Ideal bad news delivery requires skilled communication and team support. The literature has primarily focused on patient preferences, impact on care decisions, healthcare roles, and communication ...styles, without addressing systematic implementation. This article describes how an interdisciplinary team, led by advanced practice nurses, developed and implemented a collaborative practice model to deliver bad news on a unit that had struggled with inconsistencies. Using evidence-based practices, the authors explored current processes, role perceptions and expectations, and perceived barriers to developing the model, which is now the standard of care and an example of interprofessional team collaboration across the healthcare system. This model for delivering bad news can be easily adapted to meet the needs of other clinical units. .
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The incretin hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP), are thought to be the main drivers of insulin secretion in individuals with sulfonylurea ...(SU)‐treated KCNJ11 permanent neonatal diabetes. The aim of this study was to assess for the first time the incretin hormone response to carbohydrate and protein/fat in adults with sulfonylurea‐treated KCNJ11 permanent neonatal diabetes compared with that of controls without diabetes. Participants were given a breakfast high in carbohydrate and an isocaloric breakfast high in protein/fat on two different mornings. Incremental area under the curve and total area under the curve (0‐240 minutes) for total GLP‐1 and GIP were compared between groups, using non‐parametric statistical methods. Post‐meal GLP‐1 and GIP secretion were similar in cases and controls, suggesting this process is adenosine triphosphate‐sensitive potassium channel‐independent. Future research will investigate whether treatments targeting the incretin pathway are effective in individuals with KCNJ11 permanent neonatal diabetes who do not have good glycemic control on sulfonylurea alone.
Insulin secretion in individuals with sulfonylurea‐treated KCNJ11 permanent neonatal diabetes is thought to be dependent on non‐ adenosine triphosphate‐sensitive potassium channel pathways; for example, incretin hormones. We assessed incretin hormone secretion after different foods in individuals with sulfonylurea‐treated KCNJ11 permanent neonatal diabetes, in comparison with people without diabetes. Patterns of glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 secretion after protein/fat and carbohydrate meals were similar in cases and controls. An intact incretin pathway might provide a therapeutic target for individuals with sulfonylurea‐treated KCNJ11 permanent neonatal diabetes who require adjunctive therapy to optimize glycemic control.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tacrolimus is a substrate for P‐glycoprotein (P‐gp) and cytochrome (CYP) P4503A. P‐gp is encoded by the multiple drug resistance gene MDR1 and CYP3A is the major enzyme responsible for tacrolimus ...metabolism. Both MDR1 and CYP3A5 genes have multiple single nucleotide polymorphisms. The objective of this study was to evaluate whether the MDR1 exon21 and exon26 polymorphisms and the CYP3A5 polymorphism are associated with tacrolimus disposition in pediatric heart transplant patients. At 3, 6 and 12 months post transplantation, a significant difference in tacrolimus blood level per dose/kg/day was found between the CYP3A5 *1/*3 (CYP3A5 expressor) vs. *3/*3 (nonexpressor) genotypes with the *1/*3 patients requiring a larger tacrolimus dose to maintain the same blood concentration. There were no significant differences in tacrolimus blood level per dose/kg/day between MDR1 exon21 G2677T and exon 26 C3435T at 3 months, but both were found to have a significant association with tacrolimus blood level per dose/kg/day at 6 and 12 months. We conclude that specific genotypes of MDR1 and CYP3A5 in pediatric heart transplant patients require larger tacrolimus doses to maintain their tacrolimus blood concentration, and that this information could be used prospectively to manage patient's immunosuppressive therapy.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The concept of a carbimazole embryopathy underlies current Endocrine Society advice to avoid this drug in early pregnancy, favouring propylthiouracil as an alternative for the treatment of maternal ...hyperthyroidism. We aimed to establish whether suspected spontaneous reporting of adverse drug reactions in the UK via the Yellow Card Scheme supports a carbimazole embryopathy and the lack of association between propylthiouracil and congenital anomalies. All birth defects related to maternal treatment with carbimazole or propylthiouracil reported over a 47-year period via the Yellow Card Scheme were analysed. 57 cases with 97 anomalies were reported following in utero exposure to carbimazole. These anomalies included aplasia cutis, choanal atresia, tracheo-oesophageal fistula, and patent vitellointestinal duct, which have previously been reported in association with carbimazole/methimazole exposure in utero. Only 6 cases with 11 anomalies were reported for propylthiouracil, all within the last 15 years. Therefore, these findings may support a carbimazole embryopathy. There are few birth defects associated with propylthiouracil, but this should be interpreted in the context of higher historical prescription rates for carbimazole.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Urinary C-peptide creatinine ratio (UCPCR) is a non-invasive and convenient way of assessing endogenous insulin production. Adjusting for urine creatinine levels allows for differences in urine ...concentration. Creatinine excretion is known to be higher in men due to gender differences in muscle mass. We investigated the impact of gender on UCPCR.
One hundred and seventy-six subjects underwent a mixed meal tolerance test (MMTT). We looked at the relationship between UCPCR on urine C-peptide and creatinine excretion rates using timed post-meal urine samples. A further 415 subjects had two-hour post-meal UCPCR measurements in order to derive gender-specific percentiles for different diabetes subgroups and controls.
UCPCR was 1.48-fold higher in women (n=78) than men (n=98), median (interquartile range IQR): 1.88 (0.49-3.49) men versus 2.88 (1.58-4.91) nmol mmol(-1) women, P=0.01. This reflects a gender difference in creatinine excretion rates (11.5 8.3-13.7 men versus 8.2 5.6-9.1 women μmol min(-1) P<0.001). C-peptide excretion rate was similar in men and women (19.8 5.2-37.0 versus 22.1 7.4-40.5 pmol min(-1), P=0.7). UCPCR was higher in women in all subgroups defined by diabetes classification and treatment, except long-term type 1 diabetes in whom C-peptide secretion was minimal.
Gender affects UCPCR, with higher values found in women. This results from lower urine creatinine reflecting gender differences in muscle mass. This necessitates gender-specific ranges for accurate interpretation of UCPCR results.
Various polymorphisms of the
MDR1 gene that encodes for P-glycoprotein (P-gp), a transmembrane pump, have been identified. A silent mutation C3435T in exon 26 and a G2677T mutation in exon 21 have ...been correlated with P-gp expression and function in humans. The objectives of this study were (a) to determine whether the
MDR1 exon 21 and exon 26 polymorphisms were related to steroid weaning in a pediatric heart transplant (HTx) population, and (b) to determine whether an association exist between the
MDR1 exon 21 and exon 26 polymorphisms in these patients. Sixty-nine pediatric HTx patients were studied.
MDR1 genotyping was determined by polymerase chain reaction amplification, sequencing the DNA, and sequence evaluation using Polyphred software (University of Washington) to identify genotypes. The steroid dose at 1 year post-transplantation was recorded. For steroid weaning at one year post-HTx for
MDR1 C3435T, 12 of 18 (67%) patients in the CC genotype were still on prednisone, whereas only 18 of 47 (38%) of the CT/TT group were still receiving prednisone (
p = 0.04). Similar results were observed for the
MDR1 G2677T genotyping and steroid weaning. Forty-three of 46 patients (93.5%) who have
MDR1 C3435T allele also have a mutant G2677T allele (
p < 0.001). We conclude that (a) a significantly larger number of
MDR1 3435 CC HTx patients remain on steroids at 1 year after transplantation, and (b) the
MDR1 C3435T genotype is associated with the G2677 genotype in pediatric HTx patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract First‐line genetic investigations for rare neurological and developmental conditions have limitations in their ability to detect and characterize copy number variants (CNVs). Whole genome ...sequencing (WGS) offers potential advantages over other methods of CNV analysis. We aimed to demonstrate the utility of CNV detection using WGS through description of three clinical cases. WGS analysis was undertaken in three patients presenting to a national rare disease service, in whom a genetic aetiology remained uncertain after gene panel testing or microarray based comparative genomic hybridization (array CGH). In all three cases, WGS identified CNVs and confirmed zygosity and pathogenicity, resulting in genetic diagnoses of PRKN ‐related Parkinson disease, TAOK1 ‐related neurodevelopmental disorder, and AP1G1 ‐related Usmani‐Riazuddin syndrome. This case series demonstrates the value of WGS analysis in identifying or better characterizing CNVs that were missed or deemed of uncertain significance using conventional methods of testing. Importantly, our approach facilitated accurate genetic diagnosis and counselling for the families involved.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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