Callesenmullen8480

Children with medical comorbidities are at greater risk for severe influenza and poorer clinical outcomes. Despite recommendations and funding, influenza vaccine coverage remains inadequate in these children.

We aimed to systematically review literature assessing interventions targeting influenza vaccine coverage in children with comorbidities and assess the impact on influenza vaccine coverage.

PubMed, Scopus, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, and Web of Science databases were searched.

Interventions targeting influenza vaccine coverage in children with medical comorbidities.

Two reviewers independently screened articles, extracting studies' methods, interventions, settings, populations, and results. Four reviewers independently assessed risk of bias.

From 961 screened articles, 35 met inclusion criteria. Published studies revealed that influenza vaccine coverage was signifibserved. Future well-designed studies evaluating the effectiveness of different intervention are required to inform future optimal interventions.

Cardiovascular risk factors, such as obesity, blood pressure, and physical inactivity, have been identified as modifiable determinants of left ventricular (LV) diastolic function in adulthood. However, the links between childhood cardiovascular risk factor burden and adulthood LV diastolic function are unknown. To address this lack of knowledge, we aimed to identify childhood risk factors associated with LV diastolic function in the participants of the Cardiovascular Risk in Young Finns Study.

Study participants (

= 1871; 45.9% men; aged 34-49 years) were examined repeatedly between the years 1980 and 2011. We determined the cumulative risk exposure in childhood (age 6-18 years) as the area under the curve for systolic blood pressure, adiposity (defined by using skinfold and waist circumference measurements), physical activity, serum insulin, triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterols. Adulthood LV diastolic function was defined by using E/é ratio.

Elevated systolic blood pressure and increased adiposity in childhood were associated with worse adulthood LV diastolic function, whereas higher physical activity level in childhood was associated with better adulthood LV diastolic function (

< .001 for all). The associations of childhood adiposity and physical activity with adulthood LV diastolic function remained significant (both

< .05) but were diluted when the analyses were adjusted for adulthood systolic blood pressure, adiposity, and physical activity. The association between childhood systolic blood pressure and adult LV diastolic function was diluted to nonsignificant (

= .56).

Adiposity status and the level of physical activity in childhood are independently associated with LV diastolic function in adulthood.

Adiposity status and the level of physical activity in childhood are independently associated with LV diastolic function in adulthood.

To determine whether MS disease-modifying therapies (DMTs) can be safely discontinued in patients aged 50 years or older with suspected benign/burnt-out MS and to define criteria to identify such patients.

We conducted a retrospective cohort study of 136 patients with suspected benign/burnt-out MS who discontinued DMTs from the electronic health record (EHR) at Kaiser Permanente Southern California.

The majority discontinued an injectable DMT (n = 131, 96%). At the time of DMT discontinuation, mean and SD for age was 60.6 (6.2) years, disease duration 19.5 (10.7) years, and time since last relapse 11.0 (7.2) years. After a mean duration of follow-up of 5.0 years post-DMT discontinuation, 5 (3.7%) patients had a relapse, 2 (1.5%) had mild residual deficits, and 3 (2.2%) had asymptomatic MRI disease activity. Patients with MS disease activity following DMT discontinuation were younger (median = 53.6 years) than those who remained disease activity free. Fifty patients (36.8%) had only 1 lifetime relapse, of whom 1 relapsed post-DMT discontinuation. Sixty (56.6%) of 106 patients with spinal cord MRIs before discontinuation showed demyelinating lesions.

DMT discontinuation in older patients with suspected benign/burnt-out MS appears safe. Our findings suggest that MRI evidence of spinal cord involvement does not preclude the possibility of benign/burnt-out MS, and for those with 2 or more lifetime relapses, a benign/burn-out classification is best reserved for those aged 55 years and older. Future studies to determine whether DMT discontinuation is safe at a younger age in patients with a single lifetime relapse are needed.

The study provides Class IV evidence that DMTs can be safely discontinued in older patients with suspected benign/burnt-out MS.

The study provides Class IV evidence that DMTs can be safely discontinued in older patients with suspected benign/burnt-out MS.

Despite the acknowledged benefits of research, Palliative Medicine receives minimal research funding and has few dedicated research training posts. This study investigated the opportunities and barriers to participating in research for the current cohort of UK Palliative Medicine Specialist Trainees (PMSTs), to better understand the opportunities to improve evidence-based practice within the specialty.

Two surveys, one for PMSTs and a second for training programme directors (TPDs), were developed. Surveys were piloted and then reviewed by the UK Palliative trainee Research Collaborative and the Palliative Medicine Specialty Advisory Committee (SAC) before distribution. All current PMSTs and TPDs representing all of the UK training regions (n=13) were invited to complete the appropriate survey.

Overall, 85% (11/13) and 45% (102/225) of TPDs and PMSTs responded, respectively. Almost all (92%) PMSTs reported that they were either 'very interested' or 'quite interested' in taking part in clinical research. PMSTs generally felt that educationaland clinical supervisors were supportive of them taking part in research; however, few (35%) believed they had access to personnel with adequate research experience to provide practical support. Opportunity for appropriate research supervision varied considerably by training region. Where research was being conducted, it was often conducted in trainees' personal time due to the wide regional variation in dedicated research time.

Despite significant interest in clinical research and support by TPDs and clinical supervisors, access to experienced researchers and equitable protected research time by region needs urgent attention to enhance progress in evidence-based palliative medicine.

Despite significant interest in clinical research and support by TPDs and clinical supervisors, access to experienced researchers and equitable protected research time by region needs urgent attention to enhance progress in evidence-based palliative medicine.Although it is self-evident that education in neurology is important and necessary, how to fund the educational mission is a frequent challenge for neurology departments and clinicians. Department chairs often resort to a piecemeal approach, cobbling together funding for educators from various sources, but frequently falling short. Here, we review the various sources available to fund the educational mission in neurology, understanding that not every department will have access to every source. We describe the multiple different teaching models and formats used by the modern student and educator and their associated costs, some of which are exorbitant. We discuss possible nonfinancial incentives, including pathways to promotion, educational research, and other awards and recognition. Neurological education is commonly underfunded, and departments and institutions must be nimble and creative in finding ways to fund the time and effort of educators.The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is global and unprecedented. Although remdesivir has recently been approved by the FDA to treat SARS-CoV-2 infection, no oral antiviral is available for outpatient treatment. AT-527, an orally administered double prodrug of a guanosine nucleotide analog, was previously shown to be highly efficacious and well tolerated in hepatitis C virus (HCV)-infected subjects. Here, we report the potent in vitro activity of AT-511, the free base of AT-527, against several coronaviruses, including SARS-CoV-2. In normal human airway epithelial cells, the concentration of AT-511 required to inhibit replication of SARS-CoV-2 by 90% (EC90) was 0.47 μM, very similar to its EC90 against human coronavirus (HCoV)-229E, HCoV-OC43, and SARS-CoV in Huh-7 cells. Little to no cytotoxicity was observed for AT-511 at concentrations up to 100 μM. Substantial levels of the active triphosphate metabolite AT-9010 were formed in normal human bronchial and nasal epithelial cells incubated with 10 μM AT-511 (698 ± 15 and 236 ± 14 μM, respectively), with a half-life of at least 38 h. Results from steady-state pharmacokinetic and tissue distribution studies of nonhuman primates administered oral doses of AT-527, as well as pharmacokinetic data from subjects given daily oral doses of AT-527, predict that twice daily oral doses of 550 mg AT-527 will produce AT-9010 trough concentrations in human lung that exceed the EC90 observed for the prodrug against SARS-CoV-2 replication. This suggests that AT-527 may be an effective treatment option for COVID-19.Linezolid is an oxazolidinone antibiotic exhibiting efficacy against multidrug-resistant (MDR) Gram-positive-related infections. However, its population pharmacokinetic (PopPK) profile in Chinese critically ill children has not been characterized. Optimal dosing regimens should be established according to the PopPK/pharmacodynamic(PD) properties of linezolid in the specific population. UAMC-3203 manufacturer This work aims to describe the pharmacokinetic (PK) properties of linezolid, assess the factors affecting interpatient variability, and establish an optimized regimen for children in pediatric intensive care unit (PICU). A single-center, prospective, open-labeled PK study was performed. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to measure the plasma levels during linezolid treatment. PopPK analysis was conducted using Phoenix NLME software. Sixty-three critically ill pediatric patients were included. The data showed good fit for a two-compartment model with linear elimination. Bodl children were evaluated, and an optimal dosage regimen was constructed based on developmental PopPK/PD model and simulation. (This study has been registered in the Chinese Clinical Trial Registry under no. ChiCTR1900021386.).BACKGROUND.Candida auris has demonstrated the ability to colonize the skin of hospitalized patients, possibly contributing to nosocomial spread. OBJECTIVE. The objective was to determine whether two novel transdermal agents could clear skin colonization established by C. aurisMETHODS. A murine skin colonization model was first optimized and then used to test fungal burden reduction following treatment with 1% terbinafine or 1% clotrimazole in a proprietary Advanced Penetration Technology formulation (APT™). RESULTS. Both treatments significantly reduced fungal burden compared to control groups. CONCLUSION. These novel agents show promise as a topical means of preventing skin colonization by C. auris.