Hepatitis C - Assessment to Treatment Trial (HepCATT) in primary care: study protocol for a cluster randomised controlled trial.

BACKGROUND: Public Health England (PHE) estimates that there are upwards of 160,000 individuals in England and Wales with chronic hepatitis C virus (HCV) infection, but until now only around 100,000 laboratory diagnoses have been reported to PHE and of these 28,000 have been treated. Targeted case-finding in primary care is estimated to be cost-effective; however, there has been no robust randomised controlled trial evidence available of specific interventions. Therefore, this study aims to develop and conduct a complex intervention within primary care and to evaluate this approach using a cluster randomised controlled trial. METHODS/DESIGN: A total of 46 general practices in South West England will be randomised in a 1:1 ratio to receive either a complex intervention comprising: educational training on HCV for the practice; poster and leaflet display in the practice waiting rooms to raise awareness and encourage opportunistic testing; a HCV risk prediction algorithm based on information on possible risk markers in the electronic patient record run using Audit + software (BMJ Informatica). The audit will then be used to recall and offer patients a HCV test. Control practices will follow usual care. The effectiveness of the intervention will be measured by comparing number and rates of HCV testing, the number and proportion of patients testing positive, onward referral, rates of specialist assessment and treatment in control and intervention practices. Intervention costs and health service utilisation will be recorded to estimate the NHS cost per new HCV diagnosis and new HCV patient initiating treatment. Longer-term cost-effectiveness of the intervention in improving quality-adjusted life years (QALYs) will be extrapolated using a pre-existing dynamic health economic model. Patients' and health care workers' experiences and acceptability of the intervention will be explored through semi-structured qualitative interviews. DISCUSSION: This trial has the potential to make an important impact on patient care and will provide high-quality evidence to help general practitioners make important decisions on HCV testing and onward referral. If found to be effective and cost-effective the intervention is readily scalable and can be used to support the implementation of NICE recommendations on HCV case-finding. TRIAL REGISTRATION: ISRCTN61788850 . Registered on 24 April 2015; Protocol Version: 2.0, 22 May 2015.

Genotyping cytochrome P450 3A5 using the Light Cycler.

Cytochrome P450 3A5 (CYP3A5) is involved in the biotransformation of many orally administered drugs, some of which are dose optimized using therapeutic drug monitoring. The CYP3A5 gene exhibits variable inter-individual expression, which is related to a single-nucleotide polymorphism. Producers of the enzyme possess at least one CYP3A5*1 allele. Knowledge of patients' CYP3A5 genotype, in conjunction with therapeutic drug monitoring (TDM), may aid patient management. Real-time polymerase chain reaction (PCR) was used to genotype the A6986G mutation of the CYP3A5 gene. Specific primers were employed to generate a DNA product, co-amplified with two internal hybridization probes, using a LightCycler. DNA melt curve analysis readily identified the genotypes CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3. Results were confirmed using DNA sequencing with 100% correlation. Genotypes were determined from 263 individuals and compared with the genotypes of a pseudogene CYP3AP1, which is in disequilibrium with CYP3A5. This is a rapid and reliable method for genotyping the CYP3A5 polymorphism which may be used as an important adjunct to the TDM service offered by laboratories to optimize drug prescription.

Clinical outcomes in a randomized controlled study comparing azathioprine and prednisolone versus prednisolone alone in the treatment of severe leprosy type 1 reactions in Nepal.

The ILEP nerve function impairment and reaction research programme (INFIR 2) was a group of clinical trials conducted to identify second-line treatments for severe leprosy type 1 reactions (T1R). This paper presents the clinical results of one of these trials in which azathioprine was used in combination with short-course prednisolone to ascertain if the combination was effective in controlling the symptoms and signs of reaction. Forty patients were alternately assigned to a 12-week treatment with either AP (12 weeks azathioprine at 3mg/kg/d plus 8 week reducing course prednisolone starting at 40mg/d) or P (12-week reducing course prednisolone starting at 40mg/d). Evaluation included serial quantitative clinical assessments. The overall frequency of side effects was similar in both groups. Results show that there was no difference in clinical outcome in the AP and P groups and a similar number of patients in each group required extra prednisolone for worsening clinical features. We conclude that a 12-week course of azathioprine at 3mg/kg/day plus an 8 week reducing course of prednisolone starting at 40mg/d is as effective as a 12 week reducing course of prednisolone starting at 40mg/d and that the combination therapy is well-tolerated in severe leprosy T1R patients.

Detection of IL-13, IL-10, and IL-6 in the leprosy skin lesions of patients during prednisolone treatment for type 1 (T1R) reactions.

This study demonstrates the presence of IL-10 and IL-6, by immunohistochemistry, in the skin lesions of patients with Type 1 reactions. Fifteen patients with Type 1 reaction from Hyderabad, India were included in this study. They were all receiving standardized treatment for Type 1 reactions: a reducing course of daily oral prednisolone for 6 months. Biopsies were taken before treatment and during treatment at weeks 1, 4, and 6 months. IL-13 was observed in the lesions of most patients. By week 4 of treatment, the presence of IL-13, IL-10, and IL-6 in the lesions had decreased significantly. Although some patients showed significant clinical skin sign improvement within one week of therapy, no concomitant decrease or increase in any of the cytokines was observed at this time point. Interestingly, some cytokine activity within the lesions was observed after 6 months of treatment.