KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with ...excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients.
In this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817.
90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3–10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA1c and sulfonylurea at all time points (ie, pre-transfer for HbA1c, year 1, and most recent follow-up; n=64)—median HbA1c was 8·1% (IQR 7·2–9·2; 65·0 mmol/mol 55·2–77·1) before transfer to sulfonylureas, 5·9% (5·4–6·5; 41·0 mmol/mol 35·5–47·5; p<0·0001 vs pre-transfer) at 1 year, and 6·4% (5·9–7·3; 46·4 mmol/mol 41·0–56·3; p<0·0001 vs year 1) at most recent follow-up (median 10·3 years IQR 9·2–10·9). In the same patients, median sulfonylurea dose at 1 year was 0·30 mg/kg per day (0·14–0·53) and at most recent follow-up visit was 0·23 mg/kg per day (0·12–0·41; p=0·03). No reports of severe hypoglycaemia were recorded in 809 patient-years of follow-up for the whole cohort (n=81). 11 (14%) patients reported mild, transient side-effects, but did not need to stop sulfonylurea therapy. Seven (9%) patients had microvascular complications; these patients had been taking insulin longer than those without complications (median age at transfer to sulfonylureas 20·5 years IQR 10·5–24·0 vs 4·1 years 1·3–10·2; p=0·0005). Initial improvement was noted following transfer to sulfonylureas in 18 (47%) of 38 patients with CNS features. After long-term therapy with sulfonylureas, CNS features were seen in 52 (64%) of 81 patients.
High-dose sulfonylurea therapy is an appropriate treatment for patients with KCNJ11 permanent neonatal diabetes from diagnosis. This therapy is safe and highly effective, maintaining excellent glycaemic control for at least 10 years.
Wellcome Trust, Diabetes UK, Royal Society, European Research Council, Norwegian Research Council, Kristian Gerhard Jebsen Foundation, Western Norway Regional Health Authority, Southern and Eastern Norway Regional Health Authority, Italian Ministry of Health, Aide aux Jeunes Diabetiques, Societe Francophone du Diabete, Ipsen, Slovak Research and Development Agency, and Research and Development Operational Programme funded by the European Regional Development Fund.
Clinical reasoning, comprising the processes of clinical thinking, which form the basis of medical decisions, constitutes a central competence in the clinical routine on which diagnostic and ...therapeutic steps are based. In medical curricula in Germany, clinical reasoning is currently taught explicitly only to a small extend. Therefore, the aim of this project was to develop and implement a clinical reasoning course in the final year of undergraduate medical training.
A clinical reasoning course with six learning units and 18 learning objectives was developed, which was taught by two to four instructors on the basis of 32 paper cases from the clinical practice of the instructors. In the years 2011 to 2013, the course of eight weeks with two hours per week was taught seven times. Before the first and after the last seminar, the participating students filled out a self-assessment questionnaire with a 6-point Likert scale regarding eight different clinical reasoning skills. At the same times, they received a patient case with the assignment to prepare a case presentation and differential diagnoses.
From 128 participating students altogether, 42 complete data sets were available. After the course, participants assessed themselves significantly better than before the course in all eight clinical reasoning skills, for example in "Summarizing and presentation of a paper case" or in the "Skill to enumerate differential diagnoses" (p<0.05). The greatest increase occurred in the skill to recognize typical cognitive errors in medicine and to identify risk situations for their occurrence (pre: 2.98±0.92 and retro-pre: 2.64±1.01, respectively, versus post: 4.38±0.88). Based on the ratio of number of words used per keywords used the problem presentation of the paper case was significantly more focused after the course (p=0.011). A significant increase in the number of gathered differential diagnoses was not detected after the course.
The newly developed and established Clinical Reasoning Course leads to a gain in the desired skills from the students' self-assessment perspective and to a more structured case presentation. To establish better options to exercise clinical reasoning, a longitudinal implementation in the medical curriculum seems to be desirable. Faculty training would be useful to implement the concept as standardized as possible.
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Es wurden vielmehr die konsensbasierten Leitlinien der European Society of Cardiology (ESC) übernommen, obgleich bei ihnen ein hoher Überarbeitungsbedarf hinsichtlich Transparenz und Methodik besteht ...1. AGREE Next Steps Consortium (2009) Appraisal of Guidelines for Research & Evaluation II – AGREE II: Do statins reduce the risk of myocardial infarction in patients with heart failure? A pooled individual-level reanalysis of CORONA and GISSI-HF.
The regulation of the activity of the approximately 30 pS nonselective cation channel (NSC channel) was studied by the patch-clamp technique in inside-out patches obtained from rat brown-fat cells. ...NSC channel activity was induced by excision; reduced redox state induced by dithiothreitol accelerated the kinetics in the excised state. The NSC channels were inhibited by the fenamates flufenamic acid and mefenamic acid but not by NS-1619 or SKF-96365. The channels were inhibited by purine nucleotides but not by polyamines. No evidence for protein kinase C, CaM kinase or protein kinase A activation of the NSC channel was obtained. NSC-channel activity was stimulated in a concentration-dependent manner by Ca2+ but the EC50 was very high (0.81 mM), in comparison to expected cytosolic Ca2+ levels. In the presence of ATP, even higher Ca2+ levels were necessary for comparable NSC-channel activation. The increase in Po was not associated with an increase in open-time constants. We conclude that although high Ca2+ levels can experimentally activate the NSC channel, a further mediatory step must probably be postulated in order to link alpha1-adrenergic stimulation to NSC-channel activation.
Peri‐implant diseases Klinge, Björn; Klinge, Anna; Bertl, Kristina ...
European journal of oral sciences,
October 2018, Volume:
126, Issue:
S1
Journal Article
Peer reviewed
Open access
When celebrating 100 yr of dental research in the Nordic dental research community (i.e. Nordisk Odontologisk Förening (NOF)), it is relevant to include dental implant treatment. In essence, the ...successful progress of implant treatment has added both to the quality of life for patients and also to many aspects of professional development and job satisfaction for dentists. When appreciating the success story it also seems relevant to highlight some of the problems related to this treatment. Both technical and biological complications have often been ignored when reporting long‐term results following implant treatment. Different opinions have been expressed in relation to the etiology of peri‐implant diseases. Some even choose to ignore this condition as a clinical problem. This article presents a short overview of peri‐implant diseases (i.e. peri‐implant mucositis and peri‐implantitis). The lack of internationally agreed disease definitions for peri‐implant diseases, as with periodontitis, results in wide variation of estimates for the occurrence of peri‐implant diseases when epidemiological data are reported. The profession still strives to find and define the best way to deal with peri‐implant diseases once they are accurately diagnosed. Awareness of the tissue conditions in the peri‐implant area, and relevant action when indicated, seems to be critical for the continued long‐term successful outcome of dental implant treatment.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives
A considerable portion of the adult population has received and/or is receiving treatment with antiresorptive drugs (ARDs). It is thus relevant to assess possible side effects of ARD ...intake in connection to various aspects of implant therapy. The aim of this study was to answer the focused question “In patients with systemic intake of ARDs, what is the outcome and complication rate of implant therapy including associated bone grafting procedures comparing to patients without systemic intake of ARDs?”
Materials and Methods
Original studies fulfilled predefined inclusion criteria (e.g., case series, cohort studies, case–control studies, and controlled and/or randomized controlled clinical trials; retro‐ or prospective design; and ≥10 patients with systemic intake of ARDs). Various patient‐, medication‐, and intervention‐related parameters i.e., implant loss, grafting procedure complication/failure, peri‐implant marginal bone levels/loss, medication‐related osteonecrosis of the jaws (MRONJ), and peri‐implantitis were extracted, and meta‐analyses and quality assessment were performed.
Results
Twenty‐four studies with bisphosphonate (BP) intake (mainly low dose for osteoporosis treatment) and seven studies on hormone replacement therapy (HRT), including ≥10 patients, and controls not taking the medication were identified. Furthermore, seven studies on MRONJ associated with implants were included. Meta‐analyses based on four studies reporting on patient level and eight studies reporting on implant level showed no significant differences in terms of implant loss between patients on BPs (mainly low dose for osteoporosis treatment) and controls. Furthermore, low‐dose BP intake did not compromise peri‐implant marginal bone levels. Based on two studies, no negative effect of HRT was observed on the implant level, while HRT appeared to exert a marginally significant negative effect regarding implant survival on the patient level and regarding peri‐implant marginal bone levels. Based on six studies reporting single‐patient data, MRONJ in patients on BP for osteoporosis appeared in 70% of the cases >36 months after start of drug intake, while in patients with cancer, MRONJ appeared in 64% of the cases ≤36 months after first BP intake.
Conclusion
Low‐dose oral BP intake for osteoporosis treatment, in general, does not compromise implant therapy, that is, patients on ARDs do not lose more implants nor get more implant‐related complications/failures comparing to implant patients without BP intake. There is almost no information available on the possible effect on implant therapy of high‐dose BPs or other widely used ARDs (e.g., denosumab), or on the success or safety of bone grafting procedures. Patients with high‐dose ARD intake for management of malignancies, patients on oral BP over a longer period of time, and patients with comorbidities should be considered as high‐risk patients for MRONJ.
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