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BACKGROUND: Sleep, physical activity (PA) and sedentary behavior (SED) have bidirectional associations with mental health in children. The relationships among sleep, PA, SED, with depressive and fatigue symptoms have not been investigated in Pediatric Onset Multiple Sclerosis (POMS) but are needed to inform sleep and PA behavior change interventions. OBJECTIVES: (1) To describe sleep quality including: sleep efficiency, latency, total sleep time, number of awakenings, time in bed, and wake after sleep onset using actigraphy in children and adolescents ages 11 to 18 diagnosed with POMS, and to compare these sleep metrics to those of an age- and sex-matched non-MS group (2) To examine the relationship between time spent in sedentary, light (LIPA), moderate and vigorous PA (MVPA), sleep quality, with depression, fatigue, and quality of life in children and adolescents with POMS and an age and sex matched non-MS group. METHODS: A cross-sectional study recruited children and adolescents with POMS ages 11 to 18 years followed at a tertiary pediatric hospital (Toronto, Canada) and an age and sex matched non-MS group from the general population. Participants were consented prior to initiation of study procedures. Participants wore an Actiwatch monitor and GT3X accelerometer and completed standardized questionnaires validated to capture data on sleep disturbances, depression, fatigue, and quality of life. Objective sleep data were collected using an Actiwatch including sleep efficiency, total sleep time, number of awakenings, wake after sleep onset (WASO), and sleep latency. A GT3X accelerometer was used to collect PA data including time spent in SED, light (LPA), and moderate to vigorous (MVPA) PA. Correlational analyses and tests of difference were used to compare the groups. RESULTS: 25 POMS (21F; 16.6 years ±1.1 yrs., median Expanded Disability Status Scale (EDSS) =1.5, IQR=1) and 25 Non-MS (22 F; 16±1.3 yrs.) took part. POMS had higher BMI (T= -5.1, P<0.001) compared to Non-MS. No differences in sleep efficiency (MS mean = 87%, vs. 88%) sleep time (MS Mean = 7.3 hrs. vs. 7.4 hrs.,), WASO (MS mean=37 mins. vs. 36 mins), latency (MS mean=15 mins vs. 11 mins), SED (MS mean =763 mins. vs. 730 mins) or PA (MS, mean LPA = 68 mins. vs 60 mins; MS mean MVPA = 12.7 mins. vs. 12.4 mins). Within POMS, higher sleep efficiency was associated with more SED (SR= 0.4, p = 0.05), while higher sleep efficiency was associated with less SED in Non-MS (SR = -0.7, p< 0.0). In children with POMS, less sleep time, shorter sleep onset latency and more WASO was associated with more SED (SR range = -0.45 to -0.58, P< 0.01). Higher sleep efficiency was associated with less fatigue. Less WASO was associated with lower depression, lower fatigue (SR = 0.67, p<0.01) and better quality of life (SR= -0.6, p<0.01). Greater LPA was associated with lower sleep onset latency (-0.45, p<0.05). CONCLUSIONS: Children with POMS did not differ in Actiwatch monitored sleep quality metrics. However, within the POMS group sleep quality was associated with better fatigue, depression and QOL. Further, total sleep time, WASO and latency associated with time spent SED and LPA, which independently associate with mental health outcome. Longitudinal work should determine the temporal associations between WASO, sleep latency, sleep time, PA, and mental health outcomes and whether reallocation of specific sleep or PA behaviors (time to sleep, total sleep time, sedentary to MVPA) result in improved depression fatigue, or quality of life in children and adolescents with POMS.
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Esclerosis Múltiple , Calidad de Vida , Humanos , Niño , Adolescente , Estudios Transversales , Esclerosis Múltiple/epidemiología , Ejercicio Físico , Sueño , Fatiga/epidemiología , Fatiga/etiología , Acelerometría/métodosRESUMEN
Background: The use of 3D imaging is becoming increasingly common, so too is the use of fiducial markers to identify/track regions of interest and assess material deformation. While many different materials have been used as fiducials, they are often used in isolation, with little comparison to one another. Objective: In the current study, we aim to directly compare different Computed Tomography (CT and µCT) fiducial materials, both metallic and nonmetallic. Methods: µCT imaging was performed on a soft-tissue structure, in this case heart valve tissue, with various markers attached. Additionally, we evaluated the same markers with DiceCT stained tissue in a fluid medium. Eight marker materials were tested in all. Results: All of the metallic markers generated significant artifacts and were found unsuitable for soft-tissue µCT imaging, whereas alumina markers were found to perform the best, with excellent contrast and consistency. Conclusions: These findings support the further use of alumina as fiducial markers for soft material and tissue studies that utilize CT and µCT imaging.
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BACKGROUND: Higher levels of moderate to vigorous physical activity (MVPA) associate with disease activity in pediatric multiple sclerosis (MS). Further, measures of retinal integrity associate with lower brain atrophy, yet the relationship of retinal integrity with MVPA has not been investigated. OBJECTIVE: To determine the relationship between MVPA and retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness in patients with MS, myelin oligodendrocyte glycoprotein-associated disorders (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), and monophasic acquired demyelinating syndromes (monoADS). METHODS: 150 consecutive children ≤18 y.o with neuroinflammatory disorders were included. Outcomes included the Godin Leisure Time Activity Questionnaire (GLTEQ) modeled as both a continuous and categorical variable (any vs no MVPA/Strenuous activity), and RNFL and GCIPL using linear mixed models (JASP 0.14.1). RESULTS: An association was identified between MVPA with RNFL thickness (F (1,133) = 8.40, p = .004) and GCIPL thickness (F(1, 131) = 7.68, p = .006). In the MS cohort, any strenuous physical activity was associated with greater RNFL (F(1,35) = 7.30, p = .011) and GCIPL thickness (F(1,35) = 8.73, p =.006). CONCLUSIONS: Any MVPA participation is associated with higher RNFL and GCIPL thickness across neuroinflammatory disorders.
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Esclerosis Múltiple , Células Ganglionares de la Retina , Adolescente , Benchmarking , Niño , Ejercicio Físico , Humanos , Enfermedades Neuroinflamatorias , Tomografía de Coherencia ÓpticaRESUMEN
BACKGROUND: Youth with multiple sclerosis (MS) have high levels of disease activity, depression and fatigue, and lower moderate to vigorous physical activity (PA). PA participation is associated with lower disease activity, depression and fatigue as well as higher self-efficacy, goal setting and decreased barriers. These latter constructs may be targeted by an intervention program for behavior change, and such intervention must account for disease rarity, geographical proximity and time constraints which limit the feasibility, accessibility, and sustainability of implementing a PA intervention in youth with MS. We have developed a theory-informed mobile-app based PA promotion program to address these barriers, Active Teens with Multiple Sclerosis (ATOMIC) and herein report the feasibility of delivering this intervention in youth with MS. OBJECTIVE: To determine the feasibility of delivering the ATOMIC program to youth with MS. METHODS: Fifteen youth with MS (13F, 16.6⯱â¯1.2 years) followed at the Hospital for Sick Children were enrolled in the ATOMIC intervention. Participants underwent a standard clinical evaluation; an exercise test to determine cardiorespiratory fitness; 7-day PA monitoring with an accelerometer; and completed standardized depression, fatigue questionnaires at baseline and post-intervention. Social cognitive scales related to self-efficacy, self-management, goal setting, perceived barriers, outcome expectancy, and social support were completed at baseline, six and 12-weeks. The 12-week mobile app PA intervention was informed by Social Cognitive Theory (SCT) and included: individualized PA coaching, PA self-monitoring (Fitbit), goal setting, social support and MS specific educational modules. Feasibility was defined as (1) meeting the recruitment target of 15 participants within a one-year period; (2) completion of ≥80% of study related questionnaires and testing; (3) a drop-out rate of less than 20%, and (4) adherence to the ATOMIC intervention program components of ≥80% (Fitbit wear, PA coaching calls, modules). RESULTS: From March 2018 to April 2019, 53% of youth approached agreed to participate (15/28). 13/15 participants completed the intervention. 36 of the possible 39 coaching calls (92%: 3 possible phone calls per participant); 89% wear adherence to FitbitCharge2 data (meanâ¯=â¯75⯱â¯16.6 days of 84 days); and 5/12 (42%) of modules were completed. An average 8.4% (SD= 40%, rangeâ¯=â¯-74.0 to 176%) increase in Fitbit steps above the first week of the intervention were observed. PA level from accelerometry at 12-weeks, aerobic fitness, depression and fatigue were unchanged. SCT scales indicated an increase in social support from friends (0.67-points, Tâ¯=â¯2.7, pholm=0.04), and a decrease in outcome expectancy (-2.7, Tâ¯=â¯3.0, pholm=0.03). There were no differences in self-efficacy, self-management or perceived barriers post intervention. CONCLUSIONS: Our results indicate that the ATOMIC program is feasible for delivery in youth with MS. Future work is needed to understand how to best implement each element of SCT through added features in the mobile-app, and to evaluate how the individual components of SCT mediate change in PA behaviours of youth with MS.
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Aplicaciones Móviles , Esclerosis Múltiple , Adolescente , Niño , Ejercicio Físico , Fatiga/complicaciones , Estudios de Factibilidad , Humanos , Esclerosis Múltiple/complicacionesRESUMEN
Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.
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Incendios , Incendios Forestales , Ecosistema , Bosques , Humanos , América del NorteRESUMEN
BACKGROUND: Heart valve computational models require high quality geometric input data, commonly obtained using micro-computed tomography. Whether in the open or closed configuration, most studies utilize dry valves, which poses significant challenges including gravitational and surface tension effects along with desiccation induced mechanical changes. OBJECTIVE: These challenges are overcome by scanning in a stress-free configuration in fluid. Utilizing fluid backgrounds however reduces overall contrast due to the similar density of fluid and tissue. METHODS: The work presented here demonstrates imaging of the mitral valve by utilizing an iodine-based staining solution to improve the contrast of valve tissue against a fluid background and investigates the role of stain time and concentration. RESULTS: It is determined that an Olea europaea oil bath with a relatively high concentration, short stain time approach produces high quality imagery suitable for creating accurate 3D renderings. CONCLUSIONS: Micro-CT scanning of heart valves in fluid is shown to be feasible using iodine staining techniques.
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We tested 3-methyl-2-cyclohexen-1-one (MCH) and novel semiochemicals as potential spruce beetle (Dendroctonus rufipennis Kirby) (Coleoptera: Curculionidae, Scolytinae) repellents over multiple years in Utah and Colorado trapping bioassays. MCH is a known spruce beetle repellent and our testing revealed Acer kairomone blend (AKB) and isophorone plus sulcatone as repellents. We subsequently tested these semiochemicals for area and single tree protection to prevent spruce beetle attacks at locations in Utah, Colorado, Wyoming, New Mexico, and Alaska. Individual tree protection trials found MCH-AKB provided significant protection against spruce beetle attacks in the southern Rocky Mountains but not in Alaska. Adding sulcatone or doubling MCH-AKB pouches did not further enhance protection. A degree of protection was extended to spruce at least 10 m distant from the repellents, including in Alaska. Tree diameter was not a significant covariate among treated trees but was positively correlated with the probability of infestation for surrounding spruce. In area protection trials, spruce in control plots were 2.4 times more likely to be in a higher severity attack class compared with spruce in plots treated with MCH-AKB pouches deployed at 30 sets per hectare. Tree diameter had a significant, positive relationship to the probability of infestation. We found MCH-AKB to offer a high degree of protection against beetle attack in Engelmann spruce (Picea engelmannii Parry ex Engelm.) (Pinales: Pinaceae) (Picea engelmannii Parry ex Engelm.) (Pinales: Pinaceae), especially for single tree protection (66% of control trees were strip- or mass-attacked compared with 6% of repellent-treated trees). AKB requires registration and labeling, however, before this economical and environmentally benign semiochemical can be used operationally.
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Escarabajos , Picea , Gorgojos , Animales , Colorado , New Mexico , Feromonas , UtahRESUMEN
BACKGROUND: Venlafaxine is a serotonin noradrenaline reuptake inhibitor used to treat major depressive episodes and anxiety disorders. The primary aim of this study was to investigate spontaneous abortion risks following gestational exposure. METHODS: This prospective observational comparative cohort study utilised data collected by the UK Teratology Information Service (UKTIS) between 1995 and 2018. The study sample included 281 venlafaxine exposed pregnancies matched to antidepressant unexposed (n = 1405) and SSRI exposed (n = 843) comparator groups. RESULTS: After correction for variation in competing outcome rates and the stage of pregnancy at reporting, no statistically significant differences in the hazard of spontaneous abortion was observed following gestational venlafaxine use compared with either antidepressant unexposed (HR 1.28, 95% CI; 0.850-1.94) or SSRI exposed (HR 1.03, 95% CI; 0.681-1.57) pregnancies. CONCLUSIONS: No conclusive evidence is provided from this study that venlafaxine increases the risk of adverse pregnancy or fetal outcomes.
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Antidepresivos/uso terapéutico , Resultado del Embarazo/epidemiología , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéutico , Clorhidrato de Venlafaxina/uso terapéutico , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , Estudios Prospectivos , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: To estimate the total costs of treating head and neck cancers, specifically oropharyngeal, laryngeal and oral cavity cancer, in secondary care facilities in England during the period 2006/2007 to 2010/2011. DESIGN: Patient records were extracted from an English hospital database to estimate the number of patients treated for oropharyngeal, laryngeal and oral cavity cancer in England. Identified resource use was linked to published United Kingdom cost estimates to quantify the reimbursement of treatment through the Payment by Results system. SETTING: Retrospective hospital data analysis. PARTICIPANTS: From the hospital data, patient records of patients treated for oropharyngeal, laryngeal and oral cavity cancer were selected. MAIN OUTCOME MEASURES: Annual total costs of treatment, stratified by inpatient and outpatient setting and by male and female patients. RESULTS: From 2006/2007 to 2010/2011, total costs of treatment across the three head and neck cancer sites were estimated to be approximately £309 million, with 90% attributable to inpatient care (bundled costs). Oropharyngeal cancer accounted for 37% of total costs. Costs and patient numbers increased over time, largely due to a rise in oropharyngeal cancer, where total costs increased from £17.21 million to £30.32 million, with over 1400 (52%) more inpatients treated in 2010/11 compared to 2006/07. CONCLUSIONS: In 4 years, the number of patients with oropharyngeal cancer receiving some form of inpatient care increased by more than half, and associated costs increased by three quarters. This reinforces the case for prevention and early detection strategies to help contain this epidemiological and economic burden.
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Costo de Enfermedad , Gastos en Salud/tendencias , Neoplasias Orofaríngeas/economía , Terapia Combinada/economía , Bases de Datos Factuales , Inglaterra , Humanos , Neoplasias Orofaríngeas/terapia , Estudios RetrospectivosRESUMEN
Varenicline is a smoking cessation aid for which limited data exist concerning safety during human pregnancy. This multicentre prospective observational comparative cohort study was undertaken using surveillance data collected by the European Network of Teratology Information Services. The study sample consisted of 89 varenicline exposed pregnancies and two matched comparator groups; 267 non-teratogen exposed (NTE) controls and 78 exposed to nicotine replacement therapy or bupropion (NRT/B) for smoking cessation. For all exposed pregnancies, varenicline use only occurred in the first trimester, with a considerable proportion discontinuing use in the very early stages of pregnancy. The major congenital malformation rate (n=2/89, 2.25%) was in keeping with the expected background rate (2-4%), and was not significantly increased for first trimester varenicline-exposed infants in comparison with non-exposed controls (vs. NTE: OR 2.02, 95%CI 0.166 to 17.9, vs. NRT/B: OR 0.874, 95%CI 0.0620 to 12.3). However, the small sample size produced very imprecise risk estimates.
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Anomalías Congénitas/epidemiología , Exposición Materna/efectos adversos , Agonistas Nicotínicos/toxicidad , Resultado del Embarazo/epidemiología , Dispositivos para Dejar de Fumar Tabaco/efectos adversos , Vareniclina/toxicidad , Anomalías Congénitas/etiología , Monitoreo Epidemiológico , Europa (Continente) , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Estudios ProspectivosRESUMEN
INTRODUCTION: Haemophilia is a bleeding disorder characterized by musculoskeletal bleeding. Trauma-induced bleeding into joints and muscles may be associated with participation in physical activities. Recognizing this, persons with haemophilia may limit physical activities to avoid bleeding. The characterization of physical activity profiles (type, intensity, frequency and duration) in children with differing severities of haemophilia has not been well documented. This is required to better understand the relationship between physical activity and bleeding in children with haemophilia. AIM: This study was a prospective, cross-sectional, observational study to compare the quantity, type and intensity of physical activity as measured by accelerometry in boys with different haemophilia severities. METHODS: Subjects wore an accelerometer daily for 1 week and completed validated self-report PedHAL and 3DPAR questionnaires. Accelerometer activity levels were classified as sedentary, light, moderate or vigorous. RESULTS: A total of 66 males were enrolled, 24 had mild/moderate and 42 had severe haemophilia. Subjects average age was 11.52 years (±3.99) and their average BMI was 20.74 kg m(2) (±5.68). Boys with severe haemophilia reported significantly more time per day spent in sedentary activities compared to those with mild/moderate haemophilia. Furthermore, the amount of time engaged in sedentary activities increased with age in those boys with severe haemophilia, whereas the opposite was true in those with mild/moderate haemophilia. CONCLUSION: We speculate that prophylaxis in children with severe haemophilia permitted them to engage in similar amounts of moderate to vigorous physical activity (MVPA) as children with mild/moderate haemophilia. Increasing sedentary time in the severe cohort with age may be attributed to increasing arthropathy among other psychosocial factors.
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Ejercicio Físico , Hemofilia A/epidemiología , Actividad Motora , Acelerometría , Adolescente , Niño , Estudios Transversales , Progresión de la Enfermedad , Hemofilia A/fisiopatología , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Autoinforme , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To conduct enhanced surveillance for signals of teratogenesis following use of the neuraminidase inhibitors zanamivir and oseltamivir in the treatment or post-exposure prophylaxis of 2009 A/H1N1 influenza during pregnancy. DESIGN: Prospective cohort study, using national surveillance data collected by the UK Teratology Information Service (UKTIS) during the 2009 A/H1N1 pandemic. SETTING: United Kingdom. POPULATION: Pregnant women who were reported to UKTIS by healthcare professionals seeking advice about exposure to zanamivir and oseltamivir or to other non-teratogenic drugs. METHODS: Pregnancy outcomes were collected for prospectively reported pregnancies exposed to zanamivir (n = 180) or oseltamivir (n = 27), and compared with a reference group of 575 prospectively reported pregnancies exposed to non-teratogenic drugs over the same period. MAIN OUTCOME MEASURES: Rates of major congenital malformation, preterm delivery and low birth weight. RESULTS: No significant differences in overall rates of major malformation in live-born infants [adjusted odds ratios (aOR): zanamivir 0.37 (95% confidence interval 0.02-2.70); oseltamivir aOR 0.81 (0.05, 14.15)], preterm delivery [aOR: zanamivir 0.95 (0.45, 1.89); oseltamivir aOR 1.68 (0.38, 5.38)] or low birth weight [aOR: zanamivir 0.94 (0.25, 2.90); oseltamivir aOR 4.12 (0.59, 17.99)] were observed following exposure at any gestation. No major malformations were reported in 37 zanamivir or eight oseltamivir first trimester exposures. CONCLUSION: These surveillance data do not provide a signal that use of zanamivir or oseltamivir in pregnancy is associated with an increased risk of the adverse pregnancy outcomes studied but the data are too limited to state conclusively that there is no increase in risk.
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Antivirales/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Oseltamivir/uso terapéutico , Pandemias , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo , Zanamivir/uso terapéutico , Adolescente , Adulto , Antivirales/efectos adversos , Monitoreo Epidemiológico , Femenino , Humanos , Persona de Mediana Edad , Oseltamivir/efectos adversos , Embarazo , Estudios Prospectivos , Reino Unido , Adulto Joven , Zanamivir/efectos adversosRESUMEN
OBJECTIVES: To investigate auditory dysfunction in patients with tinnitus and normal hearing thresholds using two sensitive audiological measures. DESIGN: The study was designed to investigate the characteristics of Audioscan and DPOAE tests in tinnitus patients with normal hearing thresholds. Audioscan and DPOAE notches were analysed and compared. All tests were performed in a sound-treated chamber or in a sound-treated room. STUDY SAMPLE: Forty-five tinnitus patients with normal hearing thresholds were examined following a written clinical protocol. RESULTS: The averaged hearing levels obtained from tinnitus participants were significantly worse at high frequencies than those derived from the normative data. There was a significantly higher prevalence of Audioscan and DPOAE notches, whose central frequencies matched tinnitus frequencies in the mid-frequency regions, but not in the low- and high-frequency regions. A significant correlation was found between the centre frequencies of the Audioscan notches and the DPOAE notches from 500 to 4000 Hz. CONCLUSION: Tinnitus in different frequency regions may be associated with different underlying mechanisms of tinnitus generation. Some negative results on the Audioscan and DPOAE notches matching tinnitus pitches may be due to a limited set of discrete frequencies used for the tinnitus pitch matching test.
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Audiometría de Tonos Puros/métodos , Umbral Auditivo/fisiología , Otoscopía/métodos , Discriminación de la Altura Tonal/fisiología , Acúfeno/diagnóstico , Acúfeno/fisiopatología , Adulto , Audiometría de Tonos Puros/normas , Enfermedades Cocleares/complicaciones , Enfermedades Cocleares/diagnóstico , Enfermedades Cocleares/fisiopatología , Femenino , Audición/fisiología , Humanos , Masculino , Persona de Mediana Edad , Emisiones Otoacústicas Espontáneas/fisiología , Otoscopía/normas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Acúfeno/etiología , Adulto JovenRESUMEN
BACKGROUND: Cytochrome P450 2C19 (CYP2C19) is the principal enzyme responsible for converting clopidogrel into its active metabolite, and common genetic variants have been identified, most notably CYP2C19*2 and CYP2C19*17, that are believed to alter its activity and expression, respectively. OBJECTIVE: We evaluated whether the consequences of the CYP2C19*2 and CYP2C19*17 variants on clopidogrel response were independent of each other or genetically linked through linkage disequilibrium (LD). PATIENTS/METHODS: We genotyped the CYP2C19*2 and CYP2C19*17 variants in 621 members of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study and evaluated the effects of these polymorphisms singly and then jointly, taking into account LD, on clopidogrel prodrug level, clopidogrel active metabolite level, and adenosine 5'-diphosphate (ADP)-stimulated platelet aggregation before and after clopidogrel exposure. RESULTS: The CYP2C19*2 and CYP2C19*17 variants were in LD (|D'| = 1.0; r(2) = 0.07). In association analyses that did and did not account for the effects of CYP2C19*17, CYP2C19*2 was strongly associated with levels of clopidogrel active metabolite (ß = -5.24, P = 3.0 × 10(-9) and ß = -5.36, P = 3.3 × 10(-14) , respectively) and posttreatment ADP-stimulated platelet aggregation (ß = 7.55, P = 2.9 × 10(-16) and ß = 7.51, P = 7.0 × 10(-15) , respectively). In contrast, CYP2C19*17 was marginally associated with clopidogrel active metabolite levels and ADP-stimulated platelet aggregation before (ß = 1.57, P = 0.04 and ß = -1.98, P = 0.01, respectively) but not after (ß = 0.40, P = 0.59 and ß = -0.13, P = 0.69, respectively) adjustment for the CYP2C19*2 variant. Stratified analyses of CYP2C19*2/CYP2C19*17 genotype combinations revealed that CYP2C19*2, and not CYP2C19*17, was the primary determinant in altering clopidogrel response. CONCLUSIONS: Our results suggest that CYP2C19*17 has a small (if any) effect on clopidogrel-related traits and that the observed effect of this variant is due to LD with the CYP2C19*2 loss-of-function variant.
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Hidrocarburo de Aril Hidroxilasas/genética , Inhibidores de Agregación Plaquetaria/farmacología , Ticlopidina/análogos & derivados , Adulto , Clopidogrel , Citocromo P-450 CYP2C19 , Humanos , Persona de Mediana Edad , Farmacogenética , Ticlopidina/farmacologíaRESUMEN
OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Exposición Materna/efectos adversos , Resultado del Embarazo/epidemiología , Teratógenos , Anomalías Inducidas por Medicamentos/epidemiología , Aborto Inducido/estadística & datos numéricos , Aborto Espontáneo/epidemiología , Adulto , Tasa de Natalidad , Estudios de Casos y Controles , Europa (Continente)/epidemiología , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Edad Materna , Embarazo , Primer Trimestre del Embarazo , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate if pelvic or hip width predisposed women to developing greater trochanteric pain syndrome (GTPS). DESIGN: Prospective case control study. PARTICIPANTS: Four groups were included in the study: those gluteal tendon reconstructions (n=31, GTR), those with conservatively managed GTPS (n=29), those with hip osteoarthritis (n=20, OA) and 22 asymptomatic participants (ASC). METHODS: Anterior-posterior pelvic x-rays were evaluated for femoral neck shaft angle; acetabular index, and width at the lateral acetabulum, and the superior and lateral aspects of the greater trochanter. Body mass index, and waist, hip and greater trochanter girth were measured. Data were analysed using a one-way analysis of variance (ANOVA; posthoc Scheffe analysis), then multivariate analysis. RESULTS: The GTR group had a lower femoral neck shaft angle than the other groups (p=0.007). The OR (95% CI) of having a neck shaft angle of less than 134°, relative to the ASC group: GTR=3.33 (1.26 to 8.85); GTPS=1.4 (0.52 to 3.75); OA=0.85 (0.28 to 2.61). The OR of GTR relative to GTPS was 2.4 (1.01 to 5.6). No group difference was found for acetabular or greater trochanter width. Greater trochanter girth produced the only anthropometric group difference (mean (95% CI) in cm) GTR=103.8 (100.3 to 107.3), GTPS=105.9 (100.2 to 111.6), OA=100.3 (97.7 to 103.9), ASC=99.1 (94.7 to 103.5), (ANOVA: p=0.036). Multivariate analysis confirmed adiposity is associated with GTPS. CONCLUSION: A lower neck shaft angle is a risk factor for, and adiposity is associated with, GTPS in women.