Dominant control region of the human β- like globin gene cluster

The structure and regulation of the human β -like globin gene cluster has been studied extensively. Genetic disorders connected with this gene cluster are responsible for human diseases associated with high levels of morbidity and mortality, such as β-thalassaemia and sickle cell anaemia. The work described in this thesis is concerned with a novel tissue-specific regulatory element. ... Zie: Summar

How usual is usual care in pragmatic intervention studies in primary care? An overview of recent trials

Background Because pragmatic trials are performed to determine if an intervention can improve current practice, they often have a control group receiving 'usual care'. The behaviour of caregivers and patients in this control group should be influenced by the actions of researchers as little as possible. Guidelines for describing the composition and management of a usual care control group are lacking. Aim To explore the variety of approaches to the usual care concept in pragmatic trials; and evaluate the influence of the study design on the behaviour of caregivers and patients in a usual care control group. Design of study Review of 73 pragmatic trials in primary care with a usual care control group published between January 2005 and December 2009 in the British Medical Journal, the British Journal of General Practice, and Family Practice. Outcome measures were: description of the factors influencing caregiver and patients in a usual care control group related to an individual randomised design versus cluster randomisation. Results In total, 38 individually randomised trials and 35 cluster randomised trials were included. In most trials, caregivers had the freedom to treat control patients according to their own insight; in two studies, treatment options were restricted. Although possible influences on the behaviour of control caregivers and control patients were more often identified in individually randomised trials, these influences were also present in cluster randomised trials. The description of instructions and information provided to the control group was often insufficient, which made evaluation of the trials difficult. Conclusion Researchers in primary care medicine should carefully consider the design of a usual care control group, especially with regard to minimising the risk of study-induced behavioural change. It is recommended that an adequate description of the information is provided to control caregivers and control patients. A proposal is made for an extension to the CONSORT statement that requires authors to specify details of the usual care control group.Public Health and primary car

Exploring the variation in implementation of a COPD disease management programma and its impact on health outcomes

This study aims to (1) examine the variation in implementation of a 2-year chronic obstructive pulmonary disease (COPD) management programme called RECODE, (2) analyse the facilitators and barriers to implementation and (3) investigate the influence of this variation on health outcomes. Implementation variation among the 20 primary-care teams was measured directly using a self-developed scale and indirectly through the level of care integration as measured with the Patient Assessment of Chronic Illness Care (PACIC) and the Assessment of Chronic Illness Care (ACIC). Interviews were held to obtain detailed information regarding the facilitators and barriers to implementation. Multilevel models were used to investigate the association between variation in implementation and change in outcomes. The teams implemented, on average, eight of the 19 interventions, and the specific package of interventions varied widely. Important barriers and facilitators of implementation were (in)sufficient motivation of healthcare provider and patient, the h

Effectiveness of integrated disease management for primary care chronic obstructive pulmonary disease patients: results of cluster randomised trial.

__Objective__ To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with usual care. __Design__ 24 month, multicentre, pragmatic cluster randomised controlled trial __Setting__ 40 general practices in the western part of the Netherlands __Participants__ Patients with COPD according to GOLD (Global Initiative for COPD) criteria. Exclusion criteria were terminal illness, cognitive impairment, alcohol or drug misuse, and inability to fill in Dutch questionnaires. Practices were included if they were willing to create a multidisciplinary COPD team. __Intervention__ General practitioners, practice nurses, and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice, including early recognition of exacerbations and self management, smoking cessation, physiotherapeutic reactivation, optimal diagnosis, and drug adherence. Additionally, the course served as a network platform and collaborating healthcare providers designed an individual practice plan to integrate integrated disease management into daily practice. The control group continued usual care (based on

Public transport policy in the Netherlands

Dutch public transport as a part of transport policy.Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Expression of carbonic anhydrase II (CA II) promoter-reporter fusion genes in multiple tissues of transgenic mice does not replicate normal patterns of expression indicating complexity of CA II regulation in vivo

Although the proximal, 5′ 115 bp of the human carbonic anhydrase II (CA II) gene was sufficient for expression of a reporter gene in some transfected cell lines, we found previously that 1100 bp of this promoter (or 500 bp of the mouse CA II promoter) was not sufficient for expression in transgenic mice. We have now studied the expression of linked reporter genes in mice transgenic for either (1) 11 kb of the human 5′ promoter or (2) 8 kb of the human 5′ promoter with mouse sequences from the first exon, part of the first intron (since a CpG island spans this region), and the 3′ sequences of the gene. Expression was found in both cases, but the tissue specificity was not appropriate for CA II. Although there was a difference in the sensitivity of the assays used, the first construct led to expression in many tissues, while the second construct was expressed only in spleen. These findings indicate considerable complexity of DNA control regions for in vivo CA II expression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44160/1/10528_2004_Article_BF00554600.pd

Triptan use after starting prophylactic migraine treatment: a retrospective cohort study in a primary care population.

Background: Clinical trials on the prophylactic effect of propranolol and metoprolol for migraine show that starting this medication leads to a decrease in the use of attack medication of 0.9–8.9 doses per month. However, studies in daily practice are lacking. Methods: We compared the number of triptans prescribed in the six months before and the six months after the start of propranolol/metoprolol in a Dutch national representative primary care cohort. Results: Of the 168 triptan-using patients who started with propranolol or metoprolol, the number of triptans prescribed before starting was 4.6 doses per month. The number of triptans prescribed six months before compared with six months after starting propranolol/metoprolol decreased with 1.0 dose per month (Wilcoxon rank test; p=0.000). Conclusion: In this primary care population, although the number of triptans prescribed decreased after starting propranolol or metoprolol, the decrease is relatively small compared to data from clinical trials. (aut.ref.