Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation

Background: Trends over time and possible socio-spatial inequalities in the incidence and care of type 1 diabetes mellitus (T1D) in children and adolescents are important parameters for the planning of target-specific treatment structures. Methodology: The incidence and prevalence of type 1 diabetes, diabetic ketoacidosis and severe hypoglycaemia as well as the HbA1c value are presented for under 18-year-olds based on data from the nationwide Diabetes Prospective Follow-up Registry (DPV) and the diabetes registry of North Rhine-Westphalia. Indicators were mapped by sex over time between 2014 and 2020, and stratified by sex, age and regional socioeconomic deprivation for 2020. Results: In 2020, the incidence was 29.2 per 100,000 person-years and the prevalence was 235.5 per 100,000 persons, with the figures being higher in boys than in girls in either case. The median HbA1c value was 7.5%. Ketoacidosis manifested in 3.4% of treated children and adolescents, significantly more often in regions with very high (4.5%) deprivation than in regions with very low deprivation (2.4%). The proportion of severe hypoglycaemia cases was 3.0%. Between 2014 and 2020, the incidence, prevalence and HbA1c levels changed little, while the proportions of ketoacidosis and severe hypoglycaemia decreased. Conclusions: The decrease in acute complications indicates that type 1 diabetes care has improved. Similar to previous studies, the results suggest an inequality in care by regional socioeconomic situation

Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation

Background: Trends over time and possible socio-spatial inequalities in the incidence and care of type 1 diabetes mellitus (T1D) in children and adolescents are important parameters for the planning of target-specific treatment structures. Methodology: The incidence and prevalence of type 1 diabetes, diabetic ketoacidosis and severe hypoglycaemia as well as the HbA1c value are presented for under 18-year-olds based on data from the nationwide Diabetes Prospective Follow-up Registry (DPV) and the diabetes registry of North Rhine-Westphalia. Indicators were mapped by sex over time between 2014 and 2020, and stratified by sex, age and regional socioeconomic deprivation for 2020. Results: In 2020, the incidence was 29.2 per 100,000 person-years and the prevalence was 235.5 per 100,000 persons, with the figures being higher in boys than in girls in either case. The median HbA1c value was 7.5%. Ketoacidosis manifested in 3.4% of treated children and adolescents, significantly more often in regions with very high (4.5%) deprivation than in regions with very low deprivation (2.4%). The proportion of severe hypoglycaemia cases was 3.0%. Between 2014 and 2020, the incidence, prevalence and HbA1c levels changed little, while the proportions of ketoacidosis and severe hypoglycaemia decreased. Conclusions: The decrease in acute complications indicates that type 1 diabetes care has improved. Similar to previous studies, the results suggest an inequality in care by regional socioeconomic situation

Inzidenz, Prävalenz und Versorgung von Typ-1-Diabetes bei Kindern und Jugendlichen in Deutschland: Zeittrends und sozialräumliche Lage

Hintergrund: Zeitliche Trends und mögliche sozialräumliche Ungleichheiten hinsichtlich der Häufigkeit und Versorgung von Typ-1-Diabetes mellitus (T1D) bei Kindern und Jugendlichen sind für die Planung von zielgerechten Behandlungsstrukturen von Bedeutung. Methode: Mit Daten der bundesweiten Diabetes-Patienten-Verlaufsdokumentation (DPV) und des Diabetesregisters in Nordrhein-Westfalen wurden für unter 18-Jährige Inzidenz und Prävalenz des Typ-1-Diabetes sowie HbA1c-Wert, diabetische Ketoazidosen und schwere Hypoglykämien dargestellt. Die Indikatoren wurden im Verlauf zwischen 2014 und 2020 nach Geschlecht und für 2020 stratifiziert nach Geschlecht, Alter und regionaler sozioökonomischer Deprivation abgebildet. Ergebnisse: 2020 betrug die Inzidenz 29,2 pro 100.000 Personenjahre und die Prävalenz 235,5 pro 100.000 Personen, mit jeweils höheren Werten bei Jungen als bei Mädchen. Der HbA1c-Wert betrug im Median 7,5 %. Bei 3,4 % der Behandelten trat eine Ketoazidose auf, signifikant häufiger in Regionen mit sehr hoher (4,5 %) als in Regionen mit sehr niedriger Deprivation (2,4 %). Der Anteil schwerer Hypoglykämien lag bei 3,0 %. Zwischen 2014 und 2020 änderten sich Inzidenz, Prävalenz und HbA1c-Wert kaum, während die Anteile von Ketoazidosen und schweren Hypoglykämien abnahmen. Schlussfolgerungen: Die Abnahme von Akutkomplikationen weist auf eine verbesserte Versorgung des Typ-1-Diabetes hin. Ähnlich wie in früheren Studien deuten die Ergebnisse eine Ungleichheit in der Versorgung nach sozialräumlicher Lage an

Inzidenz, Prävalenz und Versorgung von Typ-1-Diabetes bei Kindern und Jugendlichen in Deutschland: Zeittrends und sozialräumliche Lage

Hintergrund: Zeitliche Trends und mögliche sozialräumliche Ungleichheiten hinsichtlich der Häufigkeit und Versorgung von Typ-1-Diabetes mellitus (T1D) bei Kindern und Jugendlichen sind für die Planung von zielgerechten Behandlungsstrukturen von Bedeutung. Methode: Mit Daten der bundesweiten Diabetes-Patienten-Verlaufsdokumentation (DPV) und des Diabetesregisters in Nordrhein-Westfalen wurden für unter 18-Jährige Inzidenz und Prävalenz des Typ-1-Diabetes sowie HbA1c-Wert, diabetische Ketoazidosen und schwere Hypoglykämien dargestellt. Die Indikatoren wurden im Verlauf zwischen 2014 und 2020 nach Geschlecht und für 2020 stratifiziert nach Geschlecht, Alter und regionaler sozioökonomischer Deprivation abgebildet. Ergebnisse: 2020 betrug die Inzidenz 29,2 pro 100.000 Personenjahre und die Prävalenz 235,5 pro 100.000 Personen, mit jeweils höheren Werten bei Jungen als bei Mädchen. Der HbA1c-Wert betrug im Median 7,5 %. Bei 3,4 % der Behandelten trat eine Ketoazidose auf, signifikant häufiger in Regionen mit sehr hoher (4,5 %) als in Regionen mit sehr niedriger Deprivation (2,4 %). Der Anteil schwerer Hypoglykämien lag bei 3,0 %. Zwischen 2014 und 2020 änderten sich Inzidenz, Prävalenz und HbA1c-Wert kaum, während die Anteile von Ketoazidosen und schweren Hypoglykämien abnahmen. Schlussfolgerungen: Die Abnahme von Akutkomplikationen weist auf eine verbesserte Versorgung des Typ-1-Diabetes hin. Ähnlich wie in früheren Studien deuten die Ergebnisse eine Ungleichheit in der Versorgung nach sozialräumlicher Lage an

A Multi-Institutional Analysis of Prostate Cancer Patients With or Without 68Ga-PSMA PET/CT Prior to Salvage Radiotherapy of the Prostatic Fossa

Introduction: 68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only. Material and Methods: This retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters. Results: Median follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= <0.001), Gleason score (GS ≤ 7 vs. GS8-10; p=0.003), pre-sRT PSA (<0.5 vs. ≥0.5ng/ml; p<0.001) and sRT dose (<70 vs. ≥70Gy; p<0.001) were the only factors significantly associated with improved BRFS. This was not seen for the use of 68Ga-PSMA PET/CT prior to sRT (p=0.789). Matched-pair analysis consisted of 95 pairs of PCa patients with or without PET/CT and no significant difference in BRFS based on the use of PET/CT was evident (p=0.884). Conclusion: This analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best “diagnostic window” for 68Ga-PSMA PET/CT

Chromosomal radiosensitivity and acute radiation side effects after radiotherapy in tumour patients - a follow-up study

Radiotherapists are highly interested in optimizing doses especially for patients who tend to suffer from side effects of radiotherapy (RT). It seems to be helpful to identify radiosensitive individuals before RT. Thus we examined aberrations in FISH painted chromosomes in in vitro irradiated blood samples of a group of patients suffering from breast cancer. In parallel, a follow-up of side effects in these patients was registered and compared to detected chromosome aberrations. METHODS: Blood samples (taken before radiotherapy) were irradiated in vitro with 3 Gy X-rays and analysed by FISH-painting to obtain aberration frequencies of first cycle metaphases for each patient. Aberration frequencies were analysed statistically to identify individuals with an elevated or reduced radiation response. Clinical data of patients have been recorded in parallel to gain knowledge on acute side effects of radiotherapy. RESULTS: Eight patients with a significantly elevated or reduced aberration yield were identified by use of a t-test criterion. A comparison with clinical side effects revealed that among patients with elevated aberration yields one exhibited a higher degree of acute toxicity and two patients a premature onset of skin reaction already after a cumulative dose of only 10 Gy. A significant relationship existed between translocations in vitro and the time dependent occurrence of side effects of the skin during the therapy period. CONCLUSIONS: The results suggest that translocations can be used as a test to identify individuals with a potentially elevated radiosensitivity

Quinolizidine alkaloid biosynthesis in lupins and prospects for grain quality improvement

Quinolizidine alkaloids (QAs) are toxic secondary metabolites found within the genus Lupinus, some species of which are commercially important grain legume crops including Lupinus angustifolius (narrow-leafed lupin, NLL), L. luteus (yellow lupin), L. albus (white lupin), and L. mutabilis (pearl lupin), with NLL grain being the most largely produced of the four species in Australia and worldwide. While QAs offer the plants protection against insect pests, the accumulation of QAs in lupin grain complicates its use for food purposes as QA levels must remain below the industry threshold (0.02%), which is often exceeded. It is not well understood what factors cause grain QA levels to exceed this threshold. Much of the early work on QA biosynthesis began in the 1970– 1980s, with many QA chemical structures well-characterized and lupin cell cultures and enzyme assays employed to identify some biosynthetic enzymes and pathway intermediates. More recently, two genes associated with these enzymes have been characterized, however, the QA biosynthetic pathway remains only partially elucidated. Here, we review the research accomplished thus far concerning QAs in lupin and consider some possibilities for further elucidation and manipulation of the QA pathway in lupin crops, drawing on examples from model alkaloid species. One breeding strategy for lupin is to produce plants with high QAs in vegetative tissues while low in the grain in order to confer insect resistance to plants while keeping grain QA levels within industry regulations. With the knowledge achieved on alkaloid biosynthesis in other plant species in recent years, and the recent development of genomic and transcriptomic resources for NLL, there is considerable scope to facilitate advances in our knowledge of QAs, leading to the production of improved lupin crops. © 2017 Frick, Kamphuis, Siddique, Singh and Foley

Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

<p>Abstract</p> <p>Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical implementation. A potential chemotherapy indication might exist as palliative option for patients who have progressive disease after radiotherapy.</p

Chromosomal radiosensitivity and acute radiation side effects after radiotherapy in tumour patients - a follow-up study

Abstract Background Radiotherapists are highly interested in optimizing doses especially for patients who tend to suffer from side effects of radiotherapy (RT). It seems to be helpful to identify radiosensitive individuals before RT. Thus we examined aberrations in FISH painted chromosomes in in vitro irradiated blood samples of a group of patients suffering from breast cancer. In parallel, a follow-up of side effects in these patients was registered and compared to detected chromosome aberrations. Methods Blood samples (taken before radiotherapy) were irradiated in vitro with 3 Gy X-rays and analysed by FISH-painting to obtain aberration frequencies of first cycle metaphases for each patient. Aberration frequencies were analysed statistically to identify individuals with an elevated or reduced radiation response. Clinical data of patients have been recorded in parallel to gain knowledge on acute side effects of radiotherapy. Results Eight patients with a significantly elevated or reduced aberration yield were identified by use of a t-test criterion. A comparison with clinical side effects revealed that among patients with elevated aberration yields one exhibited a higher degree of acute toxicity and two patients a premature onset of skin reaction already after a cumulative dose of only 10 Gy. A significant relationship existed between translocations in vitro and the time dependent occurrence of side effects of the skin during the therapy period. Conclusions The results suggest that translocations can be used as a test to identify individuals with a potentially elevated radiosensitivity.</p