Barriers to Pediatric Postoperative Pain Management-Interprofessional Focus Group Interviews.

Background: Historically, postoperative pain management of children in hospitals has been inadequate, despite advancements in pain physiology and management. Postoperative pain correlates with increased complications, psychological harm, and parental stress, leading to inefficiencies in resource utilization and prolonged hospital stays. Effective pain management relies on organizational, collaborative, and individual efforts, with interprofessional communication and cooperation being crucial.

The use and prevention of procedural restraint in children - A scoping review.

Problem: In healthcare facilities, restraint may be used on children to perform treatments or procedures. Restraint can be harmful, and little is known about how to prevent the use of restraint during medical procedures. A scoping review was conducted to find and map knowledge about (1) the use and prevention of restraint and (2) approaches, such as interventions and guidelines, available to prevent the use of restraint.

Principles for Defining Estimands in Clinical Trials-A Proposal.

The ICH E9(R1) guideline outlines the estimand framework, which aligns planning, design, conduct, analysis, and interpretation of a clinical trial. The benefits and value of using this framework in clinical trials have been outlined in the literature, and guidance has been provided on how to choose the estimand and define the estimand attributes. Although progress has been made in the implementation of estimands in clinical trials, to the best of our knowledge, there is no published discussion on the basic principles that estimands in clinical trials should fulfill to be well defined and consistent with the ideas presented in the ICH E9(R1) guideline.

Nursing leaders' perspectives on research in specialist health services: A descriptive study.

Aim: This study is to gain insight into how nursing leaders perceive their contribution to research-based knowledge in hospital settings.

Design: The study has a qualitative descriptive design.

Methods: Nine nursing leaders were interviewed.

Choice of time scale for analysis of recurrent events data.

Recurrent events refer to events that over time can occur several times for each individual. Full use of such data in a clinical trial requires a method that addresses the dependence between events. For modelling this dependence, there are two time scales to consider, namely time since start of the study (running time) or time since most recent event (gap time).

Lifespans of Twins: Does Zygosity Matter?

Studies with twins provide fundamental insights to lifespans of humans. We aim to clarify if monozygotic and dizygotic twin individuals differ in lifespan, that is, if zygosity matters. We investigate whether a possible difference in mortality after infancy between zygosities is stable in different age cohorts, and whether the difference remains when twins with unknown zygosity are taken into account.

Influence of Disease Duration on Circulating Levels of miRNAs in Children and Adolescents with New Onset Type 1 Diabetes.

Circulating microRNAs (miRNAs) have been implicated in several pathologies including type 1 diabetes. In the present study, we aimed to identify circulating miRNAs affected by disease duration in children with recent onset type 1 diabetes. Forty children and adolescents from the Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12, and 60 months after diagnosis.

Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes?

Introduction: The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However, a large number of researchers avoid providing such care based largely on anecdotal opinions that it might interfere with model pathophysiology in the longer term.

Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus.

Aims/hypothesis: We aimed to identify circulating microRNA (miRNA) that predicts clinical progression in a cohort of 123 children with new-onset type 1 diabetes mellitus.

Methods: Plasma samples were prospectively obtained at 1, 3, 6, 12 and 60 months after diagnosis from a subset of 40 children from the Danish Remission Phase Cohort, and profiled for miRNAs. At the same time points, meal-stimulated C-peptide and HbA levels were measured and insulin-dose adjusted HbA (IDAA) calculated.

Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia: The HypoAna trial.

Aim: Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night.

Increased mortality in a Danish cohort of young people with Type 1 diabetes mellitus followed for 24 years.

Aim: To determine the mortality rate in a Danish cohort of children and adolescents diagnosed with Type 1 diabetes mellitus compared with the general population.

Methods: In 1987 and 1989 we included 884 children and 1020 adolescents aged 20 years and under, corresponding to 75% of all Danish children and adolescents with Type 1 diabetes, in two nationwide studies in Denmark. Those who had participated in both investigations (n = 720) were followed until 1 January 2014, using the Danish Civil Registration System on death certificates and emigration.

Confidence bounds for nonlinear dose-response relationships.

An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve.

Testing effect of a drug using multiple nested models for the dose-response.

During development of a drug, typically the choice of dose is based on a Phase II dose-finding trial, where selected doses are included with placebo. Two common statistical dose-finding methods to analyze such trials are separate comparisons of each dose to placebo (using a multiple comparison procedure) or a model-based strategy (where a dose-response model is fitted to all data). The first approach works best when patients are concentrated on few doses, but cannot conclude on doses not tested.

Partial remission definition: validation based on the insulin dose-adjusted HbA1c (IDAA1C) in 129 Danish children with new-onset type 1 diabetes.

Objective: To validate the partial remission (PR) definition based on insulin dose-adjusted HbA1c (IDAA1c).

Subjects And Methods: The IDAA1c was developed using data in 251 children from the European Hvidoere cohort. For validation, 129 children from a Danish cohort were followed from the onset of type 1 diabetes (T1D).

Effect of insulin analogues on risk of severe hypoglycaemia in patients with type 1 diabetes prone to recurrent severe hypoglycaemia (HypoAna trial): a prospective, randomised, open-label, blinded-endpoint crossover trial.

Background: Insulin analogues have been developed to reduce the risk of hypoglycaemia in patients with diabetes who require insulin-based treatment, but their effect on this endpoint in patients with type 1 diabetes complicated by recurrent severe hypoglycaemia is unknown. We compared the occurrence of severe hypoglycaemic episodes in such patients during treatment with insulin analogues or human insulin.

Methods: In this investigator-initiated, prospective, randomised, open-label, blinded-endpoint crossover trial at seven medical centres in Denmark, we recruited patients (aged ≥18 years) with type 1 diabetes (diagnosed for >5 years) who had reported two or more episodes of severe hypoglycaemia in the preceding year.

Disease progression among 446 children with newly diagnosed type 1 diabetes located in Scandinavia, Europe, and North America during the last 27 yr.

Objective: To clarify whether the rate of decline in stimulated C-peptide (SCP) from 2 to 15 months after diagnosis has changed over an interval of 27 yr.

Research Design And Methods: The rate of decline in SCP levels at 1, 2, 3, 6, 9, 12, and 15 months after diagnosis was compared in four paediatric cohorts from Scandinavian and European countries including 446 children with new onset type 1 diabetes (T1D, 1982-2004). Findings were evaluated against 78 children (2004-2009) from the TrialNet studies.

Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression.

This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n = 275 and 129, resp.

Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes.

Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes.

Relationship between ZnT8Ab, the SLC30A8 gene and disease progression in children with newly diagnosed type 1 diabetes.

Autoantibodies against the newly established autoantigen in type 1 diabetes, zinc transporter 8, ZnT8, are presented as two types, ZnT8RAb and ZnT8WAb. The rs13266634 variant of the SLC30A8 gene has recently been found to determine the type of ZnT8Ab. The aim of this study was to explore the impact of this genetic variant and the ZnT8Ab on the residual beta-cell function during disease progression the first year after disease diagnosis in children with newly diagnosed type 1 diabetes.

The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes.

Background: The protein tyrosine phosphatase nonreceptor type 2 (PTPN22) has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c), glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA) and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab) in children during the first year after diagnosis of type 1 diabetes.

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies.

Background: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes.

Materials And Methods: In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis.

Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis.

Objective: To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D).

Subjects And Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal-stimulated C-peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally.

New definition for the partial remission period in children and adolescents with type 1 diabetes.

OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual beta-cell function.