Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Children with HeFH exhibit early signs of atherosclerosis manifested by ...increased carotid intima-media thickness (IMT). In this study, we assessed the effect of 2-year treatment with rosuvastatin on carotid IMT in children with HeFH.
Children with HeFH (age, 6-<18 years) and low-density lipoprotein cholesterol >4.9 mmol/L or >4.1 mmol/L in combination with other risk factors received rosuvastatin for 2 years, starting at 5 mg once daily, with uptitration to 10 mg (age, 6-<10 years) or 20 mg (age, 10-<18 years). Carotid IMT was assessed by ultrasonography at baseline and 12 and 24 months in all patients and in age-matched unaffected siblings. Carotid IMT was measured at 3 locations (common carotid artery, carotid bulb, internal carotid artery) in both the left and right carotid arteries. A linear mixed-effects model was used to evaluate differences in carotid IMT between children with HeFH and the unaffected siblings.
values were adjusted for age, sex, carotid artery site, and family relations.
At baseline, mean±SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397±0.049 and 0.377±0.045 mm, respectively;
=0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm/y (95% confidence interval, 0.0030-0.0082) in children with HeFH and 0.0143 mm/y (95% confidence interval, 0.0095-0.0192) in unaffected siblings (
=0.002). The end-of-study difference in mean carotid IMT between children with HeFH and unaffected siblings after 2 years was no longer significant (0.408±0.043 and 0.402±0.042 mm, respectively;
=0.2).
In children with HeFH who were ≥6 years of age, carotid IMT was significantly greater at baseline compared with unaffected siblings. Rosuvastatin treatment for 2 years resulted in significantly less progression of increased carotid IMT in children with HeFH than untreated unaffected siblings. As a result, no difference in carotid IMT could be detected between the 2 groups after 2 years of rosuvastatin. These findings support the value of early initiation of statin treatment for low-density lipoprotein cholesterol reduction in children with HeFH.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01078675.
In contemporary practice many nulliparous women require intervention during childbirth such as operative vaginal delivery or cesarean delivery (CD). Despite the knowledge that the increasing rate of ...CD is associated with increasing maternal age, obesity and larger infant birthweight, we lack a reliable method to predict the requirement for such potentially hazardous obstetric procedures during labor and delivery. This issue is important, as there are greater rates of morbidity and mortality associated with unplanned CD performed in labor compared with scheduled CDs. A prediction algorithm to identify women at risk of an unplanned CD could help reduced labor associated morbidity.
In this primary analysis of the Genesis study, our objective was to prospectively assess the use of prenatally determined, maternal and fetal, anthropomorphic, clinical, and ultrasound features to develop a predictive tool for unplanned CD in the term nulliparous woman, before the onset of labor.
The Genesis study recruited 2336 nulliparous women with a vertex presentation between 39+0 and 40+6 weeks’ gestation in a prospective multicenter national study to examine predictors of CD. At recruitment, a detailed clinical evaluation and ultrasound assessment were performed. To reduce bias from knowledge of these data potentially influencing mode of delivery, women, midwives, and obstetricians were blinded to the ultrasound data. All hypothetical prenatal risk factors for unplanned CD were assessed as a composite. Multiple logistic regression analysis and mathematical modeling was used to develop a risk evaluation tool for CD in nulliparous women. Continuous predictors were standardized using z scores.
From a total enrolled cohort of 2336 nulliparous participants, 491 (21%) had an unplanned CD. Five parameters were determined to be the best combined predictors of CD. These were advancing maternal age (odds ratio OR, 1.21; 95% confidence interval CI, 1.09 to 1.34), shorter maternal height (OR, 1.72; 95% CI, 1.52 to 1.93), increasing body mass index (OR, 1.29; 95% CI, 1.17 to 1.43), larger fetal abdominal circumference (OR, 1.23; 95% CI, 1.1 to 1.38), and larger fetal head circumference (OR, 1.27; 95% CI, 1.14 to 1.42). A nomogram was developed to provide an individualized risk assessment to predict CD in clinical practice, with excellent calibration and discriminative ability (Kolmogorov–Smirnov, D statistic, 0.29; 95% CI, 0.28 to 0.30) with a misclassification rate of 0.21 (95% CI, 0.19 to 0.25).
Five parameters (maternal age, body mass index, height, fetal abdominal circumference, and fetal head circumference) can, in combination, be used to better determine the overall risk of CD in nulliparous women at term. A risk score can be used to inform women of their individualized probability of CD. This risk tool may be useful for reassuring most women regarding their likely success at achieving an uncomplicated vaginal delivery as well as selecting those patients with such a high risk for CD that they should avoid a trial of labor. Such a risk tool has the potential to greatly improve planning hospital service needs and minimizing patient risk.
Abstract Objectives: To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure. Design: Randomised controlled trial. Setting: Acute medical admissions ...unit in a teaching hospital. Participants: 165 patients admitted with heart failure due to left ventricular systolic dysfunction. The intervention started before discharge and continued thereafter with home visits for up to 1 year. Main outcome measures: Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure. Results: 31 patients (37%) in the intervention group died or were readmitted with heart failure compared with 45 (53%) in the usual care group (hazard ratio=0.61, 95% confidence interval 0.33 to 0.96).Compared with usual care, patients in the intervention group had fewer readmissions for any reason (86 v 114, P=0.018), fewer admissions for heart failure (19 v 45, P<0.001) and spent fewer days in hospital for heart failure (mean 3.43 v 7.46 days, P=0.0051). Conclusions: Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure. What is already known on this topic Studies have suggested that nurse intervention may reduce readmission in patients with heart failure What this study adds Home based intervention from nurses reduces readmissions for worsening heart failure Regular contact to review treatment and patient education are likely to contribute to this effect
Vaginal birth after caesarean (VBAC) delivery remains a controversial topic, and one for which there is a lack of robust data to guide clinicians and parturients regarding their best option for mode ...of delivery in a subsequent pregnancy. In many developed countries the trend observed in recent years is that of progressively reduced VBAC rates, and hence increased use of elective repeat caesarean section (ERCS). This factor has contributed, more than any other, to the disproportionately high caesarean section (CS) rates in many countries. With current CS rates varying between 30 and 50% in the developed world, a previous CS is the cited primary indication in approximately 30%. To compound matters, there are huge variations in the reported VBAC rates between different countries, regions and even institutions. This review has focused on the recent trends in VBAC attempt, success and overall rates internationally, with inclusion of figures for a period of 25 years from a single Irish institution. An analysis of the reported factors that influence VBAC success, or failure, is presented. The complex task of estimating risk, both perinatal and maternal, for women who pursue VBAC or ERCS, is included in this review. Finally, the current evidence base for clinical practice pertaining to VBAC is outlined, with inclusion of commentary regarding the future for this difficult area of obstetric practice.
The Active Healthy Kids Global Alliance organized the concurrent preparation of Report Cards on the physical activity of children and youth in 38 countries from 6 continents (representing 60% of the ...world's population). Nine common indicators were used (Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behavior, Family and Peers, School, Community and the Built Environment, and Government Strategies and Investments), and all Report Cards were generated through a harmonized development process and a standardized grading framework (from A = excellent, to F = failing). The 38 Report Cards were presented at the International Congress on Physical Activity and Public Health in Bangkok, Thailand on November 16, 2016. The consolidated findings are summarized in the form of a Global Matrix demonstrating substantial variation in grades both within and across countries. Countries that lead in certain indicators often lag in others. Average grades for both Overall Physical Activity and Sedentary Behavior around the world are D (low/poor). In contrast, the average grade for indicators related to supports for physical activity was C. Lower-income countries generally had better grades on Overall Physical Activity, Active Transportation, and Sedentary Behaviors compared with higher-income countries, yet worse grades for supports from Family and Peers, Community and the Built Environment, and Government Strategies and Investments. Average grades for all indicators combined were highest (best) in Denmark, Slovenia, and the Netherlands. Many surveillance and research gaps were apparent, especially for the Active Play and Family and Peers indicators. International cooperation and cross-fertilization is encouraged to address existing challenges, understand underlying determinants, conceive innovative solutions, and mitigate the global childhood inactivity crisis. The paradox of higher physical activity and lower sedentary behavior in countries reporting poorer infrastructure, and lower physical activity and higher sedentary behavior in countries reporting better infrastructure, suggests that autonomy to play, travel, or chore requirements and/or fewer attractive sedentary pursuits, rather than infrastructure and structured activities, may facilitate higher levels of physical activity.
The synthesis of (
)-phenylazo-3-
-(4-hydroxyphenyl)maleimide (
) using a procedure previously reported in
is deemed to be erroneous. A detailed re-investigation of the earlier work suggests that the ...spectral data for key intermediates and the final product, (
), was mis-assigned. We conclude that compound (
) was not synthesized, but rather an unusual ring opening reaction of the maleimide unit of the starting material,
-(4-hydroxyphenyl)maleimide (
) leading to the generation of (
)-4-((4-hydroxyphenyl)amino)-4-oxobut-2-enoic acid, (
) was observed instead. Examination of the original experimental data reveals systematic errors in the reporting of all of the combustion microanalytical data. Overall, the present investigation suggests that errors in the interpretation of spectral data, falsification of analytical data and selective editing of experimental results raise questions over the veracity of the work presented in the original paper.
Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics ...associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. This was a retrospective observational cohort study conducted at a five hospital health system in Michigan, United States. Adult patients with confirmed COVID-19 that were admitted to the hospital and received tocilizumab for cytokine storm from March 1, 2020 through April 3, 2020 were included. Patients were grouped into survivors and non-survivors based on 28 day in-hospital mortality. Study day 0 was defined as the day tocilizumab was administered. Factors independently associated with in-hospital survival at 28 days after tocilizumab administration were assessed. Epidemiologic, demographic, laboratory, prognostic scores, treatment, and outcome data were collected and analyzed. Clinical response was collected and defined as a decline of two levels on a six-point ordinal scale of clinical status or discharged alive from the hospital. Of the 81 patients included, the median age was 64 (58–71) years and 56 (69.1%) were male. The 28 day in-hospital mortality was 43.2%. There were 46 (56.8%) patients in the survivors and 35 (43.2%) in the non-survivors group. On study day 0 no differences were noted in demographics, clinical characteristics, severity of illness scores, or treatments received between survivors and non-survivors. C-reactive protein was significantly higher in the non-survivors compared to survivors. Compared to non-survivors, recipients of tocilizumab within 12 days of symptom onset was independently associated with survival (adjusted OR: 0.296, 95% CI: 0.098–0.889). SOFA score ≥8 on day 0 was independently associated with mortality (adjusted OR: 2.842, 95% CI: 1.042–7.753). Clinical response occurred more commonly in survivors than non-survivors (80.4% vs. 5.7%; p < 0.001). Improvements in the six-point ordinal scale and SOFA score were observed in survivors after tocilizumab. Early receipt of tocilizumab in patients with severe COVID-19 was an independent predictor for in-hospital survival at 28 days.
•Patients receiving tocilizumab within 12 days of COVID-19 symptom onset had an increase in 28 day in-hospital survival.•A higher severity of illness prior to tocilizumab administration was associated with increased mortality.•Secondary infections occurred in 22.2% receiving tocilizumab, but infection was not associated with increased mortality.
Objective Obesity is an increasing problem in obstetric practice. Apelin, secreted by adipocytes, is present in increased serum concentrations in an obese state. Our group has previously highlighted ...that the adipokines leptin and ghrelin have a potential role in metabolic modulation of uterine contractility in obese women. The aim of this study was to evaluate the effects of apelin on human uterine contractility in vitro. Study Design Biopsies of human myometrium were obtained at elective cesarean section. Myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of apelin in the concentration range of 1 nmol/L to 1 μmol/L. Control experiments were performed simultaneously. Results Apelin exerted an inhibitory effect on spontaneous and oxytocin induced contractions in human myometrium. The mean maximal inhibition values were 36.8 ± 6.4% for spontaneous (n = 6; P = .002) and 30.4 ± 4.6% for oxytocin-induced contractions (n = 6; P < .0001). Conclusion Apelin inhibits human uterine contractility in vitro, raising the possibility that such metabolic modulation may play a physiological role in obese parturients.
IntroductionLyme disease is the most common vectorborne disease in the Northern hemisphere with more than 400 000 new cases in the USA annually. Lyme meningitis is an uncommon but potentially serious ...clinical manifestation of Lyme disease. Intravenous ceftriaxone had been the first-line treatment for Lyme meningitis, but is associated with a high rate of complications. Although efficacy and effectiveness (or real-world evidence) data for oral doxycycline are limited, practice guidelines were recently expanded to recommend either oral doxycycline or ceftriaxone as first-line treatments for Lyme meningitis. Our goal is to compare oral doxycycline with intravenous ceftriaxone for the treatment of Lyme meningitis on short-term recovery and long-term quality of life.Methods and analysisWe are performing a prospective cohort study at 20 US paediatric centres located in diverse geographical range where Lyme disease is endemic. The clinical care team will make all antibiotic treatment decisions for children with Lyme meningitis, as per usual practice. We will follow enrolled children for 6 months to determine time of acute symptom recovery and impact on quality of life.Ethics and disseminationBoston Children’s Hospital, the single Institutional Review Board (sIRB), has approved the study protocol with the other 19 enrolling sites as well as the Utah data coordinating centre relying on the Boston Children’s Hospital sIRB. Once the study is completed, we will publish our findings in a peer-reviewed medical journal.
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