Comparison of Nicolaides’ risk evaluation for down’s syndrome with a novel software: an analysis of 1,463 cases

Objective The individual risk assessment of fetal Down’s syndrome based on measurement of nuchal translucency (NT) according to Nicolaides, optionally complemented by the determination of PAPP-A and free beta HCG has progressively supplanted other search strategies for fetal aneuploidies. It could be shown that this diagnostic strategy equally detects other numeric aneuploidies at a comparable rate. A positive test result is also predictive for the presence of a fetal malformation. In this field, several computer programs are available for clinical use. The objective of our study was to re-evaluate the first consecutive 1463 NT-risk calculations determined by Nicolaides’ method and to compare the risk calculation to the JOY software (NT-risk calculation module, JOY Patient Database) introduced in 2002. Material and methods At the Department of Obstetrics and Gynecology, Hannover Medical School, 1463 consecutive complete data sets comprising first trimester screening performed between May 2, 2000 and June 26, 2003 and corresponding fetal outcome were analysed using risk assessment based on the Nicolaides method (PIA Fetal Database NT-Module) and compared with the risk evaluation as determined by the JOY software (JOY Patient Database NT module). A risk exceeding 1:300 was considered to indicate the need for further invasive testing. In a first step, only cytogenetically detectable chromosomal aberrations were analysed. Then, a second evaluation including fetal malformations was performed. Results Among the 1463 cases, 1445 (98.77%) fetuses revealed to be cytogenetically healthy. Both softwares showed identical detection rates at the genetic and somatic level:13 cases of Down-Syndrome (0.89%), 2 cases of trisomy 18 (0.14%), one case of triploidy, one Turner-Syndrome, one Klinefelter-Syndrome (0.07% each) were detected. A positive test result was found in 15 cases ending in a spontaneous abortion, intrauterine death or peripartum death (1.03%) and in 22 cases of fetal malformation (1.50%). At the level of genetic detection the test positive rate dropped from 92 (PIA) to 71 (JOY) (-22.8%). At the level of combined adverse outcome the test positive rate was reduced from 100 (PIA) to 76 (JOY) (-22.0%), thus yielding in a marked improvement of the characteristic test performance parameters. Conclusion The novel, recently developed JOY software package allowed reliable evaluation of the risk for aneuploidy with increased specificity whereas sensitivity was unchanged. Our data suggest an improvement of the screening for aneuploidy when using this novel software: With an identical detection rate, the number of unnecessary invasive measures may be reduced.     

The significance of intracardiac Doppler sonography in terms of fetal growth retardation

Introduction

The proper function of the fetal heart is indispensable for the fetal development and the normal fetal growth. For prenatal medicine, Doppler sonography offers the possibility of a non-invasive method to examine the fetal cardiovascular function under normal and pathological circumstances. The role of the Doppler sonography is to identify those fetuses who have a high risk factor for developing a pre- or intrapartual asphyxia and therefore have to be delivered promptly. This study aimed at evaluating the clinical value of the intracardiac Doppler sonography (IDS) and at scrutinizing its usefulness during the supervision of the pregnancy of intrauterine growth restricted (IUGR) fetuses.

Materials and methods

In a prospective research at the Medical School of Hanover, fetal IDS was applied to 174 pregnant women between the 21 and 37 weeks of gestation (WG). The e-wave and the a-wave, the E/A ratio, and the TVI (time velocity integral) were measured at the atrioventricular (AV) valves. The PV (peak velocity) as well as the TVI were determined at both the aortic and the pulmonary valve. Normal range curves were compiled for all measured parameters.

Results

Alongside a control group with untroubled gravidity, which consisted of 153 patients, IUGR fetuses, who formed a collective of 21 patients, were Doppler sonographically examined.While the gestational age advanced, an increase of both the e-wave and the a-wave above the AV-valves could be ascertained, which lead to an E/A ratio <1. Above the semilunar valves there was indicated a slight steady increase of the TPV, the PV as well as the TVI. Normal range curves, which largely correspond to those described in the literature, were compiled for the collective of the pregnancies without pathological findings (n = 153). In comparison to the standard collective, there were no significant differences from the collective of the growth restricted fetuses (n = 21).

Conclusion

A temporal informational advantage of pathological intracardiac Doppler values for high risk pregnancies (IUGR) could not be retraced in the examined collective.Doppler sonography traces acute and chronic deficits, which are indicated by hemodynamic changes of the fetus’s blood supply. The clinical importance of IDS as regards dystrophic fetuses has to be ascertained in continuative studies: In the stage of compensatory placental insufficiency (IUGR, arterial Doppler without ARED-flow, venous Doppler without pathological findings) the IDS cannot provide an informational advantage. Contrastingly, the diagnostic potential of the IDS as a screening method of fetal cardiac insufficiency during decompensative placental insufficiency (IUGR, arterial Doppler with ARED-flow, venous Doppler normal or pathological) remains indistinct and should therefore be prospectively evaluated within this high risk group and contrastingly compared to the significance of the venous Doppler sonography (informational advantage?).

     

Strahlenwirkungen

Ohne Zusammenfassung     

Hormone

Ohne Zusammenfassung     

Buchbesprechungen

Ohne Zusammenfassung     

Refeeding Syndrome: A Critical Reality in Patients with Chronic Disease

Malnutrition is one of the most frequent metabolic challenges in the population of chronically ill patients. This results in increased administration of nutritional therapy in inpatient settings, which poses the risk of side effects, in particular, the development of refeeding syndrome. If not managed accordingly, it leads to a significant rise in morbidity and mortality. However, despite its importance, evidence-based recommendations on the management of refeeding syndrome are largely lacking, and only a few randomized controlled trials have been conducted. In light of this, the aim of this review is to raise awareness of refeeding syndrome in chronically ill patients by critically reviewing recent literature and providing a short overview as well as diagnosis and treatment algorithms of this underreported metabolic condition. In summary, recent findings suggest undergoing risk assessment and stratification for every patient receiving nutritional therapy. According to this, adaptation of energy and fluid support during the replenishment phase should be implemented in the nutritional therapy for patients at high risk. Additionally, continuous monitoring should take place, and appropriate actions should be initiated when necessary.     

Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.     

Costs of seasonal influenza vaccination in South Africa

BackgroundInfluenza accounts for a substantial number of deaths and hospitalisations annually in South Africa. To address this disease burden, the South African National Department of Health introduced a trivalent inactivated influenza vaccination programme in 2010.MethodsWe adapted and populated the WHO Seasonal Influenza Immunization Costing Tool (WHO SIICT) with country‐specific data to estimate the cost of the influenza vaccination programme in South Africa. Data were obtained through key‐informant interviews at different levels of the health system and through a review of existing secondary data sources. Costs were estimated from a public provider perspective and expressed in 2018 prices. We conducted scenario analyses to assess the impact of different levels of programme expansion and the use of quadrivalent vaccines on total programme costs.ResultsTotal financial and economic costs were estimated at approximately USD 2.93 million and USD 7.91 million, respectively, while financial and economic cost per person immunised was estimated at USD 3.29 and USD 8.88, respectively. Expanding the programme by 5% and 10% increased economic cost per person immunised to USD 9.36 and USD 9.52 in the two scenarios, respectively. Finally, replacing trivalent inactivated influenza vaccine (TIV) with quadrivalent vaccine increased financial and economic costs to USD 4.89 and USD 10.48 per person immunised, respectively.ConclusionWe adapted the WHO SIICT and provide estimates of the total costs of the seasonal influenza vaccination programme in South Africa. These estimates provide a basis for planning future programme expansion and may serve as inputs for cost‐effectiveness analyses of seasonal influenza vaccination programmes.