Aims/hypothesis
This study aimed to systematically review what has been reported on the incidence and prevalence of type 2 diabetes in children and adolescents, to scrutinise the methodological ...issues observed in the included studies and to prepare recommendations for future research and surveillances.
Methods
PubMed, the Cochrane Database of Systematic Reviews, Scopus, EMBASE and Web of Science were searched from inception to February 2013. Population-based studies on incidence and prevalence of type 2 diabetes in children and adolescents were summarised and methodologically evaluated. Owing to substantial methodological heterogeneity and considerable differences in study populations a quantitative meta-analysis was not performed.
Results
Among 145 potentially relevant studies, 37 population-based studies met the inclusion criteria. Variations in the incidence and prevalence rates of type 2 diabetes in children and adolescents were mainly related to age of the study population, calendar time, geographical regions and ethnicity, resulting in a range of 0–330 per 100,000 person-years for incidence rates, and 0–5,300 per 100,000 population for prevalence rates. Furthermore, a substantial variation in the methodological characteristics was observed for response rates (60–96%), ascertainment rates (53–99%), diagnostic tests and criteria used to diagnose type 2 diabetes.
Conclusions/interpretation
Worldwide incidence and prevalence of type 2 diabetes in children and adolescents vary substantially among countries, age categories and ethnic groups and this can be explained by variations in population characteristics and methodological dissimilarities between studies.
Background
Obesity and its related complications are increasing health issues. Since generally only minor weight loss is obtained with lifestyle intervention, additional pharmacological therapies ...such as metformin are often used.
Objective
We conducted a systematic review to provide an overview of the efficacy of ≥ 6 months of metformin treatment in children and adults with respect to weight, insulin resistance, and progression toward type 2 diabetes mellitus (T2DM).
Methods
In September 2018, we searched PubMed, Embase, and the Cochrane Library for studies published in English using the keywords metformin, obesity/overweight, and weight loss. Prospective studies reporting weight/body mass index (BMI) as a primary or secondary outcome in patients with overweight/obesity with ≥ 6 months’ metformin treatment were included. Included subjects were children and adults with overweight/obesity who received ≥ 6 months of metformin and/or lifestyle intervention, and/or placebo and/or lifestyle intervention, and/or standard care. Studies were independently screened by two reviewers. Data were extracted by one and verified by the other reviewer, and both reviewers assessed the risk of bias using the Cochrane risk-of-bias tool.
Results
Our review includes 15 pediatric and 14 adult studies. In children, after 6 months, more than half the studies reported a greater reduction in BMI with metformin versus controls. Only six studies had an intervention of > 6 months, and these studies found no further improvement in BMI in the metformin users, though their BMI was lower than that of controls. Three studies showed a significant improvement in insulin sensitivity in the metformin versus the control group. Adults using metformin experienced and maintained small decreases in weight irrespective of duration of intervention. In 11 of 14 studies, a greater reduction in weight/BMI was observed with metformin than with placebo. Progression toward T2DM was significantly reduced in adults using metformin, ranging from 7 to 31%. The safety and tolerability of metformin, withdrawal of participants, and comparison with other drugs were not taken into account.
Conclusions
The effects of metformin on weight/BMI vary, with smaller reductions in children than in adults. This could be because of differences in adherence, daily dosage, and insulin status. Metformin significantly reduced the progression toward T2DM in adults. Therefore, metformin should be considered as a treatment for obesity and its related complications.
Purpose
In this study we aimed (1) to identify the most prevalent physical symptoms and functional limitations that limit physical activity of patients with palliative treatment for metastatic breast ...cancer (MBC) and (2) to identify their preferences for exercise-based physical therapy programs, as a first step towards the development of physical therapist (PT)-guided exercise programs for patients with MBC.
Methods
We performed a mixed-method study that comprised a cross-sectional survey and two focus group sessions among patients with MBC. Survey results were analyzed using descriptive statistics. The focus groups were audio-taped, transcribed verbatim, and analyzed independently by two researchers, using directed content analysis.
Results
A total of 114 women (response rate 61%) completed the survey (mean age 63.5, SD 10.2). Eighty-six percent of the women reported at least some level of physical problems limiting their ability to be physically active, of whom 46% reported substantial problems. The most prevalent problems were fatigue, painful joints, painful muscles, and shortness of breath. Uptake of exercise appeared to be limited. Exercise preferences varied strongly. Fifty-three percent indicated a preference for some form of PT-supervision, and 34% for a prolonged period of time (> 8 weeks). Focus group results clarified that patients’ preferences for supervision, by PTs with special qualifications in oncology, were related to feelings of insecurity about their ability to self-manage physical functioning.
Conclusions
Patients with MBC experience a broad range of physical health problems that limit their ability to be physically active. While preferences vary strongly, patients with MBC would value the availability of high quality, PT-guided, tailored exercise programs.
Purpose
To evaluate the feasibility and outcomes of a tailored, goal-directed, and exercise-based physical therapy program for patients with metastatic breast cancer (MBC).
Methods
This was an ...observational, uncontrolled feasibility study. The physical therapy intervention was highly tailored to the individual patient’s goals, abilities, and preferences and could include functional, strength, aerobic, and relaxation exercises. Feasibility outcomes were participation rate (expected: 25%), safety, and adherence (percentage of attended sessions relative to scheduled sessions). Additional outcomes were goal attainment, self-reported physical functioning, fatigue, health-related quality of life, and patient and physical therapist satisfaction with the program.
Results
Fifty-five patients (estimated participation rate: 34%) were enrolled. Three patients did not start the intervention due to early disease progression. An additional 22 patients discontinued the program prematurely, mainly due to disease progression. Median intervention adherence was 90% and no major intervention-related adverse events occurred. A goal attainment score was available for 42 patients (of whom 29 had completed the program and 13 had prematurely dropped out). Twenty-two (52%) of these patients achieved their main goal fully or largely and an additional 15 patients (36%) partially. Eighty-five percent would “definitely recommend” the program to other patients with MBC. We observed a modest improvement in patient satisfaction with physical activities (Cohen’s
d
z
0.33).
Conclusion
The tailored intervention program was feasible in terms of uptake, safety, and outcomes and was highly valued by patients and physical therapists. However, disease progression interfered with the program, leading to substantial dropout.
Trial registration
NTR register: NTR6475
The contribution of genetic predisposing factors to the development of pediatric acute lymphoblastic leukemia (ALL), the most frequently diagnosed cancer in childhood, has not been fully elucidated. ...Children presenting with multiple de novo leukemias are more likely to suffer from genetic predisposition. Here, we selected five of these patients and analyzed the mutational spectrum of normal and malignant tissues. In two patients, we identified germline mutations in TYK2, a member of the JAK tyrosine kinase family. These mutations were located in two adjacent codons of the pseudokinase domain (p.Pro760Leu and p.Gly761Val). In silico modeling revealed that both mutations affect the conformation of this autoregulatory domain. Consistent with this notion, both germline mutations promote TYK2 autophosphorylation and activate downstream STAT family members, which could be blocked with the JAK kinase inhibitor I. These data indicate that germline activating TYK2 mutations predispose to the development of ALL.
Polypharmacy is common among patients with a limited life expectancy, even shortly before death. This is partly inevitable, because these patients often have multiple symptoms which need to be ...alleviated. However, the use of potentially inappropriate medications (PIMs) in these patients is also common. Although patients and relatives are often willing to deprescribe medication, physicians are sometimes reluctant due to the lack of evidence on appropriate medication management for patients in the last phase of life. The aim of the AMUSE study is to investigate whether the use of CDSS-OPTIMED, a software program that gives weekly personalized medication recommendations to attending physicians of patients with a limited life expectancy, improves patients' quality of life.
A multicentre stepped-wedge cluster randomized controlled trial will be conducted among patients with a life expectancy of three months or less. The stepped-wedge cluster design, where the clusters are the different study sites, involves sequential crossover of clusters from control to intervention until all clusters are exposed. In total, seven sites (4 hospitals, 2 general practices and 1 hospice from the Netherlands) will participate in this study. During the control period, patients will receive 'care as usual'. During the intervention period, CDSS-OPTIMED will be activated. CDSS-OPTIMED is a validated software program that analyses the use of medication based on a specific set of clinical rules for patients with a limited life expectancy. The software program will provide the attending physicians with weekly personalized medication recommendations. The primary outcome of this study is patients' quality of life two weeks after baseline assessment as measured by the EORTC QLQ-C15-PAL questionnaire, quality of life question.
This will be the first study investigating the effect of weekly personalized medication recommendations to attending physicians on the quality of life of patients with a limited life expectancy. We hypothesize that the CDSS-OPTIMED intervention could lead to improved quality of life in patients with a life expectancy of three months or less.
This trial is registered at ClinicalTrials.gov (NCT05351281, Registration Date: April 11, 2022).
Background. In view of the alarming incidence of obesity in children, insight into the epidemiology of the prediabetic state insulin resistance (IR) seems important. Therefore, the aim of this ...systematic review was to give an overview of all population-based studies reporting on the prevalence and incidence rates of IR in childhood. Methods. PubMed, Embase, and Cochrane library were searched in order to find all available population-based studies describing the epidemiology of IR in pediatric populations. Prevalence rates together with methods and cut-off values used to determine IR were extracted and summarized with weight and sex specific prevalence rates of IR if available. Results. Eighteen population-based studies were identified, describing prevalence rates varying between 3.1 and 44%, partly explained by different definitions for IR. Overweight and obese children had higher prevalence rates than normal weight children. In seven out of thirteen studies reporting sex specific results, girls seemed to be more affected than boys. Conclusion. Prevalence rates of IR reported in children vary widely which is partly due to the variety of definitions used. Overweight and obese children had higher prevalence and girls were more insulin resistant than boys. Consensus on the definition for IR in children is needed to allow for comparisons between different studies.
As a result of the rising prevalence of childhood obesity, there is an increasing interest in the type 2 diabetes mellitus precursor insulin resistance (IR). The aim of this study is to review ...definitions (methods and cutoff values) to define IR in children and to apply these definitions to a previously described obese pediatric population.
A systematic literature review on prevalence and/or incidence rates in children was performed. The extracted definitions were applied to an obese pediatric population.
In the 103 identified articles, 146 IR definitions were reported based on 14 different methods. Fasted definitions were used 137 times, whereas oral/intravenous glucose tolerance test-derived methods were used nine times. The homeostasis model for the assessment of insulin resistance (HOMA-IR) and fasted plasma insulin (FPI) were the most frequently used fasted methods (83 and 37 times, respectively). A wide range in cutoff values to define IR was observed, resulting in prevalence rates in the predefined obese pediatric population between 5.5% (FPI>30 mU/L) and 72.3% (insulin sensitivity indexMatsuda≤7.2).
To compare IR incidence and prevalence rates in pediatric populations, a uniform definition of IR should be defined.
This communication presents a compact leaky-wave antenna providing circular polarization from a dual-mode hollow waveguide (WG). The monolithic structure is based on a rectangular metallic guide that ...is perforated with crossed slots. The antenna is fed by a standard WR42 port, which is connected to the leaky WG by a transition that allows for dual-mode excitation. The axial ratio (AR) is determined by the size of the WG section and the dimensions of the crosses. In order to preserve the polarization purity, the geometry of the first radiating elements is modulated. Designed at <inline-formula> <tex-math notation="LaTeX">K </tex-math></inline-formula>-band, the present proposal is suitable for space applications since it relies on a full-metal structure. A design methodology is proposed based on the dual-mode dispersion analysis. Selective laser melting is used to monolithically 3-D print the antenna. Measurements are in good agreement with simulations and the AR is 0.92 dB at 20.5 GHz.
Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 ...month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed.
After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR.
Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6 to +1.4)).
While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
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