A collaborative, double-blind randomized study of cetiedil citrate in sickle cell crisis

We have recently completed a double-blind, placebo-controlled, noncrossover study, the goal of which was to determine whether cetiedil citrate (cetiedil) could affect the course of vaso-occlusive crises in sickle cell disease. Patients, who presented to the emergency room at least 4 but no more than 24 hours after the onset of a painful vasoocclusive crisis severe enough to require hospitalization, were considered candidates for the study. Each patient received either placebo or cetiedil at one of the following three dosages: 0.2, 0.3, or 0.4 mg/kg body weight. The assigned drug dosage was given as a 30 minute intravenous infusion every 8 hours for 4 consecutive days. A total of 67 patients was enrolled in the study. Cetiedil, at its highest dosage (0.4 mg/kg body weight), was found to be significantly superior to placebo both in reducing the number of painful sites present on all 4 treatment days and in shortening the total time in crisis. No serious adverse reactions were observed during the course of the study. We conclude that cetiedil, given at a dosage of 0.4 mg/kg body weight, is therapeutically advantageous for sickle cell crisis.     

A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43)

We report a novel mutation in the amyloid precursor protein gene (APP I716V) which probably leads to familial early onset Alzheimer's disease with an onset age in the mid 50s. Cells transfected with cDNAs bearing this mutation produce more A beta 1-42(43) than those transfected with wild-type APP and this effect is additive with that of the previously reported APP V717I mutation thus providing a novel approach for further increasing A beta 1-42(43) in model systems.      

Reasons and Barriers for Using a Patient Portal: Survey Among Patients With Diabetes Mellitus

Background

The use of a Web portal for patients with diabetes mellitus to access their own personal health record may result in improved diabetes outcomes. However, the adoption by patients is slow. This may be caused by patient characteristics, but also by the content, layout, and promotion of the portal. Detailed knowledge about this could help increase patients’ participation in Web portals.

Objective

The aim was to study the opinions of patients with diabetes and identify perceived barriers to using a Web portal to optimize its use.

Methods

We conducted a survey among patients with type 1 and type 2 diabetes mellitus from 62 primary care practices and 1 outpatient hospital clinic in the central area of the Netherlands who all used the same electronic health record with a Web portal. Questionnaires about patient characteristics, opinions about reasons for use or nonuse, and about portal content were sent to 1500 patients with a login and 3000 patients without a login to the Web portal. Patient groups were stratified according to login frequency. Demographic and diabetes-related variables were analyzed with multivariable regression analysis.

Results

The total response rate was 66.63% (2391/4399); 1390 of 4399 patients (31.60%) were eligible for analysis. There were 413 regular users (login frequency more than once) and 758 nonusers (no login). Most nonusers (72.4%) stated that the main reason for not requesting a login was that they were unaware of the existence of the portal. Other barriers reported by patients were disinterest in managing their own disease (28.5%, 216/758) and feelings of inadequacy with the use of computers and Internet (11.6%, 88/758). Patients treated by a general practitioner were more frequently nonusers compared to patients treated by an internist (78.8%, 666/846 vs 28.3%, 92/325; P<.001) and more users than nonusers became aware of the Web portal through their physician (94.9%, 392/413 vs 48.8%, 102/209; P<.001). Nonusers perceived specific portal content as not as useful as regular users did, especially access to laboratory values (71.7%, 383/534 vs 92.3%, 372/403), rereading clinic visits (61.3%, 320/522 vs 89.6%, 360/402), e-messaging (52.0%, 262/504 vs 74.6%, 299/401), and uploading results to the glucose diary (45.3%, 229/506 vs 74.0%, 288/400; all P<.001).

Conclusions

Our study shows that unawareness of the patient portal is the main barrier of enrollment. Users and nonusers perceive the usefulness of the portal differently and do not have the same recommendations for additional functionalities. To increase patients’ participation in a Web portal, the unawareness of its existence and its possibilities need to be addressed by their health care professionals.     

I am pregnant and my husband has diabetes. Is there a risk for my child? A qualitative study of questions asked by email about the role of genetic susceptibility to diabetes

Background  

Diabetes Mellitus is a global health problem. Scientific knowledge on the genetics of diabetes is expanding and is more and more utilised in clinical practice and primary prevention strategies. Health consumers have become increasingly interested in genetic information. In the Netherlands, the National Genetic Research and Information Center provides online information about the genetics of diabetes and thereby offers website visitors the opportunity to ask a question per email. The current study aims at exploring people's need of (additional) information about the role of inheritance in diabetes. Results may help to tailor existing clinical and public (online) genetic information to the needs of an increasing population at risk for diabetes.     

A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2

Type I and type II keratins form the heteropolymeric intermediate filament cytoskeleton, which is the main stress-bearing structure within epithelial cells. Pachyonychia congenita (PC) is a group of autosomal dominant disorders whose most prominent phenotype is hypertrophic nail dystrophy accompanied by other features of ectodermal dysplasia. It has been shown previously that mutations in either K16 or K6a, which form a keratin expression pair, produce the PC-1 variant (MIM 184510). Mutations in K17 alone, an unpaired accessory keratin, result in the PC-2 phenotype (MIM 184500). Here, we describe a family with PC-2 in which the K17 locus on 17q was excluded and linkage to the type II keratin locus on 12q was obtained (Z max 3.31 at straight theta = 0). Mutation analysis of candidate keratins revealed the first reported missense mutation in K6b, implying that this keratin is the previously unknown expression partner of K17, analogous to the K6a/K16 pair. Co-expression of these genes was confirmed by in situ hybridization and immunohistochemical staining. These results reveal the hitherto unknown role of the K6b isoform in epithelial biology, as well as genetic heterogeneity in PC-2.