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.

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.

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.

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.

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.

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.

Identification of fatty acids by electrospray mass spectrometry and tandem mass spectrometry.

Low-energy negative-ion electrospray mass spectrometry (ESI-MS) and ESI-MS/MS were used to characterize saturated and unsaturated fatty acids. The carbon number and degree of unsaturation of fatty acids were determined using ESI-MS, and MS/MS was used to localize some double bond positions of mono-and polyunsaturated fatty acids. For compounds with up to two unsaturated bonds, fragmentation was dominated by loss of H2O from the carboxyl moiety and very low-intensity peaks generated from bonds cleaved at carbons alpha and/or beta to sites of unsaturation. Fragmentation of monounsaturated fatty acids was minimal using this soft method of mass spectrometric analysis, but increased with progressively greater degrees of fatty acid unsaturation. There was extensive hydride migration during ESI-MS/MS of compounds with three or more double bonds. Although this behavior complicated localization of double and triple bonds, the spectra were reproducible. Many peaks could not be definitively assigned to specific product ions, but the spectra of standards and complementary natural products were similar and isobaric compounds could be differentiated. The utility of this technique to examine biological samples was shown by analysis of the fatty acid composition of cod liver oil. Detection limits for negative-ion ESI-MS/MS were at or below 1 pg.

Assessing depression in fibromyalgia patients.

PURPOSE: This study investigated the relationships among four methods of detecting depression in patients with fibromyalgia. METHODS: Data were obtained from 100 women (mean age 43 years) who had been diagnosed with fibromyalgia. Instruments included a computerized Diagnostic Interview Schedule (C-DIS), Beck Depression Inventory (BDI), an adjusted "disease-free" BDI (BDI-A), and Minnesota Multiphasic Personality Inventory depression subscale (MMPI-D). Chance-corrected concordance, sensitivity, specificity, and accuracy among the four methods were calculated. RESULTS: The C-DIS detected 22% and BDI-A 29% with current major depression. The BDI and MMPI-D yielded higher estimates of 55% of the 44%, respectively. Agreement on the diagnosis among the four methods was significantly greater than chance. When compared with the C-DIS, the BDI was the most sensitive instrument and the BDI-A most specific.

Fast onset: an open study of the treatment of major depressive disorder with nefazodone and pindolol combination therapy.

Pindolol, a beta-adrenergic and presynaptic 5-HT1 vA antagonist, when added to specific serotonin reuptake inhibitors, potentiates the antidepressant action, leading to an earlier onset of effect. Following on from the suggestion that nefazodone, a specific serotonin reuptake inhibitor and antagonist of 5-HT2, improves 5-HT1A-mediated transmission, we used a pindolol and nefazodone combination treatment for major depressive disorder. Twenty outpatients underwent a 4-week trial. Patients were seen twice a week, and completed efficacy and safety measures including the 17-item Hamilton Depression Scale, the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression scales. Results demonstrated significant improvement in all efficacy measures after one visit (2-4 days of treatment), with decreasing depression scores on all measures continuing throughout the trial. After 1 week of treatment, 15 out of 20 patients had experienced a 50% or greater reduction in their 17-item Hamilton Depression Scale scores. Remission rates were dramatic, with 40% of patients in remission after 1 week of treatment and 90% after 4 weeks. This open study of nefazodone-pindolol combination therapy suggests that this may be a new treatment option for patients with major depressive disorder; however, it needs to be replicated in a double-blind trial before conclusions regarding efficacy and safety can be made.

Sterol and steryl ester regulation of phospholipase A2 from the mosquito parasite Lagenidium giganteum.

Lagenidium giganteum, a facultative parasite of mosquito larvae, cannot synthesize sterols, and requires an exogenous source of these lipids in order to enter its reproductive cycle. This parasite grows vegetatively in the absence of sterols, but requires cholesterol or structurally related compounds to produce motile zoospores, which are the only stage capable of infecting mosquitoes. Sterols structurally related to cholesterol and some steryl esters inhibited the activity of L. giganteum phospholipase A2 (PLA2), an enzyme that hydrolyzes fatty acids from the sn-2 position of glycerophospholipids. Sterols that induce reproduction inhibited L. giganteum PLA2 activity, while sterols and steroids that do not support sporulation had minimal effect. Most steryl esters had no effect on enzyme activity, but cholesteryl arachidonate (CA) was a potent inhibitor of parasite PLA2. Not all enzymes partly purified using a DEAE-Sephacel column were affected by these lipids, demonstrating selective inhibition of specific enzymes. Potency was enhanced by up to several orders of magnitude if epoxy fatty acids were esterified to the cholesterol nucleus. The steryl ester pool was dynamic during morphogenesis, and the fatty acid composition of the steryl esters did not mimic total cell or membrane (glycerophospholipid) fatty acid composition as L. giganteum proceeded through its growth cycle. Synthesis of CA and monoepoxy CA by the parasite was confirmed using electrospray mass spectrometry and collision-induced dissociation. Steryl derivatives selectively inhibited PLA2 enzymes from bovine pancreas, snake venom, and human cytoplasmic 85-kDa PLA2.

Pharmacological aversive counterconditioning to alcohol in a private hospital; one-year follow-up.

Of 261 patients treated for alcoholism with pharmacological aversive counterconditioning, 63% remained abstinent for 1 year following treatment.

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.

Neuropsychological functioning after prolonged high altitude exposure in mountaineering.

This prospective study examined the possibility of long lasting CNS sequelae of high altitude exposure in mountaineering. An extensive battery of neuropsychological and personality tests was given to 22 subjects before and after Himalayan climbs above 5334 m (17,500 ft). All subjects were at altitude for long periods without supplemental oxygen, but did not suffer other physical insults such as serious injury or food or water deprivation. Although several climbers experienced acute effects of mountain sickness while at altitude, their post-climb evaluations revealed no evidence of lasting cerebral dysfunction or psychological deficit. A few climbers' subjective ratings of mental functioning were worse after their expeditions, but these self-assessments were unsupported by their performances on the objective testing. It was concluded that in healthy people who do not suffer other physical insults as well, acute CNS effects of low oxygen tensions during high altitude climbs are reversible.

Patient autonomy in care: a theoretical framework for nursing.

Patient autonomy has increasingly become an issue in a health care system that often promotes dependence in decision making. The complex technology of health care creates situations in which difficult decisions need to be made by patients and their families. Nurses are important participants in that decision-making process. Models available for developing a theoretical approach to patient autonomy traditionally have been limited to ethics literature. A more recent approach to personal autonomy is Meyer's philosophical feminist perspective. Any philosophical approach to patient autonomy must be congruent with other critical nursing concepts. In addition, a model of patient autonomy for nursing must be useful for persons who operate at various functional levels. The model, Patient-Autonomy in Care, based on the Meyer's model, was developed to incorporate the special vulnerability and functional needs of patients in the health care system.

A rationale and method for the sexual history in family practice.

The taking of a sexual history produces a therapeutic effect for the patient by giving the patient permission to be sexual, filling patient knowledge gaps, providing a reality check, and beginning the process of self-acceptance by the patient. The physician's own empathy may seem to interfere with his feeling comfortable while eliciting a sexual history; at the same time the patient may struggle with feelings of shame and embarrassment. The physician can alleviate patient discomfort by being accepting and empathetic, and by assuming the patient has thought, felt, and done everything in the sexual area. He can also help by beginning with general questions, avoiding "why" questions and jargon, and gently reporting inconsistencies.

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.