A cluster randomised controlled trial of a pharmacist-led collaborative intervention to improve statin prescribing and attainment of cholesterol targets in primary care

Background: Small trials with short term follow up suggest pharmacists’ interventions targeted at healthcare professionals can improve prescribing. In comparison with clinical guidance, contemporary statin prescribing is sub-optimal and achievement of cholesterol targets falls short of accepted standards, for patients with atherosclerotic vascular disease who are at highest absolute risk and who stand to obtain greatest benefit. We hypothesised that a pharmacist-led complex intervention delivered to doctors and nurses in primary care, would improve statin prescribing and achievement of cholesterol targets for incident and prevalent patients with vascular disease, beyond one year.<p></p> Methods: We allocated general practices to a 12-month Statin Outreach Support (SOS) intervention or usual care. SOS was delivered by one of 11 pharmacists who had received additional training. SOS comprised academic detailing and practical support to identify patients with vascular disease who were not prescribed a statin at optimal dose or did not have cholesterol at target, followed by individualised recommendations for changes to management. The primary outcome was the proportion of patients achieving cholesterol targets. Secondary outcomes were: the proportion of patients prescribed simvastatin 40 mg with target cholesterol achieved; cholesterol levels; prescribing of simvastatin 40 mg; prescribing of any statin and the proportion of patients with cholesterol tested. Outcomes were assessed after an average of 1.7 years (range 1.4–2.2 years), and practice level simvastatin 40 mg prescribing was assessed after 10 years.<p></p> Findings: We randomised 31 practices (72 General Practitioners (GPs), 40 nurses). Prior to randomisation a subset of eligible patients were identified to characterise practices; 40% had cholesterol levels below the target threshold. Improvements in data collection procedures allowed identification of all eligible patients (n = 7586) at follow up. Patients in practices allocated to SOS were significantly more likely to have cholesterol at target (69.5% vs 63.5%; OR 1.11, CI 1.00–1.23; p = 0.043) as a result of improved simvastatin prescribing. Subgroup analysis showed the primary outcome was achieved by prevalent but not incident patients. Statistically significant improvements occurred in all secondary outcomes for prevalent patients and all but one secondary outcome (the proportion of patients with cholesterol tested) for incident patients. SOS practices prescribed more simvastatin 40 mg than usual care practices, up to 10 years later.<p></p> Interpretation: Through a combination of educational and organisational support, a general practice based pharmacist led collaborative intervention can improve statin prescribing and achievement of cholesterol targets in a high-risk primary care based population

Amyloid-β accumulation in the CNS in human growth hormone recipients in the UK

Human-to-human transmission of Creutzfeldt–Jakob disease (CJD) has occurred through medical procedures resulting in iatrogenic CJD (iCJD). One of the commonest causes of iCJD was the use of human pituitary-derived growth hormone (hGH) to treat primary or secondary growth hormone deficiency. As part of a comprehensive tissue-based analysis of the largest cohort yet collected (35 cases) of UK hGH-iCJD cases, we describe the clinicopathological phenotype of hGH-iCJD in the UK. In the 33/35 hGH-iCJD cases with sufficient paraffin-embedded tissue for full pathological examination, we report the accumulation of the amyloid beta (Aβ) protein associated with Alzheimer’s disease (AD) in the brains and cerebral blood vessels in 18/33 hGH-iCJD patients and for the first time in 5/12 hGH recipients who died from causes other than CJD. Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD and variant CJD. These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and had a seeding effect in the brains of around 50% of all hGH recipients, producing an AD-like neuropathology and cerebral amyloid angiopathy (CAA), regardless of whether CJD neuropathology had occurred. These findings indicate that Aβ seeding can occur independently and in the absence of the abnormal prion protein in the human brain. Our findings provide further evidence for the prion-like seeding properties of Aβ and give insights into the possibility of iatrogenic transmission of AD and CAA

Primary and secondary outcomes.

<p>For binary outcomes, summaries are presented as number (percent) and treatment effects as odds ratios (SOS vs Usual Care) with corresponding 95% confidence intervals estimated from logistic regression models, adjusted for matched pairs. For continuous outcomes (*), summaries are presented as geometric means and treatment effects are presented as ratios (SOS vs Usual Care) with corresponding 95% confidence intervals estimated from linear regression models of the logged values, adjusted for matched pairs.</p><p>Primary and secondary outcomes.</p

Primary and secondary outcomes in incident and prevalent patients.

<p>For binary outcomes, summaries are presented as number (percent) and treatment effects as odds ratios (SOS vs Usual Care) with corresponding 95% confidence intervals estimated from logistic regression models, adjusted for matched pairs. For continuous outcomes (*), summaries are presented as geometric means and treatment effects are presented as ratios (SOS vs Usual Care) with corresponding 95% confidence intervals estimated from linear regression models of the logged values, adjusted for matched pairs.</p><p>Primary and secondary outcomes in incident and prevalent patients.</p

Baseline patient characteristics.

<p>Baseline patient characteristics.</p

Long term Simvastatin 40 mg prescribing in Intervention vs. Usual Care practices.

<p>Long term Simvastatin 40 mg prescribing in Intervention vs. Usual Care practices.</p

Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study

Objective To perform prion protein gene (PRNP) codon 129 analysis in DNA extracted from appendix tissue samples that had tested positive for disease associated prion protein. Design Reanalysis of positive cases identified in a retrospective anonymised unlinked prevalence study of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom. Study samples Three positive appendix tissue samples out of 12 674 samples of appendix and tonsil tested for disease associated prion protein. The patients from whom these samples were obtained were aged 20-29 years at the time of surgery, which took place in 1996-9. Setting Pathology departments in two tertiary centres in England and Scotland. Results Adequate DNA was available for analysis in two of the three specimens, both of which were homozygous for valine at codon 129 in the PRNP. Conclusions This is the first indication that the valine homozygous subgroup at codon 129 in the PRNP is susceptible to vCJD infection. All tested clinical cases of vCJD have so far occurred in the methionine homozygous subgroup, and a single case of probable iatrogenic vCJD infection has been identified in one patient who was a methionine/valine heterozygote at this genetic locus. People infected with vCJD with a valine homozygous codon 129 PRNP genotype may have a prolonged incubation period, during which horizontal spread of the infection could occur either from blood donations or from contaminated surgical instruments used on these individuals during the asymptomatic phase of the illness

Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: U.K. cases 1991-2002

Human prion diseases can occur as an idiopathic disorder (sporadic Creutzfeldt–Jakob disease) or can be acquired, as is the case for variant Creutzfeldt–Jakob disease. These disorders are characterized by the accumulation of a protease-resistant form of the host-encoded prion protein termed PrPSc in the brains of affected individuals. PrPSc has been proposed to be the principal, if not sole, component of the infectious agent, with its accumulation in the central nervous system the primary event leading to neurodegeneration. A major question remains as to whether self-propagating structural differences in PrPSc might account for the clinicopathological diversity evident in Creutzfeldt–Jakob disease and whether different prion protein types underlie the existence of different strains of causative agent. Here, we describe the results of a large-scale biochemical study of PrPSc from autopsy-proved cases of variant Creutzfeldt–Jakob disease (n = 59) and compare these with cases of sporadic Creutzfeldt–Jakob disease (n = 170) in the United Kingdom over the period 1991 to 2002. The results show PrPSc in variant Creutzfeldt–Jakob disease to be remarkably stereotyped. In contrast, considerable heterogeneity in PrPSc exists both between and within cases of sporadic Creutzfeldt–Jakob disease