a los Niños/diagnóstico , Enfermedad Crónica/psicología , Trastornos Mentales/diagnóstico , Niño , Maltrato a los Niños/psicología , Humanos , Trastornos Mentales/complicaciones , Factores de Riesgo , Encuestas y Cuestionarios
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