A network meta-analysis of primary prophylaxis for invasive fungal infection in haematological patients.

WHAT IS KNOWN AND OBJECTIVE: Antifungal prophylaxis is an option to reduce the incidence of invasive fungal infection (IFI) in haematological patients. To date, no network meta-analysis (NMA) of high-quality evidence (double-blind randomized controlled trials) has been performed on this subject. This systematic review and NMA aimed to evaluate the safety and efficacy of different antifungal agents used for prophylaxis of IFI in patients with haematological disorders. METHODS: A systematic review was performed according to PRISMA and Cochrane recommendations. The search for articles was conducted on PubMed, Scopus and the Web of Science. We searched for double-blind randomized clinical trials comparing antifungal agents for IFI prophylaxis head-to-head vs placebo in patients with any blood cancer. Network meta-analyses were conducted using Addis version 1.16.6. Evaluation of the quality of included RCTs was also performed. RESULTS: Twenty-five trials were included in the qualitative and quantitative analyses. Posaconazole stood out as the best IFI prophylaxis option and for avoiding IFI-related mortality. For the incidence of candidiasis outcome, the azoles were superior to placebo. Voriconazole and posaconazole were, respectively, the first and second best options. For the incidence of aspergillosis outcome, the probability rank suggested that voriconazole followed by liposomal amphotericin B is, possibly, the best choice. The quality of studies was considered good, with a mean Jadad score of 4.0. WHAT IS NEW AND CONCLUSION: The results of our work support prophylaxis with antifungal agents as reducing the risk of IFI in haematological patients. Overall, the second-generation azoles were found to be the best option for preventing IFI in this population.

Erratum: Spectroscopic Quadrupole Moments in

This corrects the article DOI: 10.1103/PhysRevLett.116.022701.

Safety of interferon-free therapies for chronic hepatitis C: a network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Interferon-free (IFN-free) therapies for hepatitis C virus (HCV) have been developed to provide more effective, tolerable and safer therapeutic strategies. To date, no network meta-analysis (NMA) evaluating the safety profile of these regimens has been performed. This systematic review and NMA aimed to evaluate safety outcomes of IFN-free treatment options for chronic hepatitis C. METHODS: A systematic review was performed according to PRISMA and Cochrane recommendations. A literature search was conducted in PubMed/Medline, Scopus, Cochrane Library, International Pharmaceutical Abstracts and Web of Science electronic databases and included only randomized clinical trials that provided safety outcomes of interest of evaluated second-generation direct-acting antivirals: incidence of any adverse events (AEs) and serious AE. NMA allowed estimating probability for the relative safety of the interventions. A consistency model was used to draw conclusions about relative safety of treatments, presented as odds ratio (OR) and corresponding 95% credible interval (CrI). RESULTS: Fifty-one clinical trials were included (13 089 participants). Most participants had hepatitis C genotype 1 virus (76%) and were treated for 12 weeks. Two NMAs were built to investigate the incidence of AEs and serious AEs, comparing 13 and 10 IFN-free treatment options, respectively. For the outcome incidence of AEs, few significant differences were observed, which were explained by the presence of RBV. Elbasvir with grazoprevir and placebo were both safer than ombitasvir in combination with paritaprevir, ritonavir, daclatasvir plus RBV [ORs with 95% Crl of 4·09 (1·17-14·09) and 2·40 (1·19-4·77), respectively] and sofosbuvir with RBV [ORs with 95% Crl of 0·22 (0·07-0·72) and 2·69 (1·53-4·80), respectively]. Furthermore, elbasvir with grazoprevir was safer than sofosbuvir used with velpatasvir and RBV [OR 0·19 (95% CrI 0·03-0·98)]; ombitasvir in combination with paritaprevir, ritonavir, daclatasvir was safer than the same therapy but combined with RBV [OR 2·14 (95% CrI 1·09-4·44)]; and sofosbuvir used with velpatasvir was safer than sofosbuvir with RBV [OR 2·07 (95% CrI 1·13-3·79)]. Elbasvir with grazoprevir (50%) followed by placebo (28%) had the highest probabilities of less AEs. No significant differences were observed for serious AE outcomes. WHAT IS NEW AND CONCLUSION: This meta-analysis included a large number of therapies. Small differences were observed in any AEs, but not in serious AEs.

Direct Evidence of Octupole Deformation in Neutron-Rich

The neutron-rich nucleus ^{144}Ba (t_{1/2}=11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV ^{144}Ba beam on a 1.0-mg/cm^{2} ^{208}Pb target. The measured value of the matrix element, ⟨3_{1}^{-}∥M(E3)∥0_{1}^{+}⟩=0.65(+17/-23) eb^{3/2}, corresponds to a reduced B(E3) transition probability of 48(+25/-34) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.

Spectroscopic Quadrupole Moments in {96,98}Sr: Evidence for Shape Coexistence in Neutron-Rich Strontium Isotopes at N=60.

Neutron-rich {96,98}Sr isotopes have been investigated by safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility. Reduced transition probabilities and spectroscopic quadrupole moments have been extracted from the differential Coulomb excitation cross sections. These results allow, for the first time, the drawing of definite conclusions about the shape coexistence of highly deformed prolate and spherical configurations. In particular, a very small mixing between the coexisting states is observed, contrary to other mass regions where strong mixing is present. Experimental results have been compared to beyond-mean-field calculations using the Gogny D1S interaction in a five-dimensional collective Hamiltonian formalism, which reproduce the shape change at N=60.

Decay and Fission Hindrance of Two- and Four-Quasiparticle K Isomers in

Two isomers decaying by electromagnetic transitions with half-lives of 4.7(1.1) and 247(73) µs have been discovered in the heavy ^{254}Rf nucleus. The observation of the shorter-lived isomer was made possible by a novel application of a digital data acquisition system. The isomers were interpreted as the K^{π}=8^{-}, ν^{2}(7/2^{+}[624],9/2^{-}[734]) two-quasineutron and the K^{π}=16^{+}, 8^{-}ν^{2}(7/2^{+}[624],9/2^{-}[734])⊗8^{-}π^{2}(7/2^{-}[514],9/2^{+}[624]) four-quasiparticle configurations, respectively. Surprisingly, the lifetime of the two-quasiparticle isomer is more than 4 orders of magnitude shorter than what has been observed for analogous isomers in the lighter N=150 isotones. The four-quasiparticle isomer is longer lived than the ^{254}Rf ground state that decays exclusively by spontaneous fission with a half-life of 23.2(1.1) µs. The absence of sizable fission branches from either of the isomers implies unprecedented fission hindrance relative to the ground state.

Optimally efficient swimming in hyper-redundant mechanisms: control, design, and energy recovery.

Hyper-redundant mechanisms (HRMs), also known as snake-like robots, are highly adaptable during locomotion on land. Researchers are currently working to extend their capabilities to aquatic environments through biomimetic undulatory propulsion. In addition to increasing the versatility of the system, truly biomimetic swimming could also provide excellent locomotion efficiency. Unfortunately, the complexity of the system precludes the development of a functional solution to achieve this. To explore this problem, a rapid optimization process is used to generate efficient HRM swimming gaits. The low computational cost of the approach allows for multiple optimizations over a broad range of system conditions. By observing how these conditions affect optimal kinematics, a number of new insights are developed regarding undulatory swimming in robotic systems. Two key conditions are varied within the study, swimming speed and energy recovery. It is found that the swimmer mimics the speed control behaviour of natural fish and that energy recovery drastically increases the system's efficiency. Remarkably, this efficiency increase is accompanied by a distinct change in swimming kinematics. With energy recovery, the swimmer converges to a clearly anguilliform gait, without, it tends towards the carangiform mode.

The impact of first trimester screening and early fetal anomaly scan on invasive testing rates in women with advanced maternal age.

PURPOSE: To evaluate the acceptance of noninvasive screening for trisomy 13, 18, 21 and the impact on invasive testing rates in women at an age≥35 years. MATERIALS AND METHODS: In a retrospective analysis from 2003-2006 including 13 268 women≥35 years old with singleton pregnancies and 3133 invasive procedures, we evaluated the prenatal detection rate of aneuploidies in two cohorts. Group 1: advanced maternal age as sole indication, group 2: additional abnormalities and/or suspicious maternal serum parameters. In an additional analysis from 1998-2006 including 31,076 patients≥35 years, we investigated the shift in time of sonography at 11+0-13+6, 14+0-17+6 and 18+0-22+6 gestational weeks (gw). RESULTS: Among 13,268 women, 3133 invasive tests were performed with a significant decrease over time (-17%). 9% of women chose invasive testing after a normal ultrasound (group 1, n=1,267) and 14% in the case of additional markers (group 2, n=1,866). 102 cases of aneuploidy were disclosed. The proportion of detected aneuploidies was 0.86% in group 1 and 4.9% in group 2. No change in the overall detection rate (90-93%) was observed. The number of patients≥40 years increased significantly (+2.8%). There was an increase in examinations at 11+0-13+6 gw (+8%), a decrease at 14+0-17+6 gw (-10.3%) and no significant change at 18+0-22+6 gw over time. CONCLUSION: Increasing numbers of women≥35 years of age rely on the individually adjusted risk figure to make a decision about invasive testing. The application of these selective procedures can reduce the rates of invasive testing with fewer losses of normal fetuses and led to an earlier diagnosis of aneuploidies.

A mixture model of nuchal translucency thickness in screening for chromosomal defects: validation of a single operator dataset.

OBJECTIVE: (1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach. METHODS: Database query, viable singletons [crown-rump length (CRL) 45-84 mm corresponding to 11-13(+6) weeks], December 1997 to November 2006, examined by Adam Gasiorek-Wiens, the statistical mixture model was applied. RESULTS: Seventy-four of 4171 were lost to follow-up (1.8%), 4097 singleton pregnancies included trisomy 21 (n = 34, 0.8%), trisomy 18 (n = 20, 0.5%), trisomy 13 (n = 8, 0.2%), Turner syndrome (n = 9, 0.2%) and other chromosomal abnormalities (n = 14, 0.3%). The main findings are that (1) the log-transformed NT measurements follow a mixture of two Gaussian distributions and (2) the criteria to apply either the delta-NT or log MoM models are not met. In the normal group, the majority of NT measurements were dependent on the CRL, a small group showed a median independent of the CRL. In the abnormal group it was the opposite. For a 5% false-positive rate (FPR), the trisomy 21 detection rate was 83%. CONCLUSIONS: The use of the mixture model in a single operator dataset produces results compatible with the original study. The mixture model has thus been validated.

Epignathus: always a simple teratoma? Report of an exceptional case with two additional fetiforme bodies.

We report on a case of a fetal epignathus combined with two fetus-like structures resembling acardius acranius. The anomaly was detected at 23 weeks of gestation and led to termination of pregnancy at 24 weeks. This is the first description of epignathus with parasitic fetuses detected prenatally. It shows that the boundary between fetal teratoma and multiple pregnancy in special cases may be difficult to define.

Screening for trisomy 21 by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks: a German multicenter study.

OBJECTIVE: To examine the effectiveness of screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum biochemistry using free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation. METHODS: This was a multicenter study of screening for trisomy 21 by a combination of maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of gestation, using the methodology developed by the Fetal Medicine Foundation. The distribution of estimated risks for trisomy 21 was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 were calculated. RESULTS: In total, 3864 singleton pregnancies with live fetuses at 11-14 weeks were examined and the fetal NT and maternal serum free beta-hCG and PAPP-A were successfully measured in all cases. The median maternal age was 33 (range 15-46) years and, in 1271 (35.8%), the age was 35 years or more, the median gestation at screening was 12 (11-14) weeks and the median fetal crown-rump length was 64 (range 45-84) mm. The fetal NT was above the 95th centile in 73.7% (14 of 19) of trisomy 21 and in 4.8% (169 of 3505) of normal pregnancies. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A was 1 in 300 or greater in 6.6% (233 of 3505) of normal pregnancies, in 84.2% (16 of 19) of those with trisomy 21 and 88.9% (24 of 27) of those with other chromosomal defects. CONCLUSIONS: In Germany, the results of screening for chromosomal defects by measurement of fetal NT and maternal serum biochemistry, in centers with appropriately qualified sonographers, are similar to those reported in the UK using the same methodology.

Autosomal recessive type of Adams-Oliver syndrome: prenatal diagnosis.

We report on three pregnancies complicated by Adams-Oliver syndrome in a consanguineous Turkish couple. Two cases were correctly diagnosed prenatally at 22+3 and 13+0 weeks gestation following the first case of Adams-Oliver syndrome in which severe anomalies of the extremities were observed at 26+5 weeks' gestation. In this first case, the diagnosis of Adams-Oliver syndrome was made following termination of pregnancy at 27+2 weeks' gestation. In all three cases, autopsy was performed. All fetuses showed anomalies of the extremities, aplasia cutis and symmetric defects of the skull, with bone being replaced by collagenous tissue. Although there have been numerous cases of the postnatal diagnosis of Adams-Oliver syndrome following termination of pregnancy, this is the first description of the prenatal diagnosis of this disorder.

Screening for trisomy 21 by fetal nuchal translucency and maternal age: a multicenter project in Germany, Austria and Switzerland.

OBJECTIVE: To examine the effectiveness of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation in Germany, Austria and Switzerland. METHODS: This was a multicenter study of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. All the sonographers involved in the study had received The Fetal Medicine Foundation Certificate of Competence in the 10-14-week scan. Fetal nuchal translucency thickness and crown-rump length were measured in 23 805 singleton pregnancies with live fetuses. In each case the risk for trisomy 21 was estimated on the basis of maternal age and fetal nuchal translucency thickness for crown-rump length with the use of The Fetal Medicine Foundation's software. The distribution of estimated risk was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 was calculated. RESULTS: Fetal nuchal translucency thickness was successfully measured in all 23 805 pregnancies and outcome was available in 21 959. The median maternal age was 33 (range 15-49) years and in 7935 (36.1%) the age was 35 years or greater. The median gestation at screening was 12 (10-14) weeks and the median fetal crown-rump length was 61 (range 38-84) mm. The estimated risk for trisomy 21 based on maternal age and fetal nuchal translucency thickness for crown-rump length was 1 in 300 or greater in 13.0% (2800 of 21 475) normal pregnancies, in 87.6% (184 of 210) of those with trisomy 21 and in 87.2% (239 of 274) with other chromosomal defects. CONCLUSIONS: In Germany, Austria and Switzerland the results of screening for chromosomal defects by measurement of fetal nuchal translucency thickness, in centers with appropriately qualified sonographers and using The Fetal Medicine Foundation's software, are similar to those reported in the UK using the same methodology.

Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments.

OBJECTIVE: This study assessed the efficacy of antidepressant treatment (sertraline) and group cognitive behavior therapy, alone or in combination, in primary dysthymia. The clinical features of dysthymia, as well as the functional impairments associated with the illness (e.g., quality of life, stress perception, coping styles), were evaluated. METHOD: Patients (N = 97) diagnosed with primary dysthymia, but no other current comorbid disorder, received either sertraline or placebo in a double-blind design over 12 weeks. In addition, a subgroup of the patients (N = 49) received a structured, weekly group cognitive behavior therapy intervention. RESULTS: Treatment with sertraline, with or without group cognitive behavior therapy, reduced the functional impairment of depression. The reductions were similar in the drug-cognitive therapy group and in subjects who received the drug alone. Furthermore, while group cognitive behavior therapy alone reduced the depression scores, this effect was not significantly greater than the effect of the placebo. The drug treatment also induced pronounced improvement in the functional measures, and in some respects these effects were augmented by group cognitive behavior therapy. Among patients who responded favorably to cognitive behavior therapy, the improvements in the functional measures were similar to those who responded to drug treatment, whereas such functional changes were not seen among patients who responded to placebo. CONCLUSIONS: Sertraline treatment effectively reduces the clinical symptoms and functional impairments associated with dysthymia. Although the group cognitive behavior therapy intervention was less effective in alleviating clinical symptoms, it augmented the effects of sertraline with respect to some functional changes, and in a subgroup of patients it attenuated the functional impairments characteristic of dysthymia.

Ellis-van Creveld syndrome: examination at 15 weeks' gestation.

In 1940, Ellis and van Creveld defined a syndrome they referred to as chondro-ectodermal dysplasia. This autosomal recessive condition, now usually referred to as Ellis-van Creveld syndrome (EVC), comprises bilateral postaxial polydactyly, a chondrodysplasia, characterized by shortness of limbs, and ectodermal dysplasia. Congenital heart defects are also common. There are many reports in medical literature describing affected newborns and even, older children. Here, we report the clinical, radiological and histological findings in a 15-week-old affected fetus. The diagnosis of Ellis-van Creveld syndrome in this fetus is based on a positive family history (an affected sib) and shortness of long bones as well as hexadactyly diagnosed by prenatal ultrasonography. On post-mortem examination, bilateral postaxial hexadactyly and symmetrical shortness of the long bones was noted. Histologically, there was too short a zone of cartilagineous columns in the metaphyses, a reduced number of chondrocytes and an irregularly structured spongiosa within the ossification zone. In addition, the fetus was found to have an atrio-ventricular canal. This heart defect is presumably rare in this syndrome. Other characteristic features such as small and dysplastic nails, sparse hair and abnormalities of the teeth were, of course, not yet present in this early developmental stage. In addition to EVC, the fetus had a 47,XXY chromosome constitution.

Efficacy and tolerability of venlafaxine in the treatment of primary dysthymia.

OBJECTIVE: Currently, there is no documentation of the efficacy of venlafaxine (a serotonin norepinephrine reuptake inhibitor) in the treatment of dysthymia. This open-label pilot investigation examined the efficacy and tolerability of venlafaxine in patients with primary dysthymia without concomitant major depression. METHODS: Fifteen patients were treated with venlafaxine for 12 weeks, with a dose range of 75 mg to 225 mg daily (taken orally), and symptom changes were measured using standard instruments including the Hamilton Depression Rating Scale (HAM-D). RESULTS: Significant changes from pretreatment to posttreatment were observed (p < 0.001). Using the standard criteria of a 50% reduction in HAM-D scores, 73.3% of patients were rated as responders. About two-thirds of the patients reported adverse events, which were mostly mild and brief in duration. CONCLUSION: Venlafaxine may be useful in the treatment of primary dysthymia but placebo-controlled studies are required for confirmation.

Preoperative anxiety in women.

Preoperative anxiety and fear can have adverse effects on patients' perioperative experiences. This study emerged from a larger study in which the researcher examined the perioperative experiences of women. The purpose of this study was to further investigate and describe the nature of preoperative anxiety in female subjects. This article reviews the literature on this topic, discusses the results, and explores the implications of anxiety and fear on the perioperative experience. The author offers suggestions to improve nurses' assessment of preoperative fear and anxiety and ways to lessen such feelings in patients.