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Proceedings From the Symposium on Kidney Disease in Older People: Royal Society of Medicine, London, January 19, 2017

People are living longer. On the whole, they have healthier lives and many of the problems previously seen at a younger age now appear in their later years. Kidneys, like other organs, age, and kidney disease in the aged is a prime example. In the United Kingdom, as in other developed countries, the prevalence of end stage kidney disease is highest in the 70- to 79-year-old age group. There are many older people who require renal replacement and are now considered for dialysis. While older patients with end-stage renal disease invariably aspire for a better quality of life, this needs a specialized approach and management. In January 2017, the Royal Society of Medicine held a seminar in London on “Kidney Disease in Older People” with presentations from a multidisciplinary body of experts speaking on various aspects of kidney problems in this age group and its management. The objectives were to increase awareness and improve the understanding of nephrology in the context of geriatric medicine but also geriatrics in its interface with nephrology, especially in the area of chronic kidney disease

Improving completeness of electronic problem lists through clinical decision support: a randomized, controlled trial

Background: Accurate clinical problem lists are critical for patient care, clinical decision support, population reporting, quality improvement, and research. However, problem lists are often incomplete or out of date. Objective: To determine whether a clinical alerting system, which uses inference rules to notify providers of undocumented problems, improves problem list documentation. Study Design and Methods: Inference rules for 17 conditions were constructed and an electronic health record-based intervention was evaluated to improve problem documentation. A cluster randomized trial was conducted of 11 participating clinics affiliated with a large academic medical center, totaling 28 primary care clinical areas, with 14 receiving the intervention and 14 as controls. The intervention was a clinical alert directed to the provider that suggested adding a problem to the electronic problem list based on inference rules. The primary outcome measure was acceptance of the alert. The number of study problems added in each arm as a pre-specified secondary outcome was also assessed. Data were collected during 6-month pre-intervention (11/2009–5/2010) and intervention (5/2010–11/2010) periods. Results: 17,043 alerts were presented, of which 41.1% were accepted. In the intervention arm, providers documented significantly more study problems (adjusted OR=3.4, p<0.001), with an absolute difference of 6,277 additional problems. In the intervention group, 70.4% of all study problems were added via the problem list alerts. Significant increases in problem notation were observed for 13 of 17 conditions. Conclusion: Problem inference alerts significantly increase notation of important patient problems in primary care, which in turn has the potential to facilitate quality improvement

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p&lt;0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p&lt;0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p&lt;0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Health and population effects of rare gene knockouts in adult humans with related parents.

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.The study was funded by the Wellcome Trust (WT102627 and WT098051), Barts Charity (845/1796), Medical Research Council (MR/M009017/1). This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber. Core support for Born in Bradford is also provided by the Wellcome Trust (WT101597). V.N. was supported by the Wellcome Trust PhD Studentship (WT099769). D.G.M. and K.K. were supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM104371. E.R.M. is funded by NIHR Cambridge Biomedical Research Centre. H.H. is supported by awards to establish the Farr Institute of Health Informatics Research, London, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, NIHR, National Institute for Social Care and Health Research, and Wellcome Trust.This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via https://doi.org/10.1126/science.aac862

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy