Development of the utero-placental circulation in cesarean scar pregnancies: A case-control study

BACKGROUND: Cesarean scar pregnancies (CSP) are at high risk of pregnancy complications including placenta previa with antepartum hemorrhage, placenta accreta spectrum (PAS) and uterine rupture. OBJECTIVE: To evaluate the development of the utero-placental circulation in the first half of pregnancy in ongoing CSP and compare it to pregnancies implanted in the lower uterine segment above a prior cesarean section scar with no evidence of PAS at delivery. MATERIAL AND METHODS: This was a retrospective case-control study conducted in two tertiary referral centers. The study group included 27 women diagnosed with a live caesarean scar pregnancy in the first trimester of pregnancy who elected to conservative management. The control group included 27 women diagnosed with a low-lying/placenta previa at 19-22 weeks of gestation who had a first and an early second trimester ultrasound examinations. In both groups, the first ultrasound examination was carried out at 6-10 weeks to establish pregnancy location, viability and to confirm the gestational age. The utero-placental and intra-placental vasculatures were examined using color Doppler imaging (CDI) and described semi quantitatively using CDI score 1-4. The remaining myometrial thickness (RMT) was recorded in the study group whereas in the controls the ultrasound features of prior cesarean scar were noted including the presence of a niche. Both CSP and controls had also ultrasound examinations at 11-14 and 19-22 weeks of gestation. RESULTS: The mean CDI vascularity score at the 6-10 weeks ultrasound examination was significantly (P <.001) higher in the CSP group than in the controls. The high vascularity scores 3 and 4 were recorded in 20/27 (74%) cases of the CSP group. There was no vascularity score of 4 and only 3/27 (11%) controls had vascularity score of 3. In 15/27 (55.6%) CSPs the RMT was < 2 mm. At the 11-14 weeks ultrasound examination, there was no significant difference between the groups for the number of cases with increased subplacental vascularity but 12 CSPs (44%) presented with one or more placental lacunae whereas there was no case with lacunae in the controls. In the 18 CSP that progressed into the third trimester, ten were diagnosed with placenta previa creta at birth, including 4 creta and 6 increta. At the 19-22 weeks ultrasound examination, eight of the ten PAS presented with subplacental hypervascularity out of which, six showed also placental lacunae. CONCLUSION: The vascular changes in the utero-placental and intervillous circulations in CSPs are due to the loss of the normal uterine structure in the scar area and the development of placental tissue in proximity of large diameter arteries of the outer uterine wall. The intensity of these vascular changes, development of PAS and risk of uterine rupture depend on the RMT of the cesarean scar defect at the start of pregnancy. A better understanding of the pathophysiology of the utero-placental vascular changes associated with CSP should help in identifying those cases that may develop major complications and thus contribute to counselling women about the risks associated with different management strategies

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

A review of friction models in interacting joints for durability design.

This paper presents a comprehensive review of friction modelling to provide an understanding of design for durability within interacting systems. Friction is a complex phenomenon and occurs at the interface of two components in relative motion. Over the last several decades, the effects of friction and its modelling techniques have been of significant interests in terms of industrial applications. There is however a need to develop a unified mathematical model for friction to inform design for durability within the context of varying operational conditions. Classical dynamic mechanisms model for the design of control systems has not incorporated friction phenomena due to non-linearity behaviour. Therefore, the tribological performance concurrently with the joint dynamics of a manipulator joint applied in hazardous environments needs to be fully analysed. Previously the dynamics and impact models used in mechanical joints with clearance have also been examined. The inclusion of reliability and durability during the design phase is very important for manipulators which are deployed in harsh environmental and operational conditions. The revolute joint is susceptible to failures such as in heavy manipulators these revolute joints can be represented by lubricated conformal sliding surfaces. The presence of pollutants such as debris and corrosive constituents has the potential to alter the contacting surfaces, would in turn affect the performance of revolute joints, and puts both reliability and durability of the systems at greater risks of failure. Key literature is identified and a review on the latest developments of the science of friction modelling is presented here. This review is based on a large volume of knowledge. Gaps in the relevant field have been identified to capitalise on for future developments. Therefore, this review will bring significant benefits to researchers, academics and industrial professionals

Moving the Needle Toward Fair Compensation in Pediatric Nephrology

Remuneration issues are a substantial threat to the long-term stability of the pediatric nephrology workforce. It is uncertain whether the pediatric nephrology workforce will meet the growing needs of children with kidney disease without a substantial overhaul of the current reimbursement policies. In contrast to adult nephrology, the majority of pediatric nephrologists practice in an academic setting affiliated with a university and/or children's hospital. The pediatric nephrology service line is crucial to maintaining the financial health and wellness of a comprehensive children's hospital. However, in the current fee-for-service system, the clinical care for children with kidney disease is neither sufficiently valued, nor appropriately compensated. Current compensation models derived from the relative value unit (RVU) system contribute to the structural biases inherent in the current inequitable payment system. The perceived negative financial compensation is a significant driver of waning trainee interest in the field which is one of the least attractive specialties for students, with a significant proportion of training spots going unfilled each year and relatively stagnant growth rate as compared to the other pediatric subspecialties. This article reviews the current state of financial compensation issues plaguing the pediatric nephrology subspecialty. We further outline strategies for pediatric nephrologists, hospital administrators, and policy-makers to improve the landscape of financial reimbursement to pediatric subspecialists. A physician compensation model is proposed which aligns clinical activity with alternate metrics for current non-RVU producing activities that harmonizes hospital and personal mission statements

IPNA clinical practice recommendations on care of pediatric patients with pre-existing kidney disease during seasonal outbreak of COVID-19

The coronavirus disease 2019 (COVID-19) pandemic, instigated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly impacted healthcare infrastructures around the globe. While children are usually asymptomatic or have mild symptoms, children with pre-existing kidney conditions require specialized attention. This pivotal report, championed by the International Pediatric Nephrology Association (IPNA), delivers precise and actionable recommendations tailored for pediatric patients with kidney ailments in this pandemic landscape. Central to our findings are rigorous infection control protocols. These are particularly stringent in high-risk zones, emphasizing telehealth's indispensable role, the significance of curtailing in-person consultations, and the imperative of following rigorous guidelines in regions with heightened COVID-19 prevalence. Additionally, the report delves into vaccination approaches for children with kidney issues, highlighting that the choice of vaccine is often governed by regional accessibility and policy frameworks, rather than a universal preference. A notable observation is the potential correlation between COVID-19 vaccines and specific kidney disorders. However, establishing a direct causal link remains elusive. In summary, our research accentuates the critical need for specialized pediatric kidney care during global health crises and reaffirms the continuous research imperative, especially regarding vaccination ramifications

Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe atopic dermatitis in children and young people (TREAT): a multicentre parallel group assessor-blinded clinical trial

Background: Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings. Objectives: To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial. Methods: We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2–16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg–1 daily) or MTX (0.4 mg kg–1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status. Results: In total, 103 participants were randomized (May 2016–February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD –5.69, 97.5% confidence interval (CI) –10.81 to –0.57 (P=0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23–5.49; P=0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13–0.85; P=0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42–6.01; P=0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE. Conclusions: Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation

Exposure–response of ciclosporin and methotrexate in children and young people with severe atopic dermatitis: A secondary analysis of the TREatment of severe Atopic dermatitis Trial (TREAT)

This is a secondary analysis of a multicentre randomised controlled trial of ciclosporin and methotrexate in children and young people (CYP) with severe atopic dermatitis (AD). Longitudinal trough ciclosporin and erythrocyte methotrexate polyglutamates (MTX-PG) concentrations were measured to evaluate their associations with treatment response and adverse events. Both ciclosporin (4 mg/kg/day) and methotrexate (0.4 mg/kg/week) led to a significant reduction in disease severity scores over the 36-week treatment period. Higher trough ciclosporin concentrations were associated with lower disease severity scores and may serve as a useful tool for therapeutic drug monitoring of ciclosporin in CYP with AD. However, in contrast to a previously published study, steady-state erythrocyte-MTX-PG concentrations showed no significant association with treatment response. Drug concentrations were comparable between patients with and without drug-related adverse events

Comparative efficacy of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis

BACKGROUND: Serotonin (5-HT(3)) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients. We conducted a systematic review on the comparative efficacy of 5-HT(3) receptor antagonists. METHODS: Searches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT(3) receptor antagonists with each other, placebo, and/or combined with other antiemetic agents for patients undergoing surgical procedures. Screening search results, data abstraction, and risk of bias assessment were conducted by two reviewers independently. Random-effects pairwise meta-analysis and network meta-analysis (NMA) were conducted. PROSPERO registry number: CRD42013003564. RESULTS: Overall, 450 studies and 80,410 patients were included after the screening of 7,608 citations and 1,014 full-text articles. Significantly fewer patients experienced nausea with any drug relative to placebo, except for ondansetron plus metoclopramide in a NMA including 195 RCTs and 24,230 patients. Significantly fewer patients experienced vomiting with any drug relative to placebo except for palonosetron plus dexamethasone in NMA including 238 RCTs and 12,781 patients. All agents resulted in significantly fewer patients with postoperative nausea and vomiting versus placebo in a NMA including 125 RCTs and 16,667 patients. CONCLUSIONS: Granisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0371-y) contains supplementary material, which is available to authorized users