993 resultados para Immediate-Early


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Background and Aims: Submucosal injection of a viscoelastic solution prolongs submucosal lift, thus, facilitating endoscopic mucosal resection. Our objective was to assess the safety and clinical effectiveness of 0.4% hydroxypropyl methylcellulose (HPMC) as a submucosal injectant for endoscopic mucosal resection. Patients and Methods: A prospective, open-label, multicenter, phase 2 study was conducted at 2 academic institutions in Brazil. Eligible participants included patients with early gastrointestinal tumors larger than 10 mm. Outcomes evaluated included complete resection rates, volume of HPMC injected, duration of the submucosal cushion as assessed visually, histology of the resected leisons, and complication rates. Results: Over a 12-month period, 36 eligible patients with superficial neoplastic lesions (stomach 14, colon 11, rectum 5, esophagus 3, duodenum 3) were prospectively enrolled in the study. The mean size of the resected specimen was 20.4 mm (10 to 60 mm). The mean volume of 0.4% HPMC injected was 10.7 mL (range 4 to 35 mL). The mean duration of the submucosal fluid cushion was 27 minutes (range 9 to 70 min). Complete resection was successfully completed in 89%. Five patients (14%) developed immediate bleeding requiring endoclip and APC application. Esophageal perforation occurred in 1 patient requiring surgical intervention. There were no local or systemic adverse events related to HPMC use over the follow-up period (mean 2.2 mo). Conclusion: HPMC solution (0.4%) provides an effective submucosal fluid cushion and is safe for endoscopic resection of early gastrointestinal neoplastic lesions.

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Aims: To evaluate the C-reactive protein (CRP) and interleukin-6 (IL-6) as diagnostic tools for early onset infection in preterm infants with early respiratory distress (RD). Methods: CRP and IL-6 were quantified at identification of RD and 24 h after in 186 newborns. Effects of maternal hypertension, mode of delivery, Apgar score, birth weight, gestational age, mechanical ventilation, being small for gestational age (SGA), and the presence of infection were analyzed. Results: Forty-four infants were classified as infected, 42 as possibly infected, and 100 as uninfected. Serum levels of IL-6 (0 h), CRP (0 h), and CRP (24 h), but not IL-6 (24 h) were significantly higher in infected infants compared to the remaining groups. The best test for identification of infection was the combination of IL-6 (0 h) 36 pg/dL and/or CRP (24 h) 0.6 mg/dL, which yielded 93% sensitivity and 37% specificity. The presence of infection and vaginal delivery independently increased IL-6 (0 h), CRP (0 h) and CRP (24 h) levels. Being SGA also increased the CRP (24 h) levels. IL-6 (24 h) was independently increased by mechanical ventilation. Conclusions: The combination of IL-6 (0 h) and/or CRP (24 h) is helpful for excluding early onset infection in preterm infants with RD but the poor specificity limits its potential benefit as a diagnostic tool.

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Most sugarcane breeding programs in Australia use large unreplicated trials to evaluate clones in the early stages of selection. Commercial varieties that are replicated provide a method of local control of soil fertility. Although such methods may be useful in detecting broad trends in the field, variation often occurs on a much smaller scale. Methods such as spatial analysis adjust a plot for variability by using information from immediate neighbours. These techniques are routinely used to analyse cereal data in Australia and have resulted in increased accuracy and precision in the estimates of variety effects. In this paper, spatial analyses in which the variability is decomposed into local, natural, and extraneous components are applied to early selection trials in sugarcane. Interplot competition in cane yield and trend in sugar content were substantial in many of the trials and there were often large differences in the selections between the spatial and current method used by the Bureau of Sugar Experiment Stations. A joint modelling approach for tonnes sugar per hectare in response to fertility trends and interplot competition is recommended.

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Peripheral arterial disease (PAD) is a common disease with increasing prevalence, presenting with impaired walking ability affecting patient's quality of life. PAD epidemiology is known, however, mechanisms underlying functional muscle impairment remain unclear. Using a mouse PAD model, aim of this study was to assess muscle adaptive responses during early (1 week) and late (5 weeks) disease stages. Unilateral hindlimb ischemia was induced in ApoE(-/-) mice by iliac artery ligation. Ischemic limb perfusion and oxygenation (Laser Doppler imaging, transcutaneous oxygen pressure assessments) significantly decreased during early and late stage compared to pre-ischemia, however, values were significantly higher during late versus early phase. Number of arterioles and arteriogenesis-linked gene expression increased at later stage. Walking ability, evaluated by forced and voluntary walking tests, remained significantly decreased both at early and late phase without any significant improvement. Muscle glucose uptake ([18F]fluorodeoxyglucose positron emission tomography) significantly increased during early ischemia decreasing at later stage. Gene expression analysis showed significant shift in muscle M1/M2 macrophages and Th1/Th2 T cells balance toward pro-inflammatory phenotype during early ischemia; later, inflammatory state returned to neutrality. Muscular M1/M2 shift inhibition by a statin prevented impaired walking ability in early ischemia. High-energy phosphate metabolism remained unchanged (31-Phosphorus magnetic resonance spectroscopy). Results show that rapid transient muscular inflammation contributes to impaired walking capacity while increased glucose uptake may be a compensatory mechanisms preserving immediate limb viability during early ischemia in a mouse PAD model. With time, increased ischemic limb perfusion and oxygenation assure muscle viability although not sufficiently to improve walking impairment. Subsequent decreased muscle glucose uptake may partly contribute to chronic walking impairment. Early inflammation inhibition and/or late muscle glucose impairment prevention are promising strategies for PAD management.

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Purpose: Epilepsy surgery in young children with focal lesions offers a unique opportunity to study the impact of severe seizures on cognitive development during a period of maximal brain plasticity, if immediate control can be obtained. We studied 11 children with early refractory epilepsy (median onset, 7.5 months) due to focal lesion who were rendered seizure-free after surgery performed before the age of 6 years. Methods: The children were followed prospectively for a median of 5 years with serial neuropsychological assessments correlated with electroencephalography (EEG) and surgery-related variables. Results: Short-term follow-up revealed rapid cognitive gains corresponding to cessation of intense and propagated epileptic activity [two with early catastrophic epilepsy; two with regression and continuous spike-waves during sleep (CSWS) or frontal seizures]; unchanged or slowed velocity of progress in six children (five with complex partial seizures and frontal or temporal cortical malformations). Longer-term follow-up showed stabilization of cognitive levels in the impaired range in most children and slow progress up to borderline level in two with initial gains. Discussion: Cessation of epileptic activity after early surgery can be followed by substantial cognitive gains, but not in all children. In the short term, lack of catch-up may be explained by loss of retained function in the removed epileptogenic area; in the longer term, by decreased intellectual potential of genetic origin, irreversible epileptic damage to neural networks supporting cognitive functions, or reorganization plasticity after early focal lesions. Cognitive recovery has to be considered as a "bonus," which can be predicted in some specific circumstances.

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BACKGROUND: Invasive fungal infection (IFI) is associated with high mortality after heart transplantation (HTx). After two undiagnosed fatal cases of early disseminated fungal infections in our heart transplant program, a retrospective analysis was conducted to identify risk factors for the development of IFI and implement a new antifungal prophylaxis policy. METHODS: Clinical characteristics of HTx recipients hospitalized in our center (2004-2010) were recorded (Period 1), and risk factors associated with IFI were investigated using Cox regression analysis. From October 2010 to October 2012 (Period 2), targeted caspofungin prophylaxis was administered to all recipients at high risk for IFI, based on the results of the Period 1 analysis. RESULTS: During Period 1, 10% (6/59) of the patients developed IFI at a median onset of 9 days after transplantation. By multivariate analysis, the use of posttransplant extracorporeal membrane oxygenation (ECMO) was the strongest predictor for fungal infection (OR, 29.93; 95% CI, 1.51-592.57, P=0.03), whereas renal replacement therapy (RRT) and Aspergillus colonization were significant predictors only by univariate analysis. During Period 2, only 4% (1/26) of the patients developed IFI. In patients at high risk for IFI, antifungal prophylaxis was administered to 17% (4/23) in Period 1 versus 100% (13/13) in Period 2 (P<0.01). By survival analysis, antifungal prophylaxis was associated with a reduction in 90-day IFI incidence (HR, 0.14; 95% CI, 0.03-0.84, P=0.03) and 30-day mortality (HR, 0.25; 95% CI, 0.09-0.8, P=0.02). CONCLUSION: Extracorporeal membrane oxygenation was identified an important risk factor for IFI after HTx, and its use may require targeted administration of antifungal prophylaxis in the immediate posttransplant period.

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Flexible intramedullary nailing (FIN) is the gold standard treatment for femur fracture in school-aged children. It has been performed successfully in younger children, although Spica cast immobilisation (SCI) has been the most widely used strategy to date. METHOD: A retrospective analysis was performed between two comparable groups of children aged 1-4 years with a femoral shaft fracture. Two University hospitals, each using specific treatment guidelines, participated in the study: SCI in Group I (Basel, Switzerland) and FIN in Group II (Lausanne, Switzerland). RESULTS: Group I included 19 children with a median age of 26 months (range 12-46 months). Median hospital stay was 1 day (range 0-5 days) and casts were retained for a median duration of 21 days (range 12-29 days). General anaesthesia was used in six children and sedation in four. Skin breakdown secondary to cast irritation occurred in two children (10.5%). The median follow-up was 114 months (range 37-171 months). No significant malunion was noted. Group II included 27 children with a median age of 38.4 months (range 18.7-46.7 months). Median hospital stay was 4 days (range 1-13 days). All children required general anaesthesia for insertion and removal of the nails. Free mobilisation and full weight bearing were allowed at a median of 2 days (range 1-10 days) and 7 days (range 1-30 days), respectively, postoperatively. Nail exteriorisation was noted in three children (11%). The median follow-up was 16.5 months (range 8-172 months). No significant malunion was reported. CONCLUSIONS: Young children with a femoral shaft fracture treated by SCI or FIN had similarly favourable outcomes and complication rates. FIN allowed earlier mobilisation and full weight bearing. Compared to SCI, a greater number of children required general anaesthesia. In a pre-school child with a femoral shaft fracture, immediate SCI applied by a paediatric orthopaedic team following specific guidelines allowed early discharge from hospital with few complications.

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Delayed recovery has been advocated to limit the postoperative stress linked to awakening from anesthesia, but data on this subject are lacking. In this study, we measured oxygen consumption (V(O2)) and plasma catecholamine concentrations as markers of postoperative stress. We tested the hypothesis that delayed recovery and extubation would attenuate metabolic changes after intracranial surgery. Thirty patients were included in a prospective, open study and were randomized into two groups. In Group I, the patients were tracheally extubated as soon as possible after surgery. In Group II, the patients were sedated with propofol for 2 h after surgery. V(O2), catecholamine concentration, mean arterial pressure (MAP), and heart rate (HR) were measured during anesthesia, at extubation, and 30 min after extubation. V(O2) and noradrenaline on extubation and mean V(O2) during recovery were significantly higher in Group II than in Group I (V(O2) for Group I: preextubation 215 +/- 46 mL/min, recovery 198 +/- 38 mL/min; for Group II: preextubation 320 +/- 75 mL/min, recovery 268 +/- 49 mL/min; noradrenaline on extubation for Group I: 207 +/- 76 pg/mL, for Group II: 374 +/- 236 pg/ mL). Extubation induced a significant increase in MAP. MAP, HR, and adrenaline values were not statistically different between groups. In conclusion, delayed recovery after neurosurgery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence from general anesthesia. IMPLICATIONS: In this study, we tested the hypothesis that delayed recovery after neurosurgery would attenuate the consequences of recovery from general anesthesia. As markers of stress, oxygen consumption and noradrenaline blood levels were higher after delayed versus early recovery. Thus, delayed recovery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence after neurosurgery.

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Marine environments are frequently exposed to oil spills as a result of transportation, oil drilling or fuel usage. Whereas large oil spills and their effects have been widely documented, more common and recurrent small spills typically escape attention. To fill this important gap in the assessment of oil-spill effects, we performed two independent supervised full sea releases of 5 m(3) of crude oil, complemented by on-board mesocosm studies and sampling of accidentally encountered slicks. Using rapid on-board biological assays, we detect high bioavailability and toxicity of dissolved and dispersed oil within 24 h after the spills, occurring fairly deep (8 m) below the slicks. Selective decline of marine plankton is observed, equally relevant for early stages of larger spills. Our results demonstrate that, contrary to common thinking, even small spills have immediate adverse biological effects and their recurrent nature is likely to affect marine ecosystem functioning.

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Western societies have been faced with the fact that overweight, impaired glucose regulation and elevated blood pressure are already prevalent in pediatric populations. This will inevitably mean an increase in later manifestations of cardio-metabolic diseases. The dilemma has been suggested to stem from fetal life and it is surmised that the early nutritional environment plays an important role in the process called programming. The aim of the present study was to characterize early nutritional determinants associating with cardio-metabolic risk factors in fetuses, infants and children. Further, the study was designated to establish whether dietary counseling initiated in early pregnancy can modify this cascade. Healthy mother-child pairs (n=256) participating in a dietary intervention study were followed from early pregnancy to childhood. The intervention included detailed dietary counseling by a nutritionist targeting saturated fat intake in excess of recommendations and fiber consumption below recommendations. Cardio-metabolic programming was studied by characterizing the offspring’s cardio-metabolic risk factors such as over-activation of the autonomic nervous system, elevated blood pressure and adverse metabolic status (e.g. serum high split proinsulin concentration). Fetal cardiac sympathovagal activation was measured during labor. Postnatally, children’s blood pressure was measured at six-month and four-year follow-up visits. Further, infants’ metabolic status was assessed by means of growth and serum biomarkers (32-33 split proinsulin, leptin and adiponectin) at the age of six months. This study proved that fetal cardiac sympathovagal activity was positively associated with maternal pre-pregnancy body mass index indicating adverse cardio-metabolic programming in the offspring. Further, a reduced risk of high split proinsulin in infancy and lower blood pressure in childhood were found in those offspring whose mothers’ weight gain and amount and type of fats in the diet during pregnancy were as recommended. Of note, maternal dietary counseling from early pregnancy onwards could ameliorate the offspring’s metabolic status by reducing the risk of high split proinsulin concentration, although it had no effect on the other cardio-metabolic markers in the offspring. At postnatal period breastfeeding proved to entail benefits in cardio-metabolic programming. Finally, the recommended dietary protein and total fat content in the child’s diet were important nutritional determinants reducing blood pressure at the age of four years. The intrauterine and immediate postnatal period comprise a window of opportunity for interventions aiming to reduce the risk of cardio-metabolic disorders and brings the prospect of achieving health benefits over one generation.

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Complex interactions between androgen and estrogen (E2) regulate prostatic development and physiology. We analyzed the early effects of a high single dose of E2 (25 mg/kg body weight) and castration (separately or combined) on the adult 90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight, and the variation in the relative and absolute volume of tissue compartments and apoptotic indices were determined for 7 days. Castration and exogenous E2 markedly reduced ventral prostate weight (about 50% of the control), with a significant reduction in the epithelial compartment and increased stroma. The final volume of the epithelium was identical at day 7 for all treatments (58.5% of the control). However, E2 had an immediate effect, causing a reduction in epithelial volume as early as day 1. An increase in smooth muscle cell volume resulted from the concentration of these cells around the regressing epithelium. The treatments resulted in differential kinetics in epithelial cell apoptosis. Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells presenting signs of apoptosis, whereas E2 caused an immediate increase (observed on day 1) and a sustained (up to day 7) effect. E2 administration to castrated rats significantly increased the level of apoptosis by day 3, reaching 9% of the epithelial cells. The divergent kinetics between treatments resulted in the same levels of epithelial regression after 7 days (~30% of control). These results show that E2 has an immediate and possibly direct effect on the prostate, and anticipates epithelial cell death before reducing testosterone to levels as low as those of castrated rats. In addition, E2 and androgen deprivation apparently cause epithelial cell death by distinct and independent pathways.

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Methods for reliable evaluation of spinal cord (SC) injury in rats at short periods (2 and 24 h) after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a) anesthesia, b) dissection of soft prevertebral tissue, and c) laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their potential for the study of cellular mechanisms of primary injury and repair after traumatic SC injury.

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This study aimed to demonstrate that congenital diaphragmatic hernia (CDH) results in vascular abnormalities that are directly associated with the severity of pulmonary hypoplasia and hypertension. These events increase right ventricle (RV) afterload and may adversely affect disease management and patient survival. Our objective was to investigate cardiac function, specifically right ventricular changes, immediately after birth and relate them to myocardial histological findings in a CDH model. Pregnant New Zealand rabbits underwent the surgical procedure at 25 days of gestation (n=14). CDH was created in one fetus per horn (n=16), and the other fetuses were used as controls (n=20). At term (30 days), fetuses were removed, immediately dried and weighed before undergoing four-parameter echocardiography. The lungs and the heart were removed, weighed, and histologically analyzed. CDH animals had smaller total lung weight (P<0.005), left lung weight (P<0.005), and lung-to-body ratio (P<0.005). Echocardiography revealed a smaller left-to-right ventricle ratio (LV/RV, P<0.005) and larger diastolic right ventricle size (DRVS, P<0.007). Histologic analysis revealed a larger number of myocytes undergoing mitotic division (186 vs 132, P<0.05) in CDH hearts. Immediate RV dilation of CDH hearts is related to myocyte mitosis increase. This information may aid the design of future strategies to address pulmonary hypertension in CDH.

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L’objectif de cette thèse est d’élucider l’intention, la pertinence et la cohérence de l’appropriation par Heidegger des concepts principaux de la philosophie pratique aristotélicienne dans ses premiers cours. Notre analyse portera principalement sur les notions clefs d’energeia et de phronēsis. La première section de la thèse est préparatoire : elle est consacrée à une analyse étroite des textes pertinents de l’Éthique à Nicomaque, mais aussi de la Métaphysique, en discussion avec d’autres commentateurs modernes. Cette analyse jette les fondations philologiques nécessaires en vue d’aborder les audacieuses interprétations de Heidegger sur une base plus ferme. La deuxième et principale section consiste en une discussion de l’appropriation ontologique de l’Éthique à Nicomaque que Heidegger entreprend de 1922 à 1924, à partir des textes publiés jusqu’à ce jour et en portant une attention spéciale à Métaphysique IX. Le résultat principal de la première section est un aperçu du caractère central de l’energeia pour le projet d’Aristote dans l’Éthique à Nicomaque et, plus spécifiquement, pour sa compréhension de la praxis, qui dans son sens original s’avère être un mode d’être des êtres humains. Notre analyse reconnaît trois traits essentiels de l’energeia et de la praxis, deux desquels provenant de l’élucidation aristotélicienne de l’energeia dans Métaphysique IX 6, à savoir son immédiateté et sa continuité : energeia exprime l’être comme un « accomplissement immédiat mais inachevé ». L’irréductibilité, troisième trait de l’energeia et de la praxis, résulte pour sa part de l’application de la structure de l’energeia à la caractérisation de la praxis dans l’Éthique à Nicomaque, et du contraste de la praxis avec la poiēsis et la theōria. Ces trois caractéristiques impliquent que la vérité pratique ― la vérité de la praxis, ce qui est l’ « objet » de la phronēsis ― ne peut être à proprement parler possédée et ainsi transmise : plus qu’un savoir, elle se révèle surtout comme quelque chose que nous sommes. C’est ce caractère unique de la vérité pratique qui a attiré Heidegger vers Aristote au début des années 1920. La deuxième section, consacrée aux textes de Heidegger, commence par la reconstruction de quelques-uns des pas qui l’ont conduit jusqu’à Aristote pour le développement de son propre projet philosophique, pour sa part caractérisé par une profonde, bien qu’énigmatique combinaison d’ontologie et de phénoménologie. La légitimité et la faisabilité de l’appropriation clairement ontologique de l’Éthique à Nicomaque par Heidegger est aussi traitée, sur la base des résultats de la première section. L’analyse de ces textes met en lumière la pénétrante opposition établie par Heidegger entre la phronēsis et l’energeia dans son programmatique Natorp Bericht en 1922, une perspective qui diverge fortement des résultats de notre lecture philologique d’Aristote dans la première section. Cette opposition est maintenue dans nos deux sources principales ― le cours du semestre d’hiver 1924-25 Platon: Sophistes, et le cours du semestre d’été 1924 Grundbegriffe der aristotelischen Philosophie. Le commentaire que Heidegger fait du texte d’Aristote est suivi de près dans cette section: des concepts tels que energeia, entelecheia, telos, physis ou hexis ― qui trouvent leur caractérisation ontologique dans la Métaphysique ou la Physique ― doivent être examinés afin de suivre l’argument de Heidegger et d’en évaluer la solidité. L’hypothèse de Heidegger depuis 1922 ― à savoir que l’ontologie aristotélicienne n’est pas à la hauteur des aperçus de ses plus pénétrantes descriptions phénoménologiques ― résulte en un conflit opposant phronēsis et sophia qui divise l’être en deux sphères irréconciliables qui auraient pour effet selon Heidegger de plonger les efforts ontologiques aristotéliciens dans une impasse. Or, cette conclusion de Heidegger est construite à partir d’une interprétation particulière de l’energeia qui laisse de côté d’une manière décisive son aspect performatif, pourtant l’un des traits essentiels de l’energeia telle qu’Aristote l’a conçue. Le fait que dans les années 1930 Heidegger ait lui-même retrouvé cet aspect de l’energeia nous fournit des raisons plus fortes de mettre en doute le supposé conflit entre ontologie et phénoménologie chez Aristote, ce qui peut aboutir à une nouvelle formulation du projet heideggérien.

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Background: The aim of this study was to evaluate stimulant medication response following a single dose of methylphenidate (MPH) in children and young people with hyperkinetic disorder using infrared motion analysis combined with a continuous performance task (QbTest system) as objective measures. The hypothesis was put forward that a moderate testdose of stimulant medication could determine a robust treatment response, partial response and non-response in relation to activity, attention and impulse control measures. Methods: The study included 44 children and young people between the ages of 7-18 years with a diagnosis of hyperkinetic disorder (F90 & F90.1). A single dose-protocol incorporated the time course effects of both immediate release MPH and extended release MPH (Concerta XL, Equasym XL) to determine comparable peak efficacy periods post intake. Results: A robust treatment response with objective measures reverting to the population mean was found in 37 participants (84%). Three participants (7%) demonstrated a partial response to MPH and four participants (9%) were determined as non-responders due to deteriorating activity measures together with no improvements in attention and impulse control measures. Conclusion: Objective measures provide early into prescribing the opportunity to measure treatment response and monitor adverse reactions to stimulant medication. Most treatment responders demonstrated an effective response to MPH on a moderate testdose facilitating a swift and more optimal titration process.