Screening for Rare Coding Variants That Associate With the QTc Interval in Iceland.

Background Long-QT syndrome (LQTS) is a cardiac repolarization abnormality that can lead to sudden cardiac death. The most common causes are rare coding variants in the genes KCNQ1, KCNH2, and SCN5A. The data on LQTS epidemiology are limited, and information on expressivity and penetrance of pathogenic variants is sparse. Methods and Results We screened for rare coding variants associated with the corrected QT (QTc) interval in Iceland. We explored the frequency of the identified variants, their penetrance, and their association with severe events. Twelve variants were associated with the QTc interval. Five in KCNQ1, 3 in KCNH2, 2 in cardiomyopathy genes MYBPC3 and PKP2, and 2 in genes where coding variants have not been associated with the QTc interval, ISOC1 and MYOM2. The combined carrier frequency of the 8 variants in the previously known LQTS genes was 530 per 100 000 individuals (1:190). p.Tyr315Cys and p.Leu273Phe in KCNQ1 were associated with having a mean QTc interval longer than 500 ms (P=4.2×10-7; odds ratio [OR], 38.6; P=8.4×10-10, OR, 26.5; respectively), and p.Leu273Phe was associated with sudden cardiac death (P=0.0034; OR, 2.99). p.Val215Met in KCNQ1 was carried by 1 in 280 Icelanders, had a smaller effect on the QTc interval (P=1.8×10-44; effect, 22.8 ms), and did not associate with severe clinical events. Conclusions The carrier frequency of associating variants in LQTS genes was higher than previous estimates of the prevalence of LQTS. The variants have variable effects on the QTc interval, and carriers of p.Tyr315Cys and p.Leu273Phe have a more severe disease than carriers of p.Val215Met. These data could lead to improved identification, risk stratification, and a more precise clinical approach to those with QTc prolongation.

Islet transplantation as safe and efficacious method to restore glycemic control and to avoid severe hypoglycemia after donor organ failure in pancreas transplantation.

The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas retransplantation. Ten patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months. The primary end point of HbA1c <7.0% and freedom of severe hypoglycemia was met by nine of 10 patients after follow-up after islet transplantation and in all three patients in the pancreas retransplantation group, but by none of the patients in the group without retransplantation (n = 7). Insulin requirement was reduced by 50% after islet transplantation. Kidney function (eGFR) declined with a rate of -1.0 mL ± 1.2 mL/min/1.73 m2 per year during follow-up after islet transplantation, which tended to be slower than in the group without retransplantation (P = .07). Islet transplantation after deceased donor pancreas transplant failure is a method that can safely improve glycemic control and reduce the incidence of severe hypoglycemia and thus establish similar glycemic control as after initial pancreas transplantation, despite the need of additional exogenous insulin.

[Old people in the Emergency Department; Icelandic results from the InterRAI multinational ED study]. / Eldra fólk á brádadeild: íslenskar nidurstödur úr fjölþjódarannsókn InterRAI.

INTRODUCTION: Old people attend emergency departments (ED´s) in increasing numbers. Old people have age related changes in all organ systems and tend to have multiple chronic diseases, be on multiple medications and often have physical and cognitive functional impairments. Hence, they have complex health and social service needs. The purpose of this study was to describe function and geriatric syndromes of old people who present at Landspitali Emergency Department, Iceland, with comparison to ED´s in six other countries. MATERIAL AND METHODS: A prospective descriptive study of people (>75 year´s) attending ED´s in seven countries, including Iceland. The InterRAI assessment tool for ED´s was used by nurses to assess participants. RESULTS: At Landspitali ED, 202 individuals were assessed, of whom 55% were women. Of the 202 individuals, 34% attended the ED within 90 days and of those 48% lived alone. On admission to the ED, 59% had physical or cognitive functional impairment; 13% had only cognitive impairment and 36% were unable to walk without assistance. Caregiver distress was identified in 28% and 11% felt overwhelming burden. From the ED, 46% were admitted to the hospital. Compared with foreign results greater number of Icelandic participants lived alone and caregiver's distress was slightly higher (28% vs. 18%). Fewer individuals in Iceland were admitted to a hospital and Iceland had higher admission rate to rehabilitation compared with the overall group. CONCLUSION: Geriatric syndromes and functional impairment afflicted majority of old people who attended the Landspitali ED. These observations should be taken into account in ED design and care planning for old people to maximize efficiency, safety and quality.