Pregnancy following kidney transplantation - impact on mother and graft function and focus on childrens’ longitudinal development

BACKGROUND: Pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications. After careful patient selection successful pregnancies are described. Little is known about fetal outcomes and data is particularly scarce on childrens´ early development up to two years when born to kidney/-pancreas transplant recipients. Here, we analyzed maternal and fetal risk and evaluated graft function during pregnancy in transplanted women. We aimed to identify factors affecting the outcomes of mothers and their grafts during pregnancy and of children up to 2 years after delivery/ birth. METHODS: All consecutive pregnancies in kidney/ kidney-pancreas recipients with live-born children from 2002 to 2016 were evaluated in two transplant centers (Charité Berlin/ University Tuebingen). All data was gathered from medical records. Impact of pregnancy on obstetrical risks, graft function and fetal development was evaluated. Additionally, for the first time development of children, including physical examination and assessment of neurological function were evaluated at 12 and 24 months. RESULTS: Thirty-two pregnancies in 28 patients with a median duration of 34 gestational weeks (range, 24-38) were analyzed. 13 patients (46.4%) developed deterioration of kidney graft function > 10 ml/min during pregnancy. In majority, caesarean section was performed (75%). Twenty-five (78.1%) children were born prematurely, thereof (16%) < 28 weeks. Almost 70% had low birth weights (LBW) (< 2.500 g); median birth weight was 2.030 g. General health and physical constitution of children were unremarkable with normal development in 94% at 12 and 24 months of corrected age, respectively. CONCLUSION: Despite the high rate of preterm birth and LBW, development up to two years was age-appropriate in this cohort. Due to low absolute numbers, increasing efforts in centralized counseling, diagnostics and committed specialist support are required. Decisive treatment of these high-risk patients in specialized units leading to better performance of these patients (mother/ fetus) is deemed superior. In order to confirm this, prospective studies on neonatal and pediatric outcomes with a standard-of-care comparator arm will be conducted

I can do this! : Coping der Health Professionals in der Palliative Care

Einleitung: Eine älter werdende Population mit zunehmend von chronischen und degenerativen Krankheiten Betroffenen führt dazu, dass das Bedürfnis nach Palliative Care steigt. Interprofessionelle Teams in diesem Setting sind mit steigenden fachlichen Anforderungen bei komplexer werden Patient:innen-/Familien-Situationen sowie psychischem und sozialem Stress im Team oder im Privatleben konfrontiert. Die Personalknappheit im Gesundheitswesen verstärkt diese Belastung, welche zu Erschöpfungszuständen bis hin zu einem Burnout führen kann. Die Literatur zeigt, dass Betroffene durch das Anwenden von Coping-Strategien sowie soziale Unterstützung besser mit Belastungen im Palliative Care-Setting umgehen können. Unter Coping wird die «Handlung einer Person, die darauf abzielt, eine belastende Situation zu bewältigen” verstanden. Ziel des Posters ist es, Strategien aufzuzeigen, welche Health Professionals im Palliative Care-Setting anwenden können, um besser mit den auftretenden Belastungen umgehen zu können. Methode: Es wurde eine systematisierte Literaturrecherche auf den Datenbanken CINAHL Complete und PubMed vorgenommen. Mittels Citation Tracking wurde zusätzliche Literatur eingeschlossen. Ergebnisse: Die dargestellten Ergebnisse basieren auf vier relevanten Studien. Es konnten zwei Ergebnis-Hauptkategorien gebildet werden: (1) Coping-Strategien der Health Professionals, welche aus eigenem Antrieb angewendet werden können, und (2) institutionelle Strategien, welche sich auf Angebote der Institution beziehen, und die Health Professionals bei ihrem Coping unterstützen. Die zwei Kategorien dienen gemeinsam der Bewältigung von Stress in der Palliative Care. (1) Coping-Strategien der Health Professionals: Selbstfürsorge, Sinnhaftigkeit im Berufsleben, Achtsamkeit, Seine eigenen Grenzen kennen, Gefühle äussern, Vertrauensverhältnis zu Angehörigen, Peer-Austausch. (2) Institutionelle Strategien: Interprofessioneller Austausch, Fallbesprechung, Nachbesprechung und Aufarbeitung, Fachspezifische Weiterbildung Diskussion: Zur Reduktion der Belastungen von Health Professionals im Palliative Care-Setting können einerseits Coping-Strategien der Professionals selbst, andererseits institutionelle Strategien wirksam sein. Es besteht dabei eine Wechselwirkung zwischen dem selbst initiierten, persönlichen Coping und den institutionellen Strategien. Ziel der Health Professionals sollte das Auffinden bzw. Beibehalten einer persönlichen Balance durch Anwendung eigener Coping-Strategien sowie dem Nützen der institutionellen Strategien sein. Diese Balance wirkt sich positiv auf die Gesundheit der Health Professionals, aber auch auf die Betreuungsqualität der Patient:innen und Familien aus. Schlussfolgerung: Das Coping der Health Professionals im Palliative Care-Setting ist ein zentrales Thema, welches sich direkt auf die Gesundheit der Health Professinals selbst sowie auf die Betreuungsqualität von Patient:innen und Familien auswirken kann. Insbesondere auch die Schlüsselrolle der Institutionen sollte weiter erforscht werden

Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in children with type 1 diabetes

Hypoglycemia is the most common complication in insulin treated diabetes. Though mostly mild, it can be fatal in rare cases: It is hypothesized that hypoglycemia related QTc prolongation contributes to cardiac arrhythmia.; To evaluate influence of nocturnal hypoglycemia on QTc and heart rate variability (HRV) in children with T1D.; Children and adolescents with T1D for at least 6 months participated in an observational study using continuous glucose monitoring (CGM) and Holter electrocardiogram for five consecutive nights. Mean QTc was calculated for episodes of nocturnal hypoglycemia (<3.7 mmol/L) and compared to periods of the same duration preceding hypoglycemia. HRV (RMSSD, low and high frequency power LF and HF) was analyzed for different 15 min intervals: before hypoglycemia, onset of hypoglycemia, before/after nadir, end of hypoglycemia and after hypoglycemia.; Mean QTc during hypoglycemia was significantly longer compared to euglycemia (412 ± 15 vs. 405 ± 18 ms, p = 0.005). HRV changed significantly: RMSSD (from 88 ± 57 to 73 ± 43 ms) and HF (from 54 ± 17 to 47 ± 17nu) decreased from before hypoglycemia to after nadir, while heart rate (from 69 ± 9 to 72 ± 12 bpm) and LF (from 44 ± 17 to 52 ± 21 nu) increased (p = 0.04).; A QTc lengthening effect of nocturnal hypoglycemia in children with T1D was documented. HRV changes occurred even before detection of nocturnal hypoglycemia by CGM, which may be useful for hypoglycemia prediction

Fear of hypoglycemia and quality of life in young people with type 1 diabetes and their parents in the era of sensor glucose monitoring

IntroductionIt is crucial to understand psychosocial outcomes in children and adolescents with type 1 diabetes (T1D) and their families to provide optimal family-centered care. Hence, the aim of this study was to explore psychosocial outcomes in young people with T1D and their parents using currently available glucose monitoring devices in a real-life clinic setting.MethodsChildren and adolescents aged 2-18 years with T1D for more than 6 months and their parents were recruited into a cross-sectional study to complete the Hypoglycemia Fear Survey (HFS) and the Pediatric Quality of Life Inventory (PedsQL) Generic Score Scales, Diabetes Module and Family Impact Module. Demographics and diabetes-specific parameters were obtained from medicals records.ResultsFifty-nine children and adolescents (mean age 15.1 ± 3.0 years) and 49 parents of children (mean age of children 12.5± 3.3 years) of which 44 were child-parent dyads completed the questionnaires. Parents had a higher mean (SD) FOH total and worry subscore than children, total score was 37.9 (14.6) vs. 32.2 (11.9), p = 0.047 and worry subscore was 17.8 (10.4) vs. 12.8 (9.0), p = 0.01. Furthermore, lower parental diabetes-specific QoL score was observed in parents, 78.8 (12.2) vs. 82.7 (10.3), p=0.02. No difference in FOH and QoL between real-time continuous glucose monitoring (rtCGM) and intermittently scanned glucose monitoring (isCGM) users and users of devices with and without alerts was observed. In isCGM users (n=36 completing the child questionnaires, n=33 completing parent questionnaires), higher parental FOH and lower parental diabetes-specific QoL correlated with higher scanning frequency, r = 0.399, p = 0.021, and r = -0.464, p = 0.007 respectively. No significant correlation was documented between scanning frequency and child questionnaire scores.ConclusionsParents are more likely to perceive higher levels of psychosocial burden related to their child’s diabetes than children and adolescents with T1D, especially parents of younger children. This highlights the need for family-based education and treatment resources to support parents in diabetes management in addition to rapidly advancing diabetes technology. In isCGM users, higher parental FOH and lower parent-perceived QoL correlated with a higher scanning frequency, indicating the potential impact of glucose monitoring modality on psychosocial outcomes or vice versa

Mild inborn errors of metabolism in commonly used inbred mouse strains.

Inbred mouse strains are a cornerstone of translational research but paradoxically many strains carry mild inborn errors of metabolism. For example, alpha-aminoadipic acidemia and branched-chain ketoacid dehydrogenase deficiency are known in C57BL/6J mice. Using RNA sequencing, we now reveal the causal variants in Dhtkd1 and Bckdhb, and the molecular mechanism underlying these metabolic defects. C57BL/6J mice have decreased Dhtkd1 mRNA expression due to a solitary long terminal repeat (LTR) in intron 4 of Dhtkd1. This LTR harbors an alternate splice donor site leading to a partial splicing defect and as a consequence decreased total and functional Dhtkd1 mRNA, decreased DHTKD1 protein and alpha-aminoadipic acidemia. Similarly, C57BL/6J mice have decreased Bckdhb mRNA expression due to an LTR retrotransposon in intron 1 of Bckdhb. This transposable element encodes an alternative exon 1 causing aberrant splicing, decreased total and functional Bckdhb mRNA and decreased BCKDHB protein. Using a targeted metabolomics screen, we also reveal elevated plasma C5-carnitine in 129 substrains. This biochemical phenotype resembles isovaleric acidemia and is caused by an exonic splice mutation in Ivd leading to partial skipping of exon 10 and IVD protein deficiency. In summary, this study identifies three causal variants underlying mild inborn errors of metabolism in commonly used inbred mouse strains

Lifestyle Intervention with or without Lay Volunteers to Prevent Type 2 Diabetes in People with Impaired Fasting Glucose and/or Nondiabetic Hyperglycemia:A Randomized Clinical Trial

Importance:  Nearly half of the older adult population has diabetes or a high-risk intermediate glycemic category, but we still lack trial evidence for effective type 2 diabetes prevention interventions in most of the current high-risk glycemic categories. Objective:  To determine whether a group-based lifestyle intervention (with or without trained volunteers with type 2 diabetes) reduced the risk of progression to type 2 diabetes in populations with a high-risk glycemic category. Design, Setting, and Participants: The Norfolk Diabetes Prevention Study was a parallel, 3-arm, group-based, randomized clinical trial conducted with up to 46 months of follow-up from August 2011 to January 2019 at 135 primary care practices and 8 intervention sites in the East of England. We identified 141 973 people at increased risk of type 2 diabetes, screened 12 778 (9.0%), and randomized those with a high-risk glycemic category, which was either an elevated fasting plasma glucose level alone (≥110 and <126 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) or an elevated glycated hemoglobin level (≥6.0% to <6.5%; nondiabetic hyperglycemia) with an elevated fasting plasma glucose level (≥100 to <110 mg/dL).Interventions A control arm receiving usual care (CON), a theory-based lifestyle intervention arm of 6 core and up to 15 maintenance sessions (INT), or the same intervention with support from diabetes prevention mentors, trained volunteers with type 2 diabetes (INT-DPM). Main Outcomes and Measures:  Type 2 diabetes incidence between arms.Results:  In this study, 1028 participants were randomized (INT, 424 [41.2%] [166 women (39.2%)]; INT-DPM, 426 [41.4%] [147 women (34.5%)]; CON, 178 [17.3%] [70 women (%39.3)]) between January 1, 2011, and February 24, 2017. The mean (SD) age was 65.3 (10.0) years, mean (SD) body mass index 31.2 (5) (calculated as weight in kilograms divided by height in meters squared), and mean (SD) follow-up 24.7 (13.4) months. A total of 156 participants progressed to type 2 diabetes, which comprised 39 of 171 receiving CON (22.8%), 55 of 403 receiving INT (13.7%), and 62 of 414 receiving INT-DPM (15.0%). There was no significant difference between the intervention arms in the primary outcome (odds ratio [OR], 1.14; 95% CI, 0.77-1.7; P = .51), but each intervention arm had significantly lower odds of type 2 diabetes (INT: OR, 0.54; 95% CI, 0.34-0.85; P = .01; INT-DPM: OR, 0.61; 95% CI, 0.39-0.96; P = .033; combined: OR, 0.57; 95% CI, 0.38-0.87; P = .01). The effect size was similar in all glycemic, age, and social deprivation groups, and intervention costs per participant were low at $153 (£122). Conclusions and Relevance:  The Norfolk Diabetes Prevention lifestyle intervention reduced the risk of type 2 diabetes in current high-risk glycemic categories. Enhancing the intervention with DPM did not further reduce diabetes risk. These translatable results are relevant for current diabetes prevention efforts

Healthcare recommendations for Joubert syndrome

Joubert syndrome (JS) is a recessive neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation recognizable on axial brain magnetic resonance imaging as the "Molar Tooth Sign". Although defined by the neurological features, JS is associated with clinical features affecting many other organ systems, particularly progressive involvement of the retina, kidney, and liver. JS is a rare condition; therefore, many affected individuals may not have easy access to subspecialty providers familiar with JS (e.g., geneticists, neurologists, developmental pediatricians, ophthalmologists, nephrologists, hepatologists, psychiatrists, therapists, and educators). Expert recommendations can enable practitioners of all types to provide quality care to individuals with JS and know when to refer for subspecialty care. This need will only increase as precision treatments targeting specific genetic causes of JS emerge. The goal of these recommendations is to provide a resource for general practitioners, subspecialists, and families to maximize the health of individuals with JS throughout the lifespan

Aktuelle Herausforderungen in der Therapie des Typ-1-Diabetes beim Kind

Das 1921 entdeckte Insulin wurde 1922 erstmals als Therapie für Typ-1-Diabetes eingeführt. Hundert Jahre später wird es immer noch als einzige medikamentöse Behandlung eingesetzt. Die jüngsten Fortschritte haben zu einer erheblichen Optimierung der Stoffwechselkontrolle beigetragen. Einleitung Typ-1-Diabetes (T1D) ist eine der häufigsten chronischen Erkrankungen bei Kindern, mit einer jährlichen Inzidenzzunahme von 3% [1]. Die Ätiologie des T1D ist unbekannt, aber eine Dysregulation der Autoimmunität, dokumentiert durch die Zirkulation von Autoantikörpern, sowie eine genetische Prädisposition sind ursächlich beteiligt. Das Risiko, an T1D zu erkranken, beträgt bei Kindern 0,4%; gibt es bereits an T1D-erkrankte Familienangehörige, steigt das Risiko um das Zehnfache. Neueste Daten weisen auf einen deutlichen Anstieg der weltweiten Inzidenz während der Corona-Pandemie hin [2–5]. Ziel dieses Beitrags ist es, die neuesten Entwicklungen und aktuellen Herausforderungen bei der Behandlung des T1D bei Kindern darzustellen

Integrating diabetes, hypertension and HIV care in sub-Saharan Africa: a Delphi consensus study on international best practice

Background: Although HIV continues to have a high prevalence among adults in sub-Saharan Africa (SSA), the burden of noncommunicable diseases (NCD) such as diabetes and hypertension is increasing rapidly. There is an urgent need to expand the capacity of healthcare systems in SSA to provide NCD services and scale up existing chronic care management pathways. The aim of this study was to identify key components, outcomes, and best practice in integrated service provision for the prevention, identification and treatment of HIV, hypertension and diabetes. Methods: An international, multi stakeholder e-Delphi consensus study was conducted over two successive rounds. In Round 1, 24 participants were asked to score 27 statements, under the headings ‘Service Provision’ and ‘Benefits of Integration’, by importance. In Round 2, the 16 participants who completed Round 1 were shown the distribution of scores from other participants along with the score that they attributed to an outcome and were asked to reflect on the score they gave, based on the scores of the other participants and then to rescore if they wished to. Nine participants completed Round 2. Results: Based on the Round 1 ranking, 19 of the 27 outcomes met the 70% threshold for consensus. Four additional outcomes suggested by participants in Round 1 were added to Round 2, and upon review by participants, 22 of the 31 outcomes met the consensus threshold. The five items participants scored from 7 to 9 in both rounds as essential for effective integrated healthcare delivery of health services for chronic conditions were improved data collection and surveillance of NCDs among people living with HIV to inform integrated NCD/HIV programme management, strengthened drug procurement systems, availability of equipment and access to relevant blood tests, health education for all chronic conditions, and enhanced continuity of care for patients with multimorbidity. Conclusions: This study highlights the outcomes which may form key components of future complex interventions to define a model of integrated healthcare delivery for diabetes, hypertension and HIV in sub-Saharan Africa

Effects of the Norfolk diabetes prevention lifestyle intervention (NDPS) on glycaemic control in screen-detected type 2 diabetes: a randomised controlled trial

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The dataset used in this publication is available from the corresponding author on reasonable request.Background The purpose of this trial was to test if the Norfolk Diabetes Prevention Study (NDPS) lifestyle intervention, recently shown to reduce the incidence of type 2 diabetes in high-risk groups, also improved glycaemic control in people with newly diagnosed screen-detected type 2 diabetes. Methods We screened 12,778 participants at high risk of type 2 diabetes using a fasting plasma glucose and glycosylated haemoglobin (HbA1c). People with screen-detected type 2 diabetes were randomised in a parallel, three-arm, controlled trial with up to 46 months of follow-up, with a control arm (CON), a group-based lifestyle intervention of 6 core and up to 15 maintenance sessions (INT), or the same intervention with additional support from volunteers with type 2 diabetes trained to co-deliver the lifestyle intervention (INT-DPM). The pre-specified primary end point was mean HbA1c compared between groups at 12 months. Results We randomised 432 participants (CON 149; INT 142; INT-DPM 141) with a mean (SD) age of 63.5 (10.0) years, body mass index (BMI) of 32.4 (6.4) kg/m2, and HbA1c of 52.5 (10.2) mmol/mol. The primary outcome of mean HbA1c at 12 months (CON 48.5 (9.1) mmol/mol, INT 46.5 (8.1) mmol/mol, and INT-DPM 45.6 (6.0) mmol/mol) was significantly lower in the INT-DPM arm compared to CON (adjusted difference −2.57 mmol/mol; 95% CI −4.5, −0.6; p = 0.007) but not significantly different between the INT-DPM and INT arms (−0.55 mmol/mol; 95% CI −2.46, 1.35; p = 0.57), or INT vs CON arms (−2.14 mmol/mol; 95% CI −4.33, 0.05; p = 0.07). Subgroup analyses showed the intervention had greater effect in participants  65 years old; p = 0.007). The use of oral hypoglycaemic medication was associated with a significantly lower mean HbA1c but only within the INT-DPM arm compared to CON (−7.0 mmol/mol; 95% CI −11.5, −2.5; p = 0.003). Conclusion The NDPS lifestyle intervention significantly improved glycaemic control after 12 months in people with screen-detected type 2 diabetes when supported by trained peer mentors with type 2 diabetes, particularly those receiving oral hypoglycaemics and those under 65 years old. The effect size was modest, however, and not sustained at 24 months. Trial registration ISRCTN34805606. Retrospectively registered 14.4.16National Institute for Health Research (NIHR