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1.
Artigo em Inglês | MEDLINE | ID: mdl-33571606

RESUMO

Methadone maintenance treatment (MMT) is the most common treatment for opioid-dependent pregnant women worldwide. Despite its widespread use, MMT is associated with a variety of adverse neurodevelopmental outcomes in exposed offspring, particularly cognitive impairments. The neurobiological abnormalities underlying these cognitive impairments are, however, poorly understood. This is, in part, due to a lack of animal models that represents the standard of care that methadone is administered in the clinic, with inconsistencies in the timing, doses and durations of treatment. Here we describe the characterisation of a clinically relevant rat model of MMT in which the long-term behavioural and neurobiological effects of prenatal methadone exposure can be assessed in adolescent offspring. Female Sprague-Dawley rats were treated orally with an ascending methadone dosage schedule (5, 10, 15, 20, 25 and 30 mg/kg/day), self-administered in drinking water prior to conception, throughout gestation and lactation. Pregnancy success, maternal gestational weight gain, litter survival and size were not significantly altered in methadone-exposed animals. Methadone-exposed offspring body and brain weights were significantly lower at birth. Novel object recognition tests performed at adolescence revealed methadone-exposed offspring had impaired recognition memory. Furthermore, the rewarded T-maze alternation task demonstrated that methadone-exposed female, but not male, offspring also exhibit working memory and learning deficits. Immunoblots of the adolescent prefrontal cortex and hippocampus showed methadone-exposed offspring displayed reduced levels of mature BDNF, in addition to the GABAergic proteins, GAD67 and parvalbumin, in a sex- and brain region-specific fashion. This rat model closely emulates the clinical scenario in which methadone is administered to opioid-dependent pregnant woman and provides evidence MMT can cause cognitive impairments in adolescent offspring that may be underlined by perturbed neurodevelopment of the GABAergic system.


Assuntos
Analgésicos Opioides/efeitos adversos , Cognição/efeitos dos fármacos , Neurônios GABAérgicos/efeitos dos fármacos , Metadona/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Analgésicos Opioides/administração & dosagem , Animais , Encéfalo/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metadona/administração & dosagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Sprague-Dawley
2.
BMJ Open Qual ; 7(3): e000416, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30246157

RESUMO

INTRODUCTION: Nurses' perceptions of the utility of capnography monitoring are inconsistent in previous studies. We sought to outline the limitations of a uniform education effort in bringing about consistent views of capnography among nurses. METHODS: A survey was administered to 22 nurses in three subacute care floors participating in a pragmatic clinical trial employing capnography monitoring in a large, urban tertiary care hospital. A 5-point Likert scale was used to assess the value and acceptance nurses ascribed to the practice. Means and SD were calculated for each response. RESULTS: Survey results indicated inconsistency in the valuation of capnography, coupled with varying degrees of acceptance of its use. The mean for the level of perceived impact of capnography use on patient safety was 3.86, yet the perceived risk of removing capnography was represented by a mean of 2.57. The levels of urgency attached to apnoea alarms (mean 3.57, SD 1.57) were lower than those for alarms for oxygen saturation violations (mean 3.67, SD 1.32). The necessity for pulse oximetry monitoring was perceived as much higher than that for capnography monitoring (mean 1.76, SD 1.34), where '1' represented pulse oximetry as more necessary and '5' represented capnography as more necessary. CONCLUSIONS: Nursing acceptance of capnography monitoring is a difficult endpoint to achieve. There is a need for better accounting for the external and internal influences on nurse perceptions and values to have greater success with the implementation of similar monitoring.

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