Gerard Savage

Evidence of prostate cancer screening in a UK region.

To examine the pattern of use of prostate‐specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer.

The finding of reduced estimated glomerular filtration rate is associated with increased mortality in a large UK population

BACKGROUND CKD as defined by KDIGO/KDOQI has been shown to affect ~ 8.5% of the UK population. The prevalence of CKD in the UK is similar to that in the USA, yet incident dialysis rates are dramatically different. This retrospective cohort study investigates the association between reduced kidney function and mortality in a large UK population. METHODS All serum creatinine results covering Northern Irelands 1.7 million population were collected between 1 January 2001 and 31 December 2002. Estimated glomerular filtration rates (eGFR) were calculated for all serum creatinine measurements using four-variable MDRD equation (IDMS aligned). Patients were followed up for both all-cause and cardiovascular mortality data until the end of December 2006. Patients on renal replacement therapy were excluded. Subgroup analysis in the 75,345 subjects enrolled within a parallel primary care study permitted additional survival analysis with adjustment for traditional cardiovascular risk factors. RESULTS A total of 1,967,827 serum creatinine results from 533,798 patients were collected. During the period of follow-up, 59,980 deaths occurred. In multivariate survival analysis, using eGFR as a time-varying covariate, a graded association between CKD (defined by eGFR) and all-cause mortality was identified. Compared with participants with an eGFR of > 60 mL/min/1.73 m(2), the adjusted hazard ratios (and 95% confidence intervals) for participants with an eGFR of 45-59 mL/min/1.73 m(2) was 1.02 (0.99-1.04), an eGFR of 30-44 mL/min/1.73 m(2) was 1.44 (1.40-1.47), an eGFR of 15-29 mL/min/1.73 m(2) was 2.12 (2.05-2.20) and an eGFR of < 15 mL/min/1.73 m(2) was 3.46 (3.24-3.70). Significantly, increased all-cause mortality was associated with an eGFR < 45 mL/min/1.73 m(2) following adjustment for age and gender. The association between cardiovascular mortality and reduced renal function continued to be significant for participants with an eGFR of 45-65 mL/min/1.73 m(2). Subgroup analysis in 75,345 individuals with more detailed clinical information available confirmed this association following adjustment for traditional cardiovascular risk factors in addition to age and gender. CONCLUSIONS This study demonstrates a graded association between reduced renal function as represented by eGFR and mortality in a UK population. The all-cause and cardiovascular mortality risk increases sharply when estimated GFR falls < 45 mL/min/1.73 m(2). The association between an eGFR measured between 45 and 65 mL/min/1.73 m(2) and cardiovascular mortality persists in this cohort and highlights the ongoing uncertainty in accurately categorizing renal dysfunction.

The SWAT (study within a trial) programme; embedding trials to improve the methodological design and conduct of future research.

Researchers and trialists face many uncertainties when designing and conducting research. Embedded methodology studies can help to resolve these. However, despite hundreds of thousands of trials, there are probably only a few hundred studies assessing the effects of different methods for doing this research. The concept of the SWAT (Study Within A Trial) programme is to aid the development of such research by increasing awareness of, and stimulating interest in the need for this research and providing a framework and resource to inspire and generate ideas, and to store, disseminate and modify such research. The programme was established as part of the development of an All-Ireland Hub for Trials Methodology Research in collaboration with the Medical Research Councils Network of Hubs in the UK and the Global Health Network. It will facilitate this research into research. Each SWAT comprises of simple, one or two page protocols and, as of April 2015, 19 different SWAT outlines have been registered. This presentation will detail the SWAT concept, and describe the core outline which consists of the following sections: background, intervention, comparator, allocation, primary outcomes, secondary outcomes, analysis, possible problems, likely costs, publications, and version information. The SWAT website will be available to view, and examples of completed SWATs will be shown. The presentation should stimulate ideas for future SWAT, and encourage researchers to see how they might maximize the impact of embedding research into research, leading to improvements in the design of future clinical trials and other studies.

Are gatekeepers to renal services referring patients equitably

Objective: Patients with chronic kidney disease (CKD) benefit from specialist interventions to retard progression of renal failure and prevent cardiovascular events. Certain patient groups have poor access to specialist renal services when dialysis is required. This study used a population-based laboratory database to investigate access to and timeliness of referral to renal specialists relatively early in the course of the disease. Methods: All tests for serum creatinine and haemoglobin (Hb) A1c in Northern Ireland in a two-year period (2001 and 2002) were retrieved for 345,441 adults. Of these, 16,856 patients had at least one serum creatinine level above 150 μmol/L in 2001 not deemed to be due to acute renal failure (crude prevalence 1.42%). This cohort was followed until the end of 2002 and the differences in the time to referral to a specialist were assessed using Coxs proportional hazards regression. Results: Diabetic patients, older patients and those living in deprived areas were significantly more likely to have serum creatinine testing, compared with non-diabetic, younger and those living in more affluent areas. Delays in referral to renal specialists for patients with raised serum creatinine levels were significantly shorter among diabetic patients, women, younger individuals, those living in rural areas, those living close to renal centres and those living in deprived areas. Overall, only 19% of diabetic patients and 6% of non-diabetic patients who had CKD had seen a renal specialist within 12 months of their index creatinine test. Conclusion: Contrary to other diseases, disadvantaged patients do not seem to be under-investigated for renal disease compared with their more affluent neighbours and are generally referred earlier for specialist assessment. However, the absolute rate of timely specialist assessment is low. Recent changes in referral criteria for CKD will result in more referrals and will have serious resource implications. Opportunities for health gain among patients with declining renal function are being missed, particularly among the old and those living furthest from specialist centres.

Late referral for assessment of renal failure

It has been recommended that adult patients with a serum creatinine above 150 μmol/l should be referred to a nephrologist for specialist assessment. This study ascertained all patients in Northern Ireland with creatinine above this concentration in 2001 (n = 19 286 ) to see if this triggered referral within the subsequent year. After exclusion of those who were already known to a nephrologist and those who had acute renal failure, it was found that younger patients and diabetic patients were more likely to be referred. There was no difference in referral rates between male and female patients. However, only 6.5% of all non-diabetic subjects and 19% of diabetic patients were referred within 12 months after a first increased serum creatinine test.

Identifying additional patients with diabetic nephropathy using the UK primary care initiative

Diabet. Med. 27, 1372–1378 (2010)

Lithium usage and renal function testing in a large UK community population; a case–control study ☆ ☆☆ ★ ★★

OBJECTIVE This study investigates the prevalence of lithium use, monitoring practice and associated effects on renal function in a large UK community sample. METHOD A large population-based renal function database was cross-referenced with a general practitioner database of 404,673 patients. The renal function of patients prescribed lithium during the 2-year period was compared with that of matched controls. The renal monitoring patterns of these cases were investigated in a naturalistic observational study. Data underwent parametric testing - continuous variables by analysis of variance, with appropriate adjustment, and categorical outcomes by χ(2) testing. Block analysis of variance was undertaken on case-control data. RESULTS A total of 422 patients in the database were prescribed lithium. Renal function monitoring in accordance with published guidelines occurred in 69% of patients. Patients taking lithium had a significantly higher serum creatinine (5.8 μmol/L, P<.001) and lower glomerular filtration rate (5.9 ml/min, P<.001) when compared to matched controls. CONCLUSIONS This is the first study carried out in a large community sample. Lithium remains widely prescribed in the community setting. The study confirms that lithium has a statistically and clinically significant negative effect on renal function. Despite published guidelines and recognition of the importance of serial measurements, monitoring of renal function is inconsistent.

Process evaluation for OptiBIRTH, a randomised controlled trial of a complex intervention designed to increase rates of vaginal birth after caesarean section

BackgroundComplex interventions encompassing several interconnecting and interacting components can be challenging to evaluate. Examining the underlying trial processes while an intervention is being tested can assist in explaining why an intervention was effective (or not). This paper describes a process evaluation of a pan-European cluster randomised controlled trial, OptiBIRTH (undertaken in Ireland, Italy and Germany), that successfully used both quantitative and qualitative methods to enhance understanding of the underlying trial mechanisms and their effect on the trial outcome.MethodsWe carried out a mixed methods process evaluation. Quantitative and qualitative data were collected from observation of the implementation of the intervention in practice to determine whether it was delivered according to the original protocol. Data were examined to assess the delivery of the various components of the intervention and the receipt of the intervention by key stakeholders (pregnant women, midwives, obstetricians). Using ethnography, an exploration of perceived experiences from a range of recipients was conducted to understand the perspective of both those delivering and those receiving the intervention.ResultsEngagement by stakeholders with the different components of the intervention varied from minimal intensity of women’s engagement with antenatal classes, to moderate intensity of engagement with online resources, to high intensity of clinicians’ exposure to the education sessions provided. The ethnography determined that, although the overall culture in the intervention site did not change, smaller, more individual cultural changes were observed. The fidelity of the delivery of the intervention scored average quality marks of 80% and above on repeat assessments.ConclusionNesting a process evaluation within the trial enabled the observation of the mode of action of the intervention in its practice context and ensured that the intervention was delivered with a good level of consistency. Implementation problems were identified as they arose and were addressed accordingly. When dealing with a complex intervention, collecting and analysing both quantitative and qualitative data, as we did, can greatly enhance the process evaluation.Trial registrationCurrent Controlled Trials Register, ISRCTN10612254. Registered on 3 April 2013.

The Effects of Anti-Hypertensive Drugs Evaluated Using Markov Modelling for Northern Ireland Chronic Kidney Disease Patients

The aim of this paper is to use Markov modelling to investigate survival for particular types of kidney patients in relation to their exposure to anti-hypertensive treatment drugs. In order to monitor kidney function an intuitive three point assessment is proposed through the collection of blood samples in relation to chronic kidney disease for Northern Ireland patients. A five state Markov model was devised using specific transition probabilities for males and females over all age groups. These transition probabilities were then adjusted appropriately using relative risk scores for the event death for different subgroups of patients. The model was built using TreeAge software package in order to explore the effects of anti-hypertensive drugs on patients.