Discontinuing absorbent pants in children with bedwetting: a randomized controlled trial.

The objective of this study is to examine the effect of discontinuing wearing protective garments (absorbent pyjama pants - APP) in children with severe childhood nocturnal enuresis (NE). The study employs a multicenter, parallel, randomized controlled trial. Following a 4-week run-in period, participants were randomly allocated in a 2:1 group allocation to discontinue or continue using APP. The research was conducted across seven European pediatric incontinence centers. The study included treatment-naïve children aged 4-8 years with severe (7/7 wet nights per week) mono-symptomatic NE, who had used nighttime protection for at least 6 months prior to the study. The study consisted of a 4-week run-in period (± 7 days), where all children slept wearing APP (DryNites®). At week 4 (± 7 days), if meeting randomization criteria (7/7 wet nights during the last week of run-in), participants were randomized to continue to sleep in APP or to discontinue their use for a further 4 weeks, with the option of another 4 weeks in the extension period. The primary outcome was the difference between groups of wet nights during the last week of intervention. Quality of life (QoL) and sleep were secondary endpoints. In total, 105 children (43 girls and 62 boys, mean age 5.6 years [SD 1.13]) were randomized (no-pants group n = 70, pants group n = 35). Fifteen children (21%) in the no-pants group discontinued early due to stress related to the intervention. Children in the no-pants group experienced fewer wet nights compared to the pants group during the last week (difference 2.3 nights, 95% CI 1.54-3.08; p < 0.0001). In the no-pants group, 20% responded to the intervention, of whom 13% had a full response. Clinical improvement was detected within 2 weeks. Sleep and QoL were reported as negatively affected by APP discontinuation in the extension period but not in the core period.    Conclusion: A ~ 10% complete resolution rate was associated with discontinuing APP. While statistically significant, the clinical relevance is debatable, and the intervention should be tried only if the family is motivated. Response was detectable within 2 weeks. Discontinuing APP for 4-8 weeks was reported to negatively affect QoL and sleep quality. No severe side effects were seen.Trial registration: Clinicaltrials.gov Identifier: NCT04620356; date registered: September 23, 2020. Registered under the name: "Effect of Use of DryNites Absorbent Pyjama Pants on the Rate of Spontaneous Resolution of Paediatric Nocturnal Enuresis (NE)."

Use of methadone as an alternative to morphine for chronic pain management: a noninferiority retrospective observational study.

INTRODUCTION: Chronic pain causes disability and is prevalent in the general population. Opioids are a part of a multimodal strategy for pain management. Methadone, a cheap and long-acting synthetic opioid, may represent an option for those who have limited access to the aforementioned class of analgesics. We aimed to provide a real-world evidence for the analgesic use of methadone, compared with morphine. METHODS: We conducted a noninferiority, retrospective observational single center study of patients with chronic pain, managed with either methadone or morphine at an outpatient specialized clinic. We extracted data from the electronic health records of patients who underwent an active treatment between August 2012 and January 2020 and were examined for at least 2 consecutive medical visits, after the administration of one of the aforementioned drugs. Data were analyzed using a generalized additive model with random-effects mixed linear method to account for the individual-related, time-related, and drug-related variations. The numeric verbal scale (0-10) was used to assess the pain severity. RESULTS: From the database of 3373 patients, we included 262 patients (175 methadone and 87 morphine). In an unadjusted analysis, methadone was superior to morphine, and the mean worst pain was 0.86 points lower (95% confidence interval, -1.29 to -0.43). Moreover, methadone was superior to morphine in the adjusted analysis, with the worst pain mean being 1.24 points lower. This provided evidence for the noninferiority of methadone than morphine. CONCLUSION: Methadone was superior to morphine in a 20% noninferiority margin for reducing worst pain.

Efficacy and Safety of a Biosimilar Versus Branded Enoxaparin in the Prevention of Venous Thromboembolism Following Major Abdominal Surgery: A Randomized, Prospective, Single-Blinded, Multicenter Clinical Trial.

Several biosimilar versions of enoxaparin are already approved and in use globally. Analytical characterization can establish good quality control in manufacturing, but they may not assure similarity in clinical outcomes between biosimilar and branded enoxaparin. This study evaluated the efficacy and safety of biosimilar Cristália versus branded Sanofi enoxaparin in venous thromboembolism (VTE) prevention in patients undergoing major abdominal surgery at risk for VTE. In this randomized, prospective single-blind study, we compared Cristália enoxaparin (Ce), a biosimilar version, versus branded Sanofi enoxaparin (Se; at a dose of 40 mg subcutaneously per day postoperatively from 7 to 10 days) in 243 patients submitted to major abdominal surgery at risk for VTE for VTE prevention. The primary efficacy outcome was occurrence of VTE or death related to VTE. The principal safety outcomes were a combination of major bleeding and clinically relevant non-major bleeding. Bilateral duplex scanning of the legs was performed from days 10 to 14, and follow-ups were performed up to 60 days after surgery. The incidence of VTE was 4.9% in the Cristália group and 1.1% in the Sanofi group (absolute risk difference = 3.80%, 95% confidence interval [CI]: -1.4%-9.0%) yielding noninferiority since the 95% CI does not reach the prespecified value Δ = 20%. Clinically significant bleeding occurred in 9.9% in the Cristália group and in 5.5% in the Sanofi group (n.s. ). In conclusion, this study suggests that 40 mg once daily of Ce, a biosimilar enoxaparin, is as effective and safe as the branded Sanofi enoxaparin in the prophylaxis of VTE in patients submitted to major abdominal surgery at risk for VTE.

Uptake of high density lipoprotein (HDL) cholesteryl esters by human acute leukemia cells.

Hypocholesterolemia is a common finding in patients with acute leukemia (AL). The aim of this study is to investigate if blast myeloid and lynfoid cells take up more high density lipoprotein (HDL) cholesteryl esters than normal cells of the same origin. The HDL-cholesteryl ester uptake followed a kinetic saturation process. Higher maximal velocity rates were found in lymphoblasts and myeloblasts compared to normal cells (Vmax=3.51+/-0.30/3.61+/-0.16 and 2.54+/-0.12/2.28+/-0.12 microg/mg, respectively). High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol were significantly lower in AL patients (p<0.05); no differences were observed in triglyceride or VLDL-C levels. In conclusion, low HDL-C levels observed in AL may be related to an overexpression of a selective HDL-cholesteryl ester putative site.

Associação do quimioterápico paclitaxel a uma microemulsão rica em colesterol (LDE): estudos de toxicidade, biodistribuição e atividade terapêutica em modelo animal / Association of the paclitaxel to a cholesterol-rich microemulsion (LDE): toxicity, biodistribution and therapeutic activity studies in animal model

Depois de ser injetada na circulação, a microemulsão rica em colesterol (LDE) é captada pelos receptores da lipoproteína de baixa densidade (LDL), os quais são super expressados em algumas células neoplásicas. Portanto, a LDE pode ser utilizada como veículo no direcionamento de agentes quimioterápicos para tecidos neoplásicos. O paclitaxel, uma droga de ação anti-neoplásica conhecida, é utilizado em câncer avançado de ovário e mama. Além dos efeitos colaterais causados pelo fármaco, o veículo usado para a sua solubilização, é responsável por importantes reações de hipersensibilidade. Neste estudo, a adição do grupo oleíla a molécula de paclitaxel foi proposta com a finalidade de se aumentar a lipofilicidade do fármaco e permitir uma associação estável com a LDE...