that could modify early mortality.Aim Compare the opinion of paediatric consultants to paediatric Senior House Officers (SHOs) with regards their perceived level of preparedness for starting work in paediatrics. Methods A 5-point Likert scale questionnaire was administered to paediatric consultants and SHOs investigating how well they considered the SHO was performing and how well prepared the SHO perceived themselves for work in clinical paediatrics, respectively. Questions related to procedures, clinical examination, teamwork, history taking and OPD related activity. Results 50 Consultants and 75 SHOs completed the questionnaire. Using a Mann-Whitney U test, both groups answered similarly to questions relating to clinical examination and history taking (p=0.51 and p=0.15). Selleckchem MS023 However, there were significant differences in their responses to questions relating to procedures, teamwork and OPD related activity (p less then 0.05). Conclusion There is a significant disparity between consultant opinion of ability and SHOs perception of preparedness for some of the same skills. More work, focusing on these specific aspects of undergraduate paediatric education needs to be carried out to improve graduate preparedness for this role.

A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes.

In a 16-week, multicenter, randomized, open-label, parallel-group trial, we assigned, in a 31 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring.

A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop groupcose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT03844789.).

mutations occur in 70% of medullary thyroid cancers, and

fusions occur rarely in other thyroid cancers. In patients with

-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown.

We enrolled patients with

-mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated

fusion-positive thyroid cancer, in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response), as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety.

In the first 55 consecutively enrolled patients with

-mutant medullary thyroid cancer who had previously received vandetanib, cabozantinib, or both, the percentage who had a response was 69% (95% confidence interval [CI], 55 to 81), and 1-year progression-free survival was 82% (95% CI, 69 to 90). In 88 patients with

-mutant medus.gov number, NCT03157128.).

In this phase 1-2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).

fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with

fusion-positive NSCLC, the efficacy and safety of selective RET inhibition are unknown.

We enrolled patients with advanced

fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated separately in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety.

In the first 105 consecutively enrolled patients with

fusion-positive NSCLC who had previously received at least platinum-based chemotherapy, the percentage with an objective response was 64% (95% confidence interval [CI], 54 to 73). The median duration of response was 17.5 months (95% CI, 12.0 to could not be evaluated), and 63% of the responses were ongoing at a median follow-up of 12.1 28.).

Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).

Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses.

We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt.

CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.