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OBJECTIVE: Factors associated with the development and expression of Neonatal Opioid Withdrawal Syndrome (NOWS) are poorly understood. There are conflicting data on the role of infant sex in NOWS. Some studies have suggested that infant sex predicts NOWS severity and adverse outcomes, with male infants being more vulnerable. This study aimed to analyze if infant sex is associated with the severity of NOWS among those who require pharmacologic treatment. STUDY DESIGN: This is a retrospective cohort study of term and late-preterm infants (≥35 weeks gestation) exposed to in utero opioids, born between September 2006 and August 2022, and required pharmacologic treatment for NOWS. Maternal and infant demographics were collected. Indicators of the severity of NOWS (duration of medical treatment (DOT), duration of hospitalization, maximum dose of opioid treatment, and use of secondary medications) were compared between male and female infants. Standard statistical tests and regression analysis were used to establish the differences in outcomes after accounting for confounders and baseline differences. RESULTS: Out of the 1,074 infants included in the study, 47.9% were female, and 52.1% were male. There was no significant difference in demographic and baseline clinical characteristics between groups except for anthropometry (birth weight, head circumference, and length) and Apgar score at 5 minutes. The median DOT (25 days [14, 39] vs. 23 days [13, 39], p = 0.57), length of hospital stay (31.5 days [20, 44] vs. 28 days [20, 44], p = 0.35), treatment with phenobarbital (24.7 vs. 26.3%, p = 0.56), and clonidine (3.9 vs. 3.8%, p = 0.9) were similar in both groups. The differences remained nonsignificant after adjusting for birth anthropometric measurements, gestational age, 5-minute Apgar score, small for gestational age status, and maternal exposure to benzodiazepines. CONCLUSION: In this cohort of neonates, sex-related differences were not identified to influence the severity of NOWS among those who required pharmacological treatment. KEY POINTS: · Vulnerability to NOWS is multifactorial.. · The role of infant sex in the severity of NOWS is not concrete.. · We noted that sex did not impact NOWS severity in those treated..
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OBJECTIVES: To compare clinical outcomes for infants with neonatal opioid withdrawal syndrome (NOWS) treated with buprenorphine or morphine. STUDY DESIGN: Retrospective study of infants born ≥35 weeks' gestation and admitted to the NICU for NOWS treatment between 2011 and 2022. Length of treatment, length of stay in the hospital, and the need for secondary medications were compared between buprenorphine and morphine treated neonates. Multiple regression analysis was performed, adjusting for baseline differences and confounders. RESULTS: 417 neonates were treated with morphine and 232 with buprenorphine. The buprenorphine group had shorter treatment days [-10.8 days; 95% CI: -8.08 to -13.53] and shorter hospital stay [-11.8 days; 95% CI: -8.83 to -14.78]. The buprenorphine group was no more likely to receive phenobarbital or clonidine (26% vs. 29%). CONCLUSION: In this large single-center study, buprenorphine was associated with shorter lengths of treatment and hospital stay in the treatment of NOWS compared to morphine.
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Background: Atopic eczema is a common childhood skin problem linked with asthma, food allergy and allergic rhinitis that impairs quality of life. Objectives: To determine whether advising parents to apply daily emollients in the first year can prevent eczema and/or other atopic diseases in high-risk children. Design: A United Kingdom, multicentre, pragmatic, two-arm, parallel-group randomised controlled prevention trial with follow-up to 5 years. Setting: Twelve secondary and four primary care centres. Participants: Healthy infants (at least 37 weeks' gestation) at high risk of developing eczema, screened and consented during the third trimester or post delivery. Interventions: Infants were randomised (1 : 1) within 21 days of birth to apply emollient (Doublebase Gel®; Dermal Laboratories Ltd, Hitchin, UK or Diprobase Cream®) daily to the whole body (excluding scalp) for the first year, plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). Families were not blinded to allocation. Main outcome measures: Primary outcome was eczema diagnosis in the last year at age 2 years, as defined by the UK Working Party refinement of the Hanifin and Rajka diagnostic criteria, assessed by research nurses blinded to allocation. Secondary outcomes up to age 2 years included other eczema definitions, time to onset and severity of eczema, allergic rhinitis, wheezing, allergic sensitisation, food allergy, safety (skin infections and slippages) and cost-effectiveness. Results: One thousand three hundred and ninety-four newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in the emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months. At 2 years, eczema was present in 139/598 (23%) in the emollient group and 150/612 (25%) in controls (adjusted relative risk 0.95, 95% confidence interval 0.78 to 1.16; p = 0.61 and adjusted risk difference -1.2%, 95% confidence interval -5.9% to 3.6%). Other eczema definitions supported the primary analysis. Food allergy (milk, egg, peanut) was present in 41/547 (7.5%) in the emollient group versus 29/568 (5.1%) in controls (adjusted relative risk 1.47, 95% confidence interval 0.93 to 2.33). Mean number of skin infections per child in the first year was 0.23 (standard deviation 0.68) in the emollient group versus 0.15 (standard deviation 0.46) in controls; adjusted incidence rate ratio 1.55, 95% confidence interval 1.15 to 2.09. The adjusted incremental cost per percentage decrease in risk of eczema at 2 years was £5337 (£7281 unadjusted). No difference between the groups in eczema or other atopic diseases was observed during follow-up to age 5 years via parental questionnaires. Limitations: Two emollient types were used which could have had different effects. The median time for starting emollients was 11 days after birth. Some contamination occurred in the control group (< 20%). Participating families were unblinded and reported on some outcomes. Conclusions: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children. Emollient use was associated with a higher risk of skin infections and a possible increase in food allergy. Emollient use is unlikely to be considered cost-effective in this context. Future research: To pool similar studies in an individual patient data meta-analysis. Trial registration: This trial is registered as ISRCTN21528841. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/67/12) and is published in full in Health Technology Assessment; Vol. 28, No. 29. See the NIHR Funding and Awards website for further award information.
Eczema is a troublesome itchy skin condition affecting 1 in 5 children and 1 in 10 UK adults. There is no cure and affected children are more likely to develop food allergies. We wanted to see if we could prevent eczema by protecting the skin of babies at higher risk of developing eczema (with an immediate relative with eczema, asthma or hay fever) with moisturisers used to treat dry skin. Previous research suggested that protecting the skin barrier might also prevent food allergy. One thousand three hundred and ninety-four families took part in a study; half of them were asked to apply moisturiser every day to their newborn baby for the first year and half to look after their baby's skin in the normal way. At the age of 2 years, we did not see any difference in how common eczema was between the two groups: 23% had eczema in the moisturiser group and 25% in the normal care group. It did not matter how we defined eczema whether examined by a researcher or parent report. We did not find any differences in related conditions like asthma or hay fever either. We found that children using moisturisers had seen their doctor slightly more often for mild skin infections. There was a hint that food allergy might have been increased in the moisturiser group, but there was not enough data to be sure. We followed up the children to age 5 years, but we still did not find any benefits from using moisturisers in early life. Since this study, other similar research has been done using newer types of moisturisers, but their results are the same. This study shows that using daily moisturisers on healthy babies with a high risk of eczema does not prevent eczema. It is one less thing for busy families to worry about.
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Análise Custo-Benefício , Eczema , Emolientes , Humanos , Emolientes/uso terapêutico , Feminino , Masculino , Lactente , Recém-Nascido , Eczema/prevenção & controle , Reino Unido , Pré-Escolar , Anos de Vida Ajustados por Qualidade de Vida , Qualidade de Vida , Avaliação da Tecnologia Biomédica , Dermatite Atópica/prevenção & controleRESUMO
Pectobacterium atrosepticum (Pba) is a gram-negative bacterium that causes blackleg and tuber soft rot of potato but can also asymptomatically colonise other (non-host) plant species. The aim of this study was to investigate the molecular processes and responses involved in Pba-host (potato) and Pba-non-host (radish) interactions, under laboratory conditions. To achieve this, we used total mRNA-sequencing to measure the gene expression patterns from all three species: Pba, potato and radish. We employed an end-point dual transcriptome approach. We used hydroponically grown potato (Solanum tuberosum var. Estima) and oil radish (Raphanus sativa var. Bento) roots inoculated with Pba SCRI1039 for 14 days compared to un-inoculated control plants or cultured bacteria. Total RNA was extracted from replicates of the two plant species and the bacterium using a Macherey-Nagel Nucleospin Plant RNA kit. The RNA from the 17 samples was then subjected to total mRNA-sequencing (paired-end) on an Illumina NovaSeq 6000™ sequencing platform. This gave between 39.2-58.1M reads per sample. The high-quality reads obtained were mapped to the corresponding reference genomes using Bowtie2 and the percentages of bacterium and plant transcripts calculated. This dataset constitutes the raw read fastq files and can be used to inform on genes active in plant rhizosphere-microbe interactions.
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Obesity and Type 2 Diabetes Mellitus (T2DM) are chronic conditions with significant personal, societal, and economic impacts. Expanding on existing trial evidence, the NHS piloted a 52-week low-calorie diet programme for T2DM, delivered by private providers using total diet replacement products and behaviour change support. This study aimed to determine the extent to which providers and coaches adhered to the service specification outlined by NHS England. An observational qualitative study was conducted to examine the delivery of both one-to-one and group-based delivery of programme sessions. Observations of 122 sessions across eight programme delivery samples and two service providers were completed. Adherence to the service specification was stronger for those outcomes that were easily measurable, such as weight and blood glucose, while less tangible elements of the specification, such as empowering service users, and person-centred delivery were less consistently observed. One-to-one sessions were more successful in their person-centred delivery, and the skills of the coaches delivering the sessions had a strong impact on adherence to the specification. Overall, the results show that there was variability by provider and delivery mode in the extent to which sessions of the NHS Low-Calorie Diet Programme reflected the intended service specification. In subsequent programmes it is recommended that one-to-one sessions are used, with accompanying peer support, and that providers improve standardised training and quality assurance to ensure specification adherence.
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Restrição Calórica , Diabetes Mellitus Tipo 2 , Medicina Estatal , Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Obesidade/dietoterapia , Feminino , Masculino , Inglaterra , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
OBJECTIVE: Chervoneva et al. (2020) developed an abbreviated score (sMNAS-9) derived from full modified Finnegan MOTHER NAS scale (MNAS) for evaluating severity of NOWS. We sought to develop NOWS treatment algorithms for clinical decision rules based on scores utilizing the shorter sMNAS. STUDY DESIGN: This was a retrospective study of 373 infants with NOWS scored with MNAS and treated with morphine between 2007 and 2016. The infants were randomly split into training/test sets. The training set was used to derive optimized cutoff values for sMNAS-9 scores. The independent set evaluated the sMNAS-9 clinical decision rules based on full MNAS in NOWS morphine and buprenorphine treatment algorithms. RESULT: Clinical decision rules based on sMNAS-9 yielded sensitivities of 88% or higher and specificities of 85% or higher for predicting the respective rules based on full MNAS. CONCLUSION: The sMNAS-9 scoring instrument is expected to yield similar clinical decisions in treatment of NOWS.
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Algoritmos , Buprenorfina , Morfina , Síndrome de Abstinência Neonatal , Humanos , Síndrome de Abstinência Neonatal/tratamento farmacológico , Síndrome de Abstinência Neonatal/diagnóstico , Recém-Nascido , Estudos Retrospectivos , Feminino , Morfina/uso terapêutico , Buprenorfina/uso terapêutico , Masculino , Analgésicos Opioides/uso terapêutico , Índice de Gravidade de Doença , Regras de Decisão Clínica , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Sensibilidade e EspecificidadeRESUMO
Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta [SNC] and Ventral Tegmental Area [VTA]) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Compelling evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain bulbar DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings in ex vivo brain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential (AP) firing across midbrain and forebrain bulbar DA subtypes. We found that each DA subgroup within midbrain and OB was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single "dopaminergic" neuronal phenotype.
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Neurônios Dopaminérgicos , Proteína Vermelha Fluorescente , Substância Negra , Camundongos , Ratos , Animais , Neurônios Dopaminérgicos/metabolismo , Substância Negra/metabolismo , Bulbo Olfatório , Mesencéfalo/metabolismo , Área Tegmentar Ventral/metabolismoRESUMO
BACKGROUND: Health and wellbeing can be profoundly impacted by both obesity and type 2 diabetes, while the normalisation and equity of care for people living with these non-communicable diseases remain as challenges for local health systems. The National Health Service Low Calorie Diet programme in England, aims to support people to achieve type 2 diabetes remission, while also reducing health inequalities. We have explored the experiences of health care staff who have made a referral to the LCD programme, while identifying effective and equitable delivery of programme referrals, and their normalisation into routine care. METHODS: Nineteen individual semi-structured interviews were completed health care staff in the first year of the Low Calorie Diet programme. Interviewees were purposively sampled from the ten localities who undertook the Low Calorie Diet programme pilot. Each interview explored a number of topics of interest including communication and training, referrals, equity, and demands on primary care, before being subjected to a thematic analysis. RESULTS: From the data, five core themes were identified: Covid-19 and the demands on primary care, the expertise and knowledge of referrers, patient identification and the referral process, barriers to referrals and who gets referred to the NHS LCD programme. Our findings demonstrate the variation in the real world settings of a national diabetes programme. It highlights the challenge of COVID-19 for health care staff, whereby the increased workload of referrals occurred at a time when capacity was curtailed. We have also identified several barriers to referral and have shown that referrals had not yet been normalised into routine care at the point of data collection. We also raise issues of equity in the referral process, as not all eligible people are informed about the programme. CONCLUSIONS: Referral generation had not yet been consistently normalised into routine care, yet our findings suggest that the LCD programme runs the risk of normalising an inequitable referral process. Inequalities remain a significant challenge, and the adoption of an equitable referral process, normalised at a service delivery level, has the capacity to contribute to the improvement of health inequalities.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Restrição Calórica , Diabetes Mellitus Tipo 2/terapia , Medicina Estatal , Encaminhamento e ConsultaRESUMO
BACKGROUND: The National Health Service Type 2 Diabetes Path to Remission programme in England (known as the NHS Low Calorie Diet programme when piloted) was established to support people living with excess weight and Type 2 Diabetes to lose weight and improve their glycaemic control. A mixed method evaluation was commissioned to provide an enhanced understanding of the long-term cost effectiveness of the pilot programme, its implementation, equity and transferability across broad and diverse populations. This study provided key insights on implementation and equity from the service providers' perspective. METHODS: Thirteen focus groups were conducted with commercial providers of the programme, during the initial pilot rollout. Participants were purposively sampled across all provider organisations and staff roles involved in implementing and delivering the programme. Normalisation Process Theory (NPT) was used to design the topic schedule, with the addition of topics on equity and person-centredness. Data were thematically analysed using NPT constructs with additional inductively created codes. Codes were summarised, and analytical themes generated. RESULTS: The programme was found to fulfil the requirements for normalisation from the providers' perspective. However, barriers were identified in engaging GP practices and receiving sufficient referrals, as well as supporting service users through challenges to remain compliant. There was variation in communication and training between provider sites. Areas for learning and improvement included adapting systems and processes and closing the gap where needs of service users are not fully met. CONCLUSIONS: The evaluation of the pilot programme demonstrated that it was workable when supported by effective primary care engagement, comprehensive training, and effective internal and external communication. However, limitations were identified in relation to programme specifications e.g. eligibility criteria, service specification and local commissioning decisions e.g. pattern of roll out, incentivisation of general practice. A person-centred approach to care is fundamental and should include cultural adaptation(s), and the assessment and signposting to additional support and services where required.
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Restrição Calórica , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Medicina Estatal , Comunicação , Definição da ElegibilidadeRESUMO
OBJECTIVE: Evidence suggests that people with severe mental illness (PwSMI) are 2.1 times more likely to die from cancer before the age of 75, compared to people without Severe mental illness (SMI). Yet, cancer screening uptake is low among PwSMI. This mixed-methods systematic review aimed to identify the barriers and facilitators for PwSMI deciding to access and attend primary cancer screening of the cervix, breast and colon. METHODS: Six electronic databases and two grey literature sources were searched, with 1017 records screened against inclusion criteria. Included papers were appraised and data synthesised using the constructs of Normalisation Process Theory. RESULTS: Twenty papers met the inclusion criteria. Factors that impact upon uptake of PwSMI accessing cancer screening were found to include age, gender, race, and income. Common barriers to attending screening included poor communication from healthcare staff, stigmatising attitudes, and accessibility problems such as no access to transportation. While, facilitators included social support from friends, family, and healthcare providers. CONCLUSIONS: Due to ease and privacy, colorectal screening was found to have fewer barriers when compared to cervical and breast screening. The review identified multiple barriers that can be addressed and targeted to support decision-making for cancer screening among PwSMI. The protocol was registered with PROSPERO (CRD42022331781).
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Transtornos Mentais , Neoplasias , Feminino , Humanos , Detecção Precoce de Câncer , Transtornos Mentais/diagnóstico , Pessoal de Saúde , Apoio Social , Neoplasias/diagnósticoRESUMO
With rising rates of human obesity, this study aimed to determine the relationship between maternal diet-induced obesity, offspring morphometrics, and behavior in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of the HFHS offspring was reduced for the first postnatal week but not thereafter, with HFHS female offspring having higher body weights by weaning due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. The maternal diet did not affect the offspring's locomotor activity or social behavior in either sex. Both the male and female HFHS offspring displayed reduced anxiety-related behaviors, with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in the male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behavior of male and female offspring, with sex-specific differences.
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Adiposidade , Açúcares , Humanos , Feminino , Masculino , Gravidez , Camundongos , Animais , Açúcares/metabolismo , Lactação , Dieta Hiperlipídica/efeitos adversos , Obesidade/etiologia , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Fenômenos Fisiológicos da Nutrição MaternaRESUMO
INTRODUCTION: The burden of non-communicable diseases (NCDs) is increasing rapidly, particularly in low- and middle-income countries (LMIC), accounting for 85% of premature deaths in the region. LMICs have been facing an increasing trend of a double burden of disease (infectious diseases and NCDs) that has led to multiple challenges in prioritising strategies for NCDs control amidst limited resources. Evidence indicates that measures such as the WHO's package of essential non-communicable (PEN) diseases interventions can prevent and control NCDs. However, because of the complexity of such health interventions, there is limited evidence that explains how the intervention works, for whom and in what context. We aim to unpack the causal mechanisms explaining how, why, for whom and in what context PEN prevents and controls NCDs. METHODS AND ANALYSIS: We propose a realist review to understand how, why, for whom and under what circumstances PEN works or does not work. The review process includes five steps applied iteratively throughout the study: clarification of review scope, searching for evidence, appraising and extracting data, synthesising evidence and drawing conclusions, and disseminating the findings. Programme theories will be developed using the realist logic for theory formulation-Retroductive Theorising. The context-mechanism-outcome (CMO) heuristic tool will be used to develop the programme theories. Portions of the reviewed documents describing constructs of context, mechanism and outcomes will be coded inductively and extracted. These extracted constructs will then be linked abductively to formulate CMO configurations. ETHICS AND DISSEMINATION: Formal ethical approval is not required for this review. Study findings will be disseminated through publications in peer-reviewed journals, conference presentations and formal and informal reports.
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Países em Desenvolvimento , Doenças não Transmissíveis , Humanos , Doenças não Transmissíveis/prevenção & controle , Projetos de Pesquisa , Literatura de Revisão como AssuntoRESUMO
BACKGROUND: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy. OBJECTIVE: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis. METHODS: A within-trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost-effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost-effectiveness analysis. Secondary analysis, undertaken as a cost-utility analysis, reports incremental cost per Quality-Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU-9D at 2 years. RESULTS: At 2 years, the adjusted incremental cost was £87.45 (95% CI -54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI -0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI -0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, -£106.89 (95% CI -354.66, 140.88) and the proportion without eczema was -0.0329 (95% CI -0.0659, 0.0002). The 5-year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group. CONCLUSIONS: In line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high-risk children does not appear cost-effective.
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Dermatite Atópica , Eczema , Humanos , Lactente , Análise de Custo-Efetividade , Dermatite Atópica/prevenção & controle , Dermatite Atópica/tratamento farmacológico , Eczema/prevenção & controle , Emolientes/uso terapêutico , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVE: This study aimed to analyze the association between acute kidney injury (AKI) and abnormalities on brain magnetic resonance imaging (MRI) or death in neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: This is a retrospective case-control analysis of 380 neonates born at ≥35 weeks' gestation treated with therapeutic hypothermia for HIE. Death or abnormal brain MRI using the basal ganglia watershed scoring system was compared between neonates with and without AKI. RESULTS: A total of 51 (13.4%) neonates had AKI. Infants with AKI had higher rates of the composite of death or abnormal brain MRI (74.5 vs. 38.3%; p < 0.001). Rate of death (21.6 vs. 5.5%; p < 0.001) and severe abnormalities on MRI or death (43.1 vs. 19.1%; p < 0.001) were also higher in neonates with AKI. CONCLUSION: AKI is strongly associated with abnormalities on brain MRI or death in neonates with HIE. Identification of AKI in this patient population may be helpful in guiding clinical management and predicting potential neurodevelopmental impairment. KEY POINTS: · Neonates with HIE are at increased risk for AKI.. · AKI is associated with hypoxic-ischemic injury on brain MRI or death among neonates with HIE.. · Identification of AKI in infants with HIE may help predict neurodevelopmental impairment..
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Obesity is rising globally and is associated with neurodevelopmental and psychiatric disorders among children, adolescents and young adults. Whether obesity is the cause or the consequence of these disorders remains unclear. To examine the behavioural effects of obesity systematically, locomotion, anxiety and social behaviour were assessed in male and female C57Bl/6J mice using the open field, elevated plus maze and social preference task. First, the effects of age and sex were examined in control mice, before investigating post-weaning consumption of a high fat-high sugar diet commonly consumed in human populations with high rates of obesity. In the open field and elevated plus maze, locomotor activity and anxiety-related behaviours reduced with aging in both sexes, but with different sex-specific profiles. The high fat-high sugar diet reduced food and calorie intake and increased body mass and fat deposition in both sexes. In the open field, both male and female mice on the obesogenic diet showed reduced locomotion; whereas, in the elevated plus maze, only females fed with the obesogenic diet displayed reduced anxiety-related behaviours. Both male and female mice on the obesogenic diet had a significantly higher social preference index than the control group. In conclusion, the findings demonstrate that the behavioural effects of age and diet-induced obesity all depend on the sex of the mouse. This emphasises the importance of considering the age of the animal and including both sexes when assessing behavioural phenotypes arising from dietary manipulations.
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Comportamento Animal , Obesidade , Humanos , Criança , Camundongos , Masculino , Animais , Feminino , Adolescente , Obesidade/etiologia , Obesidade/psicologia , Dieta Hiperlipídica/efeitos adversos , Dieta Hiperlipídica/psicologia , Camundongos Endogâmicos C57BL , Açúcares/farmacologiaRESUMO
OBJECTIVE: To compare the effect of a circulating warm water blanket (WWB) in combination with a heated humidified breathing circuit (HHBC) heated to 45 °C on rectal temperature (RT) in dogs undergoing general anesthesia for elective ovariohysterectomies. ANIMALS: 29 healthy dogs. PROCEDURES: Dogs in the experimental group (n = 8) and dogs in the control group (21) were connected to an HHBC and a conventional rebreathing circuit, respectively. All dogs were placed on a WWB in the operating room (OR). The RT was recorded at baseline, premedication, induction, transfer to OR, every 15 minutes during maintenance of anesthesia, and extubation. Incidence of hypothermia (RT < 37 °C) at extubation was recorded. Data were analyzed using unpaired t tests, the Fisher exact test, and mixed-effect ANOVA. Statistical significance was defined as P < .05. RESULTS: There was no difference in RT during baseline, premedication, induction, and transfer to OR. The overall RT was higher for the HHBC group during anesthesia (P = .005) and at extubation (37.7 ± 0.6 °C) compared with the control group (36.6 ± 1.0 °C; P = .006). The incidence of hypothermia at extubation was 12.5% for the HHBC group and 66.7% for the control group (P = .014). CLINICAL RELEVANCE: The combination of HHBC and WWB can reduce the incidence of postanesthetic hypothermia in dogs. Use of an HHBC should be considered in veterinary patients.
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Temperatura Corporal , Hipotermia , Feminino , Cães , Animais , Hipotermia/prevenção & controle , Hipotermia/veterinária , Temperatura Alta , Anestesia Geral/veterinária , Histerectomia/veterináriaRESUMO
INTRODUCTION: The operating room is an increasingly expensive and limited resource. The aim of this study was to evaluate the efficacy, safety, cost, and parental satisfaction of transitioning minor pediatric urology procedures from an operating room setting to a pediatric sedation unit. METHODS: Minor urological procedures were transitioned from the operating room to the pediatric sedation unit if they could be completed in 20 minutes using minimal instrumentation. Information regarding patient demographics, procedure characteristics, rates of success and complications, and cost were collected from urology procedures performed in the pediatric sedation unit between August 2019 and September 2021. Patient demographics and cost data from the most common urology procedures performed in the pediatric sedation unit were compared to data from historical controls of cases occurring in the operating room. Parent surveys were performed following the completion of procedures in the pediatric sedation unit. RESULTS: A total of 103 patients, ranging from 6-207 months old (mean 72 months), underwent procedures in the pediatric sedation unit. The most common procedures were lysis of adhesions and meatotomy. All procedures were successfully completed with procedural sedation, and no procedure was complicated by serious sedation adverse events. The cost reduction for lysis of adhesions in the pediatric sedation unit was 53.5% compared to the operating room, and meatotomy was 27.9%, leading to approximately $57,000 cost savings per year. Fifty families completed a follow-up satisfaction survey, and 83% of parents were satisfied with the care their family received. CONCLUSIONS: The pediatric sedation unit can provide a successful and cost-efficient alternative to the operating room while preserving safety and high rates of parental satisfaction.
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Anestesia , Pacientes Ambulatoriais , Criança , Humanos , Anestesia/efeitos adversos , Salas Cirúrgicas , Inquéritos e Questionários , Sedação Consciente/efeitos adversosRESUMO
Plant receptor kinases are key transducers of extracellular stimuli, such as the presence of beneficial or pathogenic microbes or secreted signaling molecules. Receptor kinases are regulated by numerous post-translational modifications.1,2,3 Here, using the immune receptor kinases FLS24 and EFR,5 we show that S-acylation at a cysteine conserved in all plant receptor kinases is crucial for function. S-acylation involves the addition of long-chain fatty acids to cysteine residues within proteins, altering their biochemical properties and behavior within the membrane environment.6 We observe S-acylation of FLS2 at C-terminal kinase domain cysteine residues within minutes following the perception of its ligand, flg22, in a BAK1 co-receptor and PUB12/13 ubiquitin ligase-dependent manner. We demonstrate that S-acylation is essential for FLS2-mediated immune signaling and resistance to bacterial infection. Similarly, mutating the corresponding conserved cysteine residue in EFR suppressed elf18-triggered signaling. Analysis of unstimulated and activated FLS2-containing complexes using microscopy, detergents, and native membrane DIBMA nanodiscs indicates that S-acylation stabilizes, and promotes retention of, activated receptor kinase complexes at the plasma membrane to increase signaling efficiency.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Ligantes , Cisteína/metabolismo , Plantas/metabolismo , Membrana Celular/metabolismo , Acilação , Imunidade VegetalRESUMO
OBJECTIVE: To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS). STUDY DESIGN: A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days. RESULTS: Twenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p > 0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p = 0.02). A non-significant trend was noted for the duration of hospitalization. There was no difference in need for phenobarbital or clonidine therapy, or total dose of morphine in the first 15 days of NOWS treatment. CONCLUSIONS: Ondansetron treatment reduced the severity of NOWS symptoms; and there was an indication that it could reduce the length of stay. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01965704.
Assuntos
Analgésicos Opioides , Síndrome de Abstinência Neonatal , Recém-Nascido , Humanos , Analgésicos Opioides/uso terapêutico , Ondansetron/uso terapêutico , Morfina/efeitos adversos , Síndrome de Abstinência Neonatal/tratamento farmacológico , Fenobarbital/uso terapêuticoRESUMO
BACKGROUND: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. METHODS: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy. RESULTS: Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever. CONCLUSIONS: Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever.