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1.
J Sports Sci ; 41(18): 1655-1666, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38126085

RESUMEN

Tracking and measuring elements of performance is a well-established feature of practice in football academies. Player characteristics are considered, tracked, and measured using a variety of methods, with curricula often devised based on perceived importance and data interpretation. Against this breadth, our aim was to investigate the policies and systems in place at category one and two English football academies. Specifically, our objectives were (a) to understand what factors academies believe are important in the development of their players, (b) explore what academies are tracking and how they measure performance, and (c) analyse the extent to which these factors are integrated into the player's curricula. A total of 15 participants with over 10 years' experience across 40 Talent Development (TD) environments were recruited to participate in semi-structured interviews. Using Reflexive Thematic Analysis (RTA), generated themes suggest that academies perceive a differential weighting between performance factors, with greatest importance placed on technical, tactical and psychological factors. A lack of clear measurement systematisation was often apparent. Finally, we identified methods of player curricula integration. We conclude by offering implications for academies to optimise integration of systems and processes that measure and track their players development.


Asunto(s)
Rendimiento Atlético , Fútbol , Humanos , Fútbol/psicología , Aptitud , Curriculum
2.
Pain Manag Nurs ; 23(5): 616-624, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35393218

RESUMEN

BACKGROUND: Pain, drug cravings, and opioid withdrawal symptoms can interfere with substance use disorder or opioid tapering treatment goals. AIM: This pilot study investigated the feasibility of a protocol designed to test opioid withdrawal symptom relief relative to a sham condition after two consecutive days of hyperbaric oxygen therapy (HBOT) for adults prescribed daily methadone for opioid use disorder. METHOD: Using a double-blind protocol, eight adults were randomized to receive either a full 90-minute HBOT dose in a pressurized chamber with 100% oxygen at 2.0 atmospheres absolute (ATA) or a sham condition receiving 21% oxygen (equivalent to room air within the chamber) at a minimal pressure of ≤1.3 ATA. Measures included study retention, treatment satisfaction, and pre- and post-intervention effects for opioid withdrawal symptoms, drug cravings, pain intensity and interference, sleep quality, and mood. RESULTS: Study retention and treatment satisfaction was high. All measurements improved more, on average, for participants receiving full-dose HBOT treatment than among participants receiving sham treatments except for clinically observed withdrawal symptoms. The largest positive effects were observed in measurements of pain intensity and drug craving. CONCLUSIONS: These pilot results provide evidence to support a fully powered study of HBOT as a potential treatment adjunct for adults receiving methadone for opioid use disorder. Trends towards symptom improvements were detected from pre- to post-HBOT in the full treatment arm versus sham condition. More research into novel non-pharmacologic options to relieve distressing symptoms related to pain and opioid use disorder is essential to improve clinical outcomes.


Asunto(s)
Oxigenoterapia Hiperbárica , Trastornos Relacionados con Opioides , Síndrome de Abstinencia a Sustancias , Adulto , Humanos , Analgésicos Opioides/efectos adversos , Oxigenoterapia Hiperbárica/métodos , Metadona , Trastornos Relacionados con Opioides/terapia , Oxígeno , Dolor , Proyectos Piloto , Síndrome de Abstinencia a Sustancias/terapia , Manejo del Dolor
3.
Pain Manag Nurs ; 21(1): 94-99, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31405787

RESUMEN

BACKGROUND: Adults with persistent pain frequently report cannabis use to help manage their symptoms. The impact of cannabis use on cognition in the presence of concurrent symptoms of depression and anxiety is poorly understood. AIMS: Our study explored how cannabis use affects relationships among symptoms of depression, anxiety, and cognition. DESIGN: A cross-sectional survey study was conducted. SETTINGS: Surveys were distributed at outpatient clinics treating adults for pain in the Pacific Northwestern United States. PARTICIPANTS: A total of 150 adults prescribed an opioid medicine for persistent pain were recruited. METHODS: A pencil and paper survey was used to collect several self-reported ratings of cognition, symptoms of depression and anxiety, and the average potency of cannabis consumed as measured by the percentage of delta-9-tetrahydrocannibinol (THC) and cannabidiol (CBD), as well as frequency of cannabis use. RESULTS: Depression, anxiety and cognition significantly worsened as the reported percentage of CBD, THC and overall frequency of cannabis use in the past 30 days increased. Depression and anxiety both significantly predicted worsening cognition in the sample. The relationship between depressive symptoms and cognition was strengthened as reported percentages of CBD use increased. The relationship was the same for anxiety and cognition, although not as strong. CONCLUSIONS: More cannabis use, particularly high CBD products, may be linked with increased symptom burdens and may strengthen relationships between negative affect and cognition. Further cannabis research within persistent pain populations is warranted to add evidence that can assist patients in managing mood and mental processes. Nurses should evaluate how negative affective health symptoms may impact cognition among adults with persistent pain using prescription opioid medications, especially in the context of concurrent cannabis use.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Cognición , Fumar Marihuana/psicología , Adulto , Anciano , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Dolor Crónico/psicología , Estudios Transversales , Depresión/tratamiento farmacológico , Depresión/psicología , Femenino , Humanos , Masculino , Fumar Marihuana/efectos adversos , Persona de Mediana Edad , Psicometría/instrumentación , Psicometría/métodos , Encuestas y Cuestionarios , Washingtón
4.
Behav Pharmacol ; 29(4): 370-374, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29035917

RESUMEN

Despite high rates of smoking (70-90%) and the severely negative impact of smoking on physical and mental health, only 12% of individuals receiving stimulant-use disorder treatment also receive smoking-cessation treatment. The aim of this investigation was to examine the effect of a contingency management (CM) intervention targeting methamphetamine (MA) use on cigarette smoking. Sixty-one adults with MA-use disorders who were smokers were assigned to CM or standard psychosocial treatment. Rates of smoking-negative breath samples (carbon monoxide <3 ppm) were compared between the two groups while controlling for baseline carbon monoxide level, marijuana use, MA use, and time. This subgroup of mostly male (59%) participants included 44 participants in the CM group and 17 participants in the standard psychosocial treatment. Tobacco smoking participants who received CM targeting MA use were 140% (odds ratio: 2.395; 95% confidence interval: 1.073-5.346) more likely to submit a smoking-negative breath sample relative to standard psychosocial treatment during the treatment period, holding constant several other prespecified covariates. This study provides evidence that a behavioral treatment for MA use results in reductions in cigarette smoking in adults with MA-use disorder.


Asunto(s)
Fumar Cigarrillos/psicología , Cese del Hábito de Fumar/métodos , Trastornos Relacionados con Sustancias/psicología , Adulto , Terapia Conductista/métodos , Fumar Cigarrillos/metabolismo , Fumar Cigarrillos/terapia , Femenino , Humanos , Masculino , Metanfetamina/efectos adversos , Persona de Mediana Edad , Datos Preliminares , Fumar/psicología , Trastornos Relacionados con Sustancias/fisiopatología , Fumar Tabaco , Tabaquismo
5.
Am J Drug Alcohol Abuse ; 44(4): 488-496, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29672167

RESUMEN

BACKGROUND: There are sex differences in buprenorphine/naloxone clinical trials for opioid use. While women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment. OBJECTIVES: To test for sex differences in opioid use during a buprenorphine/naloxone clinical trial and determine if sex differences exist in the associations between addiction-related problem areas and opioid use over the course of the trial. METHOD: This secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003 examined sex differences (men = 347, women = 169) in opioid-positive samples in a randomized clinical trial comparing 7-day vs. 28-day buprenorphine/naloxone tapering strategies. Addiction-related problem areas were defined by Addiction Severity-Lite (ASI-L) domain composite scores. RESULTS: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial (B = .33, p = .01) and medical issues were positively related to submitting an opioid-positive sample during treatment for women (B = 1.67, p = .01). No ASI-L domain composite score was associated with opioid-positive samples during treatment for men. CONCLUSION: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial, and medical issues predicted opioid use during treatment for women but not men. Complementary treatment for medical problems during opioid replacement therapy may benefit women.


Asunto(s)
Buprenorfina/uso terapéutico , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Caracteres Sexuales , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos/métodos , Resultado del Tratamiento
6.
Behav Res Methods ; 49(3): 1020-1029, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27325169

RESUMEN

The psychomotor vigilance test (PVT) is widely used to measure reduced alertness due to sleep loss. Here, two newly developed, 3-min versions of the psychomotor vigilance test, one smartphone-based and the other tablet-based, were validated against a conventional 10-min laptop-based PVT. Sixteen healthy participants (ages 22-40; seven males, nine females) completed a laboratory study, which included a practice and a baseline day, a 38-h total sleep deprivation (TSD) period, and a recovery day, during which they performed the three different versions of the PVT every 3 h. For each version of the PVT, the number of lapses, mean response time (RT), and number of false starts showed statistically significant changes across the sleep deprivation and recovery days. The number of lapses on the laptop was significantly correlated with the numbers of lapses on the smartphone and tablet. The mean RTs were generally faster on the smartphone and tablet than on the laptop. All three versions of the PVT exhibited a time-on-task effect in RTs, modulated by time awake and time of day. False starts were relatively rare on all three PVTs. For the number of lapses, the effect sizes across 38 h of TSD were large for the laptop PVT and medium for the smartphone and tablet PVTs. These results indicate that the 3-min smartphone and tablet PVTs are valid instruments for measuring reduced alertness due to sleep deprivation and restored alertness following recovery sleep. The results also indicate that the loss of sensitivity on the 3-min PVTs may be mitigated by modifying the threshold defining lapses.


Asunto(s)
Nivel de Alerta , Atención , Microcomputadores , Privación de Sueño/psicología , Teléfono Inteligente , Adulto , Atención/fisiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Tiempo de Reacción/fisiología , Adulto Joven
7.
J Clin Psychol Med Settings ; 20(3): 275-83, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23615860

RESUMEN

Urinary Incontinence (UI) affects 200 million people worldwide with annual direct costs in the US alone estimated at $16.3 billion. Those with UI have reported a decrease in general quality of life with symptoms of depression, anxiety, low self-esteem, poor body image, and social stigmatization. The purpose of this study was to examine the feasibility of collecting self-reported quality of life data in a self-selected sample of individuals who visited a website providing information, education, and management suggestions regarding UI. Participants included 374 individuals with UI who responded to a solicitation for enrollment in a "Continence Comprehensive Health and Life Assessment" survey posted on The Simon Foundation for Continence website (www.simonfoundation.org). Types of problems and events associated with UI, including social connectivity and quality of life, are discussed along with limitations of the study and implications for future research. Given that 13.01% of respondents had not spoken to a healthcare provider about their UI symptoms, 24.73% had never seen a healthcare professional who "specializes in bladder problems," and 75% said they were not currently using any active approach to managing symptoms, use of such information is discussed in terms of how to construct internet healthcare information to maximize seeking appropriate healthcare services and preparing internet-based information regarding incontinence diagnosis and treatment.


Asunto(s)
Encuestas Epidemiológicas/métodos , Conducta en la Búsqueda de Información/fisiología , Internet , Calidad de Vida/psicología , Autocuidado/psicología , Incontinencia Urinaria/psicología , Actividades Cotidianas/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Conocimientos, Actitudes y Práctica en Salud , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Autocuidado/métodos , Encuestas y Cuestionarios , Estados Unidos , Incontinencia Urinaria/terapia , Adulto Joven
8.
J Addict Nurs ; 34(4): E180-E188, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37772999

RESUMEN

ABSTRACT: Opioids are a leading cause of drug overdose deaths in the United States. Methadone used as medication for opioid use disorder (MOUD) reduces drug cravings and promotes abstinence. However, individuals in methadone-based MOUD treatment commonly report subjective sleep complaints and are at risk for respiratory depression from opioids. We investigated nighttime sleep and respiratory function in eight individuals (six women, two men; ages 31-68 years) in their first 90 days of methadone-based MOUD treatment. Participants underwent overnight cardiorespiratory polysomnography. Sleep and respiratory variables were characterized with descriptive statistics for comparison to reference data from similarly aged healthy adults. Although participants spent 8.1 ± 0.3 hours (mean ± SD ) in bed, their total sleep time was only 6.8 ± 1.3 hours. They exhibited longer sleep latency and intermittent wakefulness. Sleep structure was irregular, with disrupted sleep cycles. Participants also displayed a decreased amount of N1 sleep and an increased amount of N3 sleep, compared with reference data. Participants showed respiratory depression, with an average apnea-hypopnea index of 16.5 ± 8.9 events per hour. Central sleep apneas comprised 69.1% ± 20.9% of the respiratory events. A Cheyne-Stokes-like breathing pattern, consisting of 30-second cycles of three central sleep apneas, was observed in 75% of participants. Our results suggest that individuals early in methadone-based MOUD treatment experience disordered sleep and respiratory disturbances. Such nighttime physiological changes may have serious long-term health consequences and contribute to unintended overdose rates. Identifying and treating MOUD individuals with sleep apnea could reduce risk of death.


Asunto(s)
Trastornos Relacionados con Opioides , Insuficiencia Respiratoria , Apnea Central del Sueño , Adulto , Masculino , Humanos , Femenino , Estados Unidos , Anciano , Metadona/uso terapéutico , Apnea Central del Sueño/tratamiento farmacológico , Sueño , Trastornos Relacionados con Opioides/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Insuficiencia Respiratoria/tratamiento farmacológico
9.
Clin Pharmacol Ther ; 113(6): 1315-1325, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36924284

RESUMEN

Oral formulations prepared from the leaves of the kratom (Mitragyna speciosa) plant are increasingly used for their opioid-like effects to self-manage opioid withdrawal and pain. Calls to US poison centers involving kratom exposures increased >50-fold from 2011-2017, one-third of which reported concomitant use of kratom with drugs of abuse. Many of these drugs are eliminated primarily via cytochrome P450 (CYP) 3A and CYP2D6, raising concerns for potential adverse pharmacokinetic kratom-drug interactions. The impact of a single low dose of kratom tea (2 g) on the pharmacokinetics of the CYP3A probe midazolam (2.5 mg) and CYP2D6 probe dextromethorphan (30 mg) were assessed in 12 healthy adult participants after oral administration. Kratom showed no effect on dextromethorphan area under the plasma concentration time-curve (AUC) and maximum concentration (Cmax ; geometric mean ratio (90% confidence interval) 0.99 (0.83-1.19) and 0.96 (0.78-1.19), respectively) but a modest increase in midazolam AUC and Cmax (1.39 (1.23-1.57) and 1.50 (1.32-1.70), respectively). Lack of change in midazolam half-life (1.07 (0.98-1.17)) suggested that kratom primarily inhibited intestinal CYP3A. This inference was further supported by a physiologically based pharmacokinetic drug interaction model using the abundant alkaloid mitragynine, a relatively potent CYP3A time-dependent inhibitor in vitro (KI , ~4 µM; kinact , ~0.07 min-1 ). This work is the first to clinically evaluate the pharmacokinetic drug interaction potential of kratom. Co-consuming kratom with certain drugs extensively metabolized by CYP3A may precipitate serious interactions. These data fill critical knowledge gaps about the safe use of this increasingly popular natural product, thereby addressing ongoing public health concerns.


Asunto(s)
Productos Biológicos , Mitragyna , Adulto , Humanos , Analgésicos Opioides/efectos adversos , Midazolam/efectos adversos , Citocromo P-450 CYP2D6 , Citocromo P-450 CYP3A , Dextrometorfano , Psicotrópicos/efectos adversos , Interacciones Farmacológicas , Inhibidores del Citocromo P-450 CYP3A
10.
Clin Transl Sci ; 16(10): 1779-1790, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37639334

RESUMEN

Green tea is a popular beverage worldwide. The abundant green tea catechin (-)-epigallocatechin gallate (EGCG) is a potent in vitro inhibitor of intestinal UDP-glucuronosyltransferase (UGT) activity (Ki ~2 µM). Co-consuming green tea with intestinal UGT drug substrates, including raloxifene, could increase systemic drug exposure. The effects of a well-characterized green tea on the pharmacokinetics of raloxifene, raloxifene 4'-glucuronide, and raloxifene 6-glucuronide were evaluated in 16 healthy adults via a three-arm crossover, fixed-sequence study. Raloxifene (60 mg) was administered orally with water (baseline), with green tea for 1 day (acute), and on the fifth day after daily green tea administration for 4 days (chronic). Unexpectedly, green tea decreased the geometric mean green tea/baseline raloxifene AUC0-96h ratio to ~0.60 after both acute and chronic administration, which is below the predefined no-effect range (0.75-1.33). Lack of change in terminal half-life and glucuronide-to-raloxifene ratios indicated the predominant mechanism was not inhibition of intestinal UGT. One potential mechanism includes inhibition of intestinal transport. Using established transfected cell systems, a green tea extract normalized to EGCG inhibited 10 of 16 transporters tested (IC50 , 0.37-12 µM). Another potential mechanism, interruption by green tea of gut microbe-mediated raloxifene reabsorption, prompted a follow-up exploratory clinical study to evaluate the potential for a green tea-gut microbiota-drug interaction. No clear mechanisms were identified. Overall, results highlight that improvements in current models and methods used to predict UGT-mediated drug interactions are needed. Informing patients about the risk of co-consuming green tea with raloxifene may be considered.


Asunto(s)
Catequina , , Adulto , Humanos , Catequina/farmacología , Interacciones Farmacológicas , Glucurónidos , Clorhidrato de Raloxifeno/farmacología , Té/química , Estudios Cruzados
11.
J Addict Nurs ; 33(1): 27-36, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35230058

RESUMEN

ABSTRACT: Opioid withdrawal symptoms can interfere with substance use disorder treatment goals. This study investigated the acceptability, feasibility, and treatment effects of hyperbaric oxygen therapy (HBOT) as an adjunct to reduce withdrawal symptoms for adults initiating a medically supervised methadone dose reduction. Adults prescribed methadone for opioid use disorder were randomized into either a hyperbaric oxygen group (n = 17) or an attention control group (n = 14). The study site was an outpatient opioid treatment program in the northwestern United States. Participants were asked to attend five consecutive daily 90-minute HBOT sessions offered at 2.0 atmospheres absolute with 100% oxygen in a pressurized chamber. Treatment attendance and reported satisfaction were measures of acceptability and feasibility. Medication doses were tracked posttreatment at 1 week, 1 month, and 3 months. Withdrawal symptoms were assessed at baseline and daily during the 5-day intervention period. After randomization, 13 (76.5%) followed through with medical screening and HBOT sessions, and of those, nine (69.2%) completed all five 90-minute HBOT sessions. At 3 months, the treatment group maintained, on average, a 4.3-mg methadone dose reduction compared with an average reduction of 0.25 mg for control group participants. Opioid withdrawal symptoms were reduced after Day 1 of HBOT by twice as much, on average, compared with the control condition. Satisfaction surveys found participants were generally satisfied with ease and comfort of the treatment. The evidence that HBOT is an acceptable, feasible adjunct warrants future trials to determine more conclusively effects on withdrawal symptoms associated with methadone dose taper.


Asunto(s)
Oxigenoterapia Hiperbárica , Trastornos Relacionados con Opioides , Adulto , Humanos , Metadona/uso terapéutico , Narcóticos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Oxígeno/uso terapéutico
12.
Pharmaceutics ; 14(3)2022 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-35335999

RESUMEN

Increasing use of the botanical kratom to self-manage opioid withdrawal and pain has led to increased kratom-linked overdose deaths. Despite these serious safety concerns, rigorous fundamental pharmacokinetic knowledge of kratom in humans remains lacking. We assessed the pharmacokinetics of a single low dose (2 g) of a well-characterized kratom product administered orally to six healthy participants. Median concentration-time profiles for the kratom alkaloids examined were best described by a two-compartment model with central elimination. Pronounced pharmacokinetic differences between alkaloids with the 3S configuration (mitragynine, speciogynine, paynantheine) and alkaloids with the 3R configuration (mitraciliatine, speciociliatine, isopaynantheine) were attributed to differences in apparent intercompartmental distribution clearance, volumes of distribution, and clearance. Based on noncompartmental analysis of individual concentration-time profiles, the 3S alkaloids exhibited a shorter median time to maximum concentration (1-2 vs. 2.5-4.5 h), lower area under the plasma concentration-time curve (430-490 vs. 794-5120 nM × h), longer terminal half-life (24-45 vs. ~12-18 h), and higher apparent volume of distribution during the terminal phase (960-12,700 vs. ~46-130 L) compared to the 3R alkaloids. Follow-up mechanistic in vitro studies suggested differential hepatic/intestinal metabolism, plasma protein binding, blood-to-plasma partitioning, and/or distribution coefficients may explain the pharmacokinetic differences between the two alkaloid types. This first comprehensive pharmacokinetic characterization of kratom alkaloids in humans provides the foundation for further research to establish safety and effectiveness of this emerging botanical product.

14.
Mil Med ; 186(Suppl 1): 246-252, 2021 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-33499519

RESUMEN

INTRODUCTION: Military operations often involve intense exposure to stressors combined with acute sleep deprivation, while military personnel also experience high prevalence of chronic sleep deficiency from insomnia and other sleep disorders. However, the impact of acute and chronic sleep deficiency on physiologic stressor responses is poorly understood. In a controlled laboratory study with normal sleepers and individuals with chronic sleep-onset insomnia, we measured responses to an acute stressor administered in a sleep deprivation condition or a control condition. METHODS: Twenty-two adults (aged 22-40 years; 16 females)-11 healthy normal sleepers and 11 individuals with sleep-onset insomnia-completed a 5-day (4-night) in-laboratory study. After an adaptation day and a baseline day, subjects were assigned to a 38-hour total sleep deprivation (TSD) condition or a control condition; the study ended with a recovery day. At 8:00 PM after 36 hours awake in the sleep deprivation condition or 12 hours awake in the control condition, subjects underwent a Maastricht Acute Stress Test (MAST). Salivary cortisol was measured immediately before the MAST at 8:00 PM, every 15 minutes after the MAST from 8:15 PM until 9:15 PM, and 30 minutes later at 9:45 PM. Baseline salivary cortisol was collected in the evening of the baseline day. Additionally, before and immediately upon completion of the MAST, self-report ratings of affect and pain were collected. RESULTS: The MAST elicited a stressor response in both normal sleepers and individuals with sleep-onset insomnia, regardless of the condition, as evidenced by increases in negative affect and pain ratings. Relative to baseline, cortisol levels increased immediately following the MAST, peaked 30 minutes later, and then gradually returned to pre-MAST levels. At the cortisol peak, there was a significant difference across groups and conditions, reflecting a pronounced blunting of the cortisol response in the normal sleepers in the TSD condition and the sleep-onset insomnia group in both the TSD and control conditions. CONCLUSIONS: Blunted stressor reactivity as a result of sleep deficiency, whether acute or chronic, may reflect reduced resiliency attributable to allostatic load and may put warfighters at increased risk in high-stakes, rapid response scenarios.


Asunto(s)
Privación de Sueño , Trastornos del Inicio y del Mantenimiento del Sueño , Adaptación Fisiológica , Adulto , Femenino , Humanos , Hidrocortisona , Masculino , Sueño , Privación de Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Adulto Joven
15.
Clin Pharmacol Ther ; 109(5): 1342-1352, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33174626

RESUMEN

The botanical natural product goldenseal can precipitate clinical drug interactions by inhibiting cytochrome P450 (CYP) 3A and CYP2D6. Besides P-glycoprotein, effects of goldenseal on other clinically relevant transporters remain unknown. Established transporter-expressing cell systems were used to determine the inhibitory effects of a goldenseal extract, standardized to the major alkaloid berberine, on transporter activity. Using recommended basic models, the extract was predicted to inhibit the efflux transporter BCRP and uptake transporters OATP1B1/3. Using a cocktail approach, effects of the goldenseal product on BCRP, OATP1B1/3, OATs, OCTs, MATEs, and CYP3A were next evaluated in 16 healthy volunteers. As expected, goldenseal increased the area under the plasma concentration-time curve (AUC0-inf ) of midazolam (CYP3A; positive control), with a geometric mean ratio (GMR) (90% confidence interval (CI)) of 1.43 (1.35-1.53). However, goldenseal had no effects on the pharmacokinetics of rosuvastatin (BCRP and OATP1B1/3) and furosemide (OAT1/3); decreased metformin (OCT1/2, MATE1/2-K) AUC0-inf (GMR, 0.77 (0.71-0.83)); and had no effect on metformin half-life and renal clearance. Results indicated that goldenseal altered intestinal permeability, transport, and/or other processes involved in metformin absorption, which may have unfavorable effects on glucose control. Inconsistencies between model predictions and pharmacokinetic outcomes prompt further refinement of current basic models to include differential transporter expression in relevant organs and intestinal degradation/metabolism of the precipitant(s). Such refinement should improve in vitro-in vivo prediction accuracy, contributing to a standard approach for studying transporter-mediated natural product-drug interactions.


Asunto(s)
Productos Biológicos/farmacocinética , Evaluación de Medicamentos/métodos , Interacciones de Hierba-Droga , Hydrastis , Adulto , Alcaloides/farmacocinética , Productos Biológicos/química , Estudios Cruzados , Femenino , Furosemida/farmacocinética , Células HEK293 , Humanos , Hydrastis/química , Masculino , Metformina/farmacocinética , Midazolam/farmacocinética , Transportadores de Anión Orgánico/antagonistas & inhibidores , Transportadores de Anión Orgánico/metabolismo , Proteínas de Transporte de Catión Orgánico/antagonistas & inhibidores , Proteínas de Transporte de Catión Orgánico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Rosuvastatina Cálcica/farmacocinética
16.
Chronobiol Int ; 37(9-10): 1457-1460, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32815424

RESUMEN

Total sleep deprivation (TSD) and time-on-task (TOT), especially in combination, increase cognitive instability and cause performance impairment. There are large inter-individual differences in TSD and TOT effects which, in part, have a genetic basis. Here, we show that the dopamine receptor D2 C957T genetic polymorphism predicts the magnitude of the TOT effect on a psychomotor vigilance test (PVT) during 38 h of TSD. This finding indicates that dopamine availability in the striatum, where the dopamine receptor D2 is most prevalent, influences the TOT effect, suggesting a role for dopaminergic pathways in sustained attention deficits during sleep loss.


Asunto(s)
Ritmo Circadiano , Privación de Sueño , Genotipo , Humanos , Desempeño Psicomotor , Tiempo de Reacción , Receptores de Dopamina D2/genética , Privación de Sueño/genética , Vigilia
17.
Chronobiol Int ; 37(9-10): 1441-1444, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32842800

RESUMEN

Total sleep deprivation (TSD) is known to impair sustained attention. However, previously reported effects of TSD on response inhibition are mixed. We administered a "stop-signal" variation of the psychomotor vigilance test, which included 25% of trials requiring withholding of a response to assess response inhibition alongside sustained attention. Participants completed the task at baseline and after 34.5 h of wakefulness. Accuracy was not reduced during TSD. However, response times were significantly slower. A speed/accuracy trade-off allowed participants to effectively withhold responses on inhibition trials and conferred resilience of inhibitory control during TSD under conditions of relatively low time pressure.


Asunto(s)
Desempeño Psicomotor , Privación de Sueño , Atención , Ritmo Circadiano , Humanos , Tiempo de Reacción , Sueño , Vigilia
18.
Chronobiol Int ; 37(9-10): 1465-1468, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32954864

RESUMEN

There are large inter-individual differences in slow wave sleep, which constitute a trait or phenotype. We investigated whether the manifestation of this trait is impacted by daytime sleeping after sleep deprivation, and to what extent it is robust to prior caffeine intake. N = 12 subjects underwent three 48 h periods of total sleep deprivation with different caffeine dosing regimens. There were significant, considerable, and robust inter-individual differences in slow wave sleep across nighttime sleep opportunities before, and daytime sleep after, total sleep deprivation, regardless of caffeine dosing. The robustness of this phenotype may have functional implications for individuals in around-the-clock operational settings.


Asunto(s)
Cafeína , Sueño de Onda Lenta , Ritmo Circadiano , Humanos , Individualidad , Sueño , Privación de Sueño , Vigilia
20.
Nat Sci Sleep ; 11: 401-410, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31849552

RESUMEN

PURPOSE: Individuals with primary insomnia frequently report cognitive impairment as a next-day consequence of disrupted sleep. Studies attempting to quantify daytime impairment objectively in individuals with insomnia have yielded mixed results, with evidence suggesting impairments in aspects of executive functioning but not psychomotor vigilance. It has been suggested that persons with insomnia may have latent performance deficits for which they would be able to compensate effectively under normal daytime circumstances - suggesting that any such deficits may be exposed through perturbation. In this context, we used a laboratory-based total sleep deprivation (TSD) paradigm to investigate psychomotor vigilance performance in individuals with chronic sleep-onset insomnia as compared to healthy normal controls. PARTICIPANTS AND METHODS: Fourteen participants, seven individuals with chronic sleep-onset insomnia (ages 24-40y) and seven age-matched, healthy normal sleepers completed a highly controlled in-laboratory study involving 38 h of TSD. A 10 min and a 3 min version of the psychomotor vigilance test (PVT) were administered every 3 h during TSD. RESULTS: In both the individuals with sleep-onset insomnia and the age-matched normal sleepers, lapses of attention and false starts on the PVT were relatively infrequent during the first 16 h of the TSD period, but increased significantly when wakefulness was extended beyond 16 h. However, the effects of TSD on PVT performance were considerably exacerbated in the sleep-onset insomnia group, which showed about twice as many lapses of attention, more than twice as many false starts, and approximately twice as big a time-on-task effect on the 10 min PVT as the age-matched normal sleepers group, with similar findings on the 3 min PVT. CONCLUSION: These findings indicate that daytime impairment reported by individuals with sleep-onset insomnia has an objective performance component that is exposed during TSD. Thus, persons with sleep-onset insomnia could be at increased risk of performance impairment in settings that involve extended wakefulness. This underscores the importance of treating insomnia and suggests that laboratory sleep deprivation studies could serve to document the effectiveness of treatment approaches.

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