This study evaluated the ability of two Doppler ultrasound-derived parameters, the carotid corrected flow time (FTc) and respirophasic variation in carotid artery blood flow peak velocity (ΔVpeak), ...to predict fluid responsiveness in spontaneously breathing patients.
A total of 53 spontaneously breathing patients were studied before anaesthetic induction for neurosurgery. Carotid FTc, ΔVpeak, and haemodynamic data were measured before and after administration of 6 ml kg−1 colloid. Fluid responsiveness was defined as a 15% or more increase in stroke volume index as assessed by transthoracic echocardiography after the fluid challenge.
Twenty-two (42%) patients were fluid responders. The areas under the receiver operating characteristic curves for FTc and ΔVpeak were 0.842 95% confidence interval (CI) 0.735–0.948, P<0.001 and 0.818 (95% CI: 0.701–0.935, P<0.001), respectively. The optimal cut-off values of FTc and ΔVpeak for fluid responsiveness were 349.4 ms (sensitivity of 72.7%; specificity of 83.9%) and 9.1% (sensitivity of 72.7%; specificity of 87.1%), respectively. The grey zone for FTc was 346.9–361.0 ms and included 28% of the patients, and the grey zone for ΔVpeak was 6.5–10.2% and included 50% of the patients.
Using Doppler ultrasound-derived parameters measured at the carotid artery, FTc predicted fluid responsiveness in spontaneously breathing patients better than ΔVpeak. However, further studies are warranted before these parameters are recommended for clinical use.
NCT 02843477.
The presence of the nucleic acid of the spotted fever group (SPG) and typhus group (TG) rickettsiae was investigated in 200 serum specimens seropositive for SFG rickettsiae by multiplex-nested ...polymerase chain reaction with primers derived from the rickettsial outer membrane protein B gene. The DNA of SFG, TG, or both rickettsiae was amplified in the 24 serum specimens, and sequence analysis showed Rickettsia conorii, R. japonica, and R. felis in the specimens. R. conorii and R. typhi were found in 7 serum specimens, which indicated the possibility of dual infection in these patients. These findings suggest that several kinds of rickettsial diseases, including boutonneuse fever, rickettsialpox, R. felis infection, and Japanese spotted fever, as well as scrub typhus and murine typhus, are occurring in Korea.
Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide ...drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein.
We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis.
In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants 41% vs. 0 of 27 0%, P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants 51% vs. 0 of 37 0%), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P=0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups.
Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074 .).
We perform a joint analysis of the counts and weak lensing signal of redMaPPer clusters selected from the Dark Energy Survey (DES) Year 1 dataset. Our analysis uses the same shear and source ...photometric redshifts estimates as were used in the DES combined probes analysis. Our analysis results in surprisingly low values for S8 = σ8 (Ωm/0.3)0.5 = 0.65 ± 0.04, driven by a low matter density parameter, Ωm = 0.179+0.031−0.038, with σ8 − Ωm posteriors in 2.4σ tension with the DES Y1 3x2pt results, and in 5.6σ with the Planck CMB analysis. These results include the impact of post-unblinding changes to the analysis, which did not improve the level of consistency with other data sets compared to the results obtained at the unblinding. The fact that multiple cosmological probes (supernovae, baryon acoustic oscillations, cosmic shear, galaxy clustering and CMB anisotropies), and other galaxy cluster analyses all favor significantly higher matter densities suggests the presence of systematic errors in the data or an incomplete modeling of the relevant physics. Cross checks with x-ray and microwave data, as well as independent constraints on the observable-mass relation from Sunyaev-Zeldovich selected clusters, suggest that the discrepancy resides in our modeling of the weak lensing signal rather than the cluster abundance. Repeating our analysis using a higher richness threshold (λ ≥ 30) significantly reduces the tension with other probes, and points to one or more richness-dependent effects not captured by our model.
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