Compatibility and Stability of Morphine Sulphate and Naloxone Hydrochloride in 0.9% Sodium Chloride for Injection

ABSTRACTBackground: Naloxone may be administered in conjunction with morphine to reduce the risk of opioid-induced pruritis. Combining these drugs for coadministration may be beneficial, but little is known about their physical compatibility and stability in combined solutions.Objective: To describe the physical compatibility and stability of morphine sulphate and naloxone hydrochloride (at various concentrations) in IV admixtures.Methods:The physical compatibility and stability of admixtures of morphine 1000 μg/mL and naloxone 4 μg/mL, 12.5 μg/mL, and 25 μg/mL in 0.9% sodium chloride were studied. For each concentration of naloxone, one bag was stored at room temperature (22°C) for 72 h and one bag was stored under refrigeration (4°C) for 30 days. For all preparations, physical characteristics, including pH, colour, and formation of precipitate, were evaluated. The samples were also analyzed by a stability-indicating high-performance liquid chromatographic method. Stability was defined as the retention of at least 90% of the initial concentration.Results: No notable changes in pH or colour and no macroprecipitation were observed in any of the preparations after storage at 22°C for up to 72 h or at 4°C for up to 30 days. All preparations maintained more than 90% of the initial concentrations of morphine and naloxone at the end of the respective study periods. The calculated lower limit of the 95% confidence interval also indicated that 90% or more of the initial concentration remained at the end of each study period.Conclusion: Admixtures of morphine sulphate and naloxone hydrochloride were stable for 72 h at room temperature and for 30 days with refrigeration.RÉSUMÉContexte : La naloxone peut être administrée en concomitance avec la morphine pour réduire le risque de prurit induit par les opioïdes. L’association de ces médicaments pour leur administration concomitante peut être bénéfique, mais on ne sait que peu de choses sur leur compatibilité physique et leur stabilité dans des solutions combinées.Objectif : Décrire la compatibilité physique et la stabilité du sulfate de morphine et du chlorhydrate de naloxone (à diverses concentrations) mélangés dans des solutions pour administration i.v.Méthodes : La compatibilité physique et la stabilité des mélanges de morphine à 1000 μg/mL et de naloxone à 4 μg/mL, 12,5 μg/mL et 25 μg/mL dans du chlorure de sodium à 0,9 % ont été étudiées. Pour chaque concentration de naloxone, on a entreposé un sac à la température ambiante (22 °C) pendant 72 heures et un autre au réfrigérateur (4 °C) pendant 30 jours. Les propriétés physiques, notamment le pH, la couleur et la formation de précipité, ont été évaluées pour toutes les préparations. Les échantillons ont aussi été analysés à l’aide d’une épreuve validée mesurant la stabilité par chromatographie liquide haute performance. La stabilité a été définie comme étant la rétention d’au moins 90 % de la concentration initiale des agents.Résultats : Aucun changement notable du pH ou de la couleur et aucune formation de macroprécipité n’ont été observés dans l’ensemble des préparations qui ont été conservées à une température de 22 °C pendant un maximum de 72 heures ou à une température de 4 °C pendant un maximum de 30 jours. Toutes les préparations ont conservé plus de 90 % de leurs concentrations initiales de morphine et de naloxone à la fin de leurs périodes d’étude respectives. La limite inférieure de l’intervalle de confiance à 95 % indiquait également que 90 % ou plus de la concentration initiale subsistait à la fin de chaque période d’étude.Conclusion: Les mélanges de sulfate de morphine et de chlorhydrate de naloxone sont demeurés stables pendant 72 heures à la température ambiante et pendant 30 jours lorsqu’ils étaient réfrigérés

Promotion of self-regulated learning in classrooms:investigating frequency, quality, and consequences for student performance

An implication of the current research on self-regulation is to implement the promotion of self-regulated learning in schools. Teachers can promote self-regulated learning either directly by teaching learning strategies or indirectly by arranging a learning environment that enables students to practise self-regulation. This study investigates teachers' direct and indirect promotion of self-regulated learning and its relation to the development of students' performance. Twenty German mathematics teachers with their overall 538 students (grade 9) were videotaped for a three-lesson unit on the Pythagorean Theorem. Students' mathematics performance was tested several times before and after the observed lessons. A low-inferent coding system was applied to assess the teachers' implicit or explicit instruction of cognitive strategies (e.g., organisation), metacognitive strategies (e.g., planning), and motivational strategies (e.g., resource management). High-inferent ratings were used to assess features of the learning environment that foster self-regulation. Results reveal that a great amount of strategy teaching takes place in an implicit way, whereas explicit strategy teaching and supportive learning environment are rare. The instruction of organisation strategies and some features of the learning environment (constructivism, transfer) relate positively to students' performance development. In contrast to implicit strategy instruction, explicit strategy instruction was associated with a gain in performance. These results reveal a discrepancy between the usefulness of explicit strategy instruction and its rare occurrence in classrooms

Results of a Randomized Clinical Trial of Speech after Early Neurostimulation in Parkinson's Disease

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Results of a Randomized Clinical Trial of Speech after Early Neurostimulation in Parkinson's Disease

BackgroundThe EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. ObjectiveThis prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. MethodsSTN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. ResultsOver the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. ConclusionAt this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. (c) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society