Frequency of C3435T polymorphism of MDR1 gene in African people

The variability of P-glycoprotein expression between individuals is linked to a C3435T polymorphism of the human MDR1 gene. Concentration of P-glycoprotein in intestinal epithelial cells and in a subset of lymphoid cells is substantially lower in people with the T/T genotype than those with the C/C genotype. We compared allele frequencies of the C3435T polymorphism in random samples of west African, African American, white, and Japanese people. We recorded a significantly higher frequency of the C/C genotype in West Africans and African Americans (142 of 172 [83%] and 25 of 41 [61%], respectively), than in white people (139 of 537 [26%]) (p<0.0001). These findings could affect use of drugs that are P-glycoprotein substrates (such as HIV-1 protease inhibitors and ciclosporin) in African populations.     

Health care utilization,prognosis and outcomes of vestibular disease in primary care settings: systematic review

Vertigo and dizziness are frequent complaints in primary care that lead to extensive health care utilization. The objective of this systematic review was to examine health care of patients with vertigo and dizziness in primary care settings. Specifically, we wanted to characterize health care utilization, therapeutic and referral behaviour and to examine the outcomes associated with this. A search of the MEDLINE and EMBASE databases was carried out in May 2015 using the search terms ‘vertigo’ or ‘dizziness’ or ‘vestibular and primary care’ to identify suitable studies. We included all studies that were published in the last 10 years in English with the primary diagnoses of vertigo, dizziness and/or vestibular disease. We excluded drug evaluation studies and reports of adverse drug reactions. Data were extracted and appraised by two independent reviewers; 16 studies with a total of 2828 patients were included. Mean age of patients ranged from 45 to 79 with five studies in older adults aged 65 or older. There were considerable variations in diagnostic criteria, referral and therapy while the included studies failed to show significant improvement of patient-reported outcomes. Studies are needed to investigate current practice of care across countries and health systems in a systematic way and to test primary care-based education and training interventions that improve outcomes.     

Strategic information management plans: the basis for systematic information management in hospitals.

Information management in hospitals is a complex task. In order to reduce complexity, we distinguish strategic, tactical, and operational information management. This is essential, because each of these information management levels views hospital information systems from different perspectives, and therefore uses other methods and tools. Since all these management activities deal only in part with computers, but mainly with human beings and their social behavior, we define a hospital information system as a sociotechnical subsystem of a hospital. Without proper strategic planning it would be a matter of chance, if a hospital information system would fulfil the information strategies goals. In order to support strategic planning and to reduce efforts for creating strategic plans, we propose a practicable structure.     

Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder associated with increased risk of intrauterine fetal death and prematurity. There is increasing evidence that genetically determined dysfunction in the canalicular ABC transporters bile salt export pump (BSEP, ABCB11) and multidrug resistance protein 3 (MDR3, ABCB4) might be risk factors for ICP development. This study aimed to (i). describe the extent of genetic variability in BSEP and MDR3 in ICP and (ii). identify new disease-causing mutations. Twenty-one women with ICP and 40 women with uneventful pregnancies were recruited between April 2001 and April 2003. Sequencing of BSEP and MDR3 spanned 8-10 kb per gene and comprised the promoter region and 100-350 bp of the flanking intronic region around each exon. DNA sequencing of polymerase chain reaction fragments was performed on an ABI3700 capillary sequencer. MDR3 promoter activity of promoter constructs carrying different ICP-specific mutations was studied using reporter assays. A total of 37 and 51 variant sites were detected in BSEP and MDR3, respectively. Three non-synonymous sites in codons for evolutionarily conserved amino acids were specific for the ICP collective (BSEP, N591S; MDR3, S320F and G762E). Furthermore, four ICP-specific splicing mutations were detected in MDR3 [intron 21, G(+1)A; intron 25, G(+5)C and C(-3)G; and intron 26, T(+2)A]. Activity of the mutated MDR3 promoter was similar to that observed for the wild-type promoter. Our data further support an involvement of MDR3 genetic variation in the pathogenesis of ICP, whereas analysis of BSEP sequence variation indicates that this gene is probably less important for the development of pregnancy-associated cholestasis.