Structured education can improve primary-care management of headache: the first empirical evidence, from a controlled interventional study

Headache disorders are under-recognized and under-diagnosed. A principal factor in their suboptimal management is lack of headache-related training among health-care providers, especially in primary care. In Estonia, general practitioners (GPs) refer many headache patients to neurological specialist services, mostly unnecessarily. GPs request diagnostic investigations, which are usually unhelpful and therefore wasteful. GP-made headache diagnoses are often arcane and non-specific, and treatments based on these are inappropriate. The aim of this study was to develop, implement and test an educational model intended to improve headache-related primary health care in Estonia.This was a controlled study consisting of baseline observation, intervention and follow-up observation using the same measures of effect. It involved six GPs in Põlva and the surrounding region in Southern Estonia, together with their future patients presenting consecutively with headache as their main complaint, all with their consent. The primary outcome measure was referral rate (RR) to neurological specialist services. Secondary measures included number of GP-requested investigations, GP-made headache diagnoses and how these conformed to standard terminology (ICD-10), and GP-recommended or initiated treatments.RR at baseline (n = 490) was 39.5 %, falling to 34.7 % in the post-intervention group (n = 295) (overall reduction 4.8 %; p = 0.21). In the large subgroup of patients (88 %) for whom GPs made clearly headache-related ICD-10 diagnoses, RR fell by one fifth (from 40 to 32 %; p = 0.08), but the only diagnosis-related RR that showed a statistically significant reduction was (pericranial) myalgia (19 to 3 %; p = 0.03). There was a significant increase towards use of more specific diagnoses. Use of investigations in diagnosing headache reduced from 26 to 4 % (p < 0.0001). Initiation of treatment by GPs increased from 58 to 81 % (p < 0.0001).These were modest changes in GPs entrenched behaviour. Nevertheless they were empirical evidence that GPs practice in the field of headache could be improved by structured education. Furthermore, the changes were likely to be cost-saving. To our knowledge this study is the first to produce such evidence

Multisite phosphorylation networks as signal processors for Cdk1

The order and timing of cell cycle events is controlled by changing substrate specificity and different activity thresholds of cyclin-dependent kinases (CDK). However, it is not understood how a single protein kinase can trigger hundreds of switches in a sufficiently time-resolved fashion. We show that the cyclin-Cdk1-Cks1-dependent phosphorylation of multisite targets in Saccharomyces cerevisiae is controlled by key substrate parameters including distances between phosphorylation sites, the distribution of serines and threonines as phospho-acceptors, and the positioning of cyclin-docking motifs. The component mediating the key interactions in this process is Cks1, the phospho-adaptor subunit of the cyclin-Cdk1-Cks1 complex. We propose that variation of these parameters within the networks of phosphorylation sites in different targets provides a wide range of possibilities for the differential amplification of Cdk1 signals, providing a mechanism to generate a wide range of thresholds in the cell cycle