Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

Public and Private Hospitals in Kuala Lumpur and Selangor, Malaysia: How Do They Fare in Terms of Accessibility for the Physically Disabled?

Public and private hospitals in Kuala Lumpur and Selangor were evaluated in terms of their accessibility for the physically disabled. The research hypotheses for this study included the following: (1) Both types of hospitals are accessible for the physically disabled as measured by specifi c criteria but (2) the degree of accessibility is higher in the case of private hospitals as compared to public hospitals. A total of 23 private hospitals and 11 public hospitals in Kuala Lumpur and Selangor were invited to participate in the study. The 5 private hospitals and 5 public hospitals that agreed were evaluated for adequacy of facilities for the physically-disabled. For this purpose, 13 specifi c criteria were assessed and scored for each hospital. These criteria were also grouped into 5 categories, namely, parking, toilet, door and lift, corridor and ramp. Scores were compared between each hospital and then aggregated and compared for private hospitals versus public hospitals. It was found that none of the 5 private hospitals and 5 public hospitals studied satisfi ed 100% of the criteria evaluated. Looking at each hospital individually, the overall scores range from 32% to 92% for the criteria set. Only 4 of the 10 hospitals in our sample achieved overall scores of 80% or higher in terms of the evaluation criteria we used. With the exception of availability of ramps where public hospitals scored slightly higher ,for most of the individual criterion, private hospitals scored higher than public hospitals. Looking at each criterion across all hospitals, the scores range from 59.2% (adequacy of parking) to 85% (adequacy of corridors). The median score obtained by private hospitals and by public hospitals for all 13 criteria were analysed for any difference. The difference between private hospitals and public hospitals is not statistically signifi cant (Mann-Whitney U = 6.5, p-value = 0.099). There is no signifi cant difference between Kuala Lumpur/Selangor private and public hospitals in terms of accessibility for physically disabled people. However, some hospitals are more accessible for the physically disabled than other hospitals. These fi ndings indicate that there is room for improvement.

Influence of microRNA deregulation on chaperone-mediated autophagy and α-synuclein pathology in Parkinson's disease.

The presence of α-synuclein aggregates in the characteristic Lewy body pathology seen in idiopathic Parkinson's disease (PD), together with α-synuclein gene mutations in familial PD, places α-synuclein at the center of PD pathogenesis. Decreased levels of the chaperone-mediated autophagy (CMA) proteins LAMP-2A and hsc70 in PD brain samples suggests compromised α-synuclein degradation by CMA may underpin the Lewy body pathology. Decreased CMA protein levels were not secondary to the various pathological changes associated with PD, including mitochondrial respiratory chain dysfunction, increased oxidative stress and proteasomal inhibition. However, decreased hsc70 and LAMP-2A protein levels in PD brains were associated with decreases in their respective mRNA levels. MicroRNA (miRNA) deregulation has been reported in PD brains and we have identified eight miRNAs predicted to regulate LAMP-2A or hsc70 expression that were reported to be increased in PD. Using a luciferase reporter assay in SH-SY5Y cells, four and three of these miRNAs significantly decreased luciferase activity expressed upstream of the lamp-2a and hsc70 3'UTR sequences respectively. We confirmed that transfection of these miRNAs also decreased endogenous LAMP-2A and hsc70 protein levels respectively and resulted in significant α-synuclein accumulation. The analysis of PD brains confirmed that six and two of these miRNAs were significantly increased in substantia nigra compacta and amygdala respectively. These data support the hypothesis that decreased CMA caused by miRNA-induced downregulation of CMA proteins plays an important role in the α-synuclein pathology associated with PD, and opens up a new avenue to investigate PD pathogenesis.

Optofluidic variable-focus lenses for light manipulation.

This paper presents a planar optofluidic lens for light manipulation utilizing a combination of optofluidic biconvex lens with micromixer. Three light manipulation techniques including tunable optical diverging, collimating and focusing are realized by altering the refractive index of the optofluidic variable-focus lenses formed by solid polydimethylsiloxane (PDMS) walls and tunable liquid lens body. The optical power from the laser input can be increased or decreased with the tuning of the variable-focus lenses' refractive indexes. The optical power adjustment capabilities are demonstrated and characterized. The combinations of benefits of all lens' optical manipulation capabilities, greater mechanical stability, significant increase of optofluidic device's life time and seamless integration with other lab-on-a-chip functionalities provide a promising and versatile optofluidic compartment to integrate with lab-on-a-chip excitation and sensing applications. Optofluidic lens-including system for tunable fluorescence sensing is demonstrated showing 186% increase in detected fluorescence intensity.

Patients with pelvic fracture: what factors are associated with mortality?

BACKGROUND: Pelvic fracture is one of the major injuries that lead to death in patients who sustain high-impact injuries such as road traffic accidents and falls from height. AIMS: This study aims to look at the epidemiology and the significant predictors of mortality in victims with pelvic fracture presenting to the emergency department (ED) of an urban Asian city. METHODS: This was a retrospective data analysis of all trauma patients with pelvic fracture who were treated at the ED of an urban adult hospital in Singapore from April 2001 to December 2004. Student's t-test and χ(2) test were used in statistical analysis where appropriate. RESULTS: The study included 179 consecutive patients. Sixty-four percent of patients were males, and 71% of patients were in the 20-49-year-old age group. Road traffic accidents and falls from height were the two most common mechanisms of injury. Mortality rate was 37%. Pelvic fracture severity, shock and coma at presentation, and the presence of concurrent head and chest injuries were associated with increased mortality. Gender, other mechanisms of injury and other concomitant injuries were not associated with increased mortality. CONCLUSIONS: The mortality rate of trauma patients with pelvic fracture continues to be high. In such patients, predictors of mortality are the severity of the pelvic fracture, the presence of coma, shock, and head and chest injuries.

Efficacy of community-based multidisciplinary disease management of chronic heart failure.

INTRODUCTION: A multidisciplinary disease management (DM) programme in chronic heart failure (CHF) improves clinical outcome. The efficacy of such a programme in a heterogeneous Asian community is not well established. Therefore, we undertook the evaluation of the efficacy of the multidisciplinary community-based DM CHF programme. METHODS: This was a prospective study involving 154 patients (54 percent male) with a primary diagnosis of CHF, New York Heart Association functional class III/IV CHF, with left ventricular ejection fraction (LVEF) less than 40 percent. The mean age was 65 +/- 12 years and mean LVEF was 27 +/- 9 percent. We evaluated CHF hospitalisation, quality of life, activity status and quality of care (percentage of patients who received ACE inhibitors/angiotensin receptor blockers (ARB) and beta blockers after a period of six months. RESULTS: At six months, there was improvement in the quality of life and activity status (p < 0.001). ACE inhibitors/ARB were maintained in 97 percent of the patients and there was an increased usage of beta blockers (p-value equals 0.001). The rate of CHF hospitalisation was reduced by 68 percent (p-value is less than 0.001) and there was no mortality. CONCLUSION: The multidisciplinary DM of CHF in a heterogeneous Asian community showed significant improvement in quality of life, quality of care and reduction in CHF hospitalisation.