College London Hospitals NHS Foundation Research Articles

PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

SummaryBackgroundStatin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.MethodsIn this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.FindingsData were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, −0·01 to 0·08), fasting insulin (0·00%, −0·06 to 0·07), and BMI (0·11 kg/m2, −0·09 to 0·30).InterpretationPCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins.FundingBritish Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.

Are men who are biopsied without prior prostate magnetic resonance imaging getting substandard care?

Are men who are biopsied without prior prostate magnetic resonance imaging getting substandard care?

Editorial introductions

Editorial introductions

Implementation of NICE Clinical Guideline 95 for assessment of stable chest pain in a rapid access chest pain clinic reduces the mean number of investigations and cost per patient

ObjectiveIn 2010, the National Institute for Health and Care Excellence (NICE) in the UK published Clinical Guideline 95 (CG95) advocating risk stratification of patients using ‘CADScore’ to guide appropriate cardiac...

PLD.50 Maternal Request Caesarean Section: 2 NICE Pathways?

BackgroundIn November 2011, the National Institute for Health and Clinical Excellence (NICE) in the UK published clinical guidance on Caesarean Sections. NICE states “For women requesting a CS, if after...

Ambulatory chemotherapy for teenagers and young adults

Ambulatory chemotherapy allows high-dose chemotherapy to be delivered in an outpatient facility with multidisciplinary planning and management. At University College London Hospitals NHS Foundation Trust, this model of care has been successfully applied to a teenage and young adult population. A mobile infusion device, CADD-Solis VIP pump has allowed chemotherapy and supportive therapy administration in the ambulatory setting. Continuous and intermittent therapies have been delivered. Patients attend the ambulatory care unit daily for assessment and treatment set up. Overnight, they reside in nearby accommodation. Patients are educated to self-manage, promoting independence and empowerment; however, they also have 24-hour access to nursing and medical advice. Clear communication and patient education, adopting a multidisciplinary team approach and clear assessment guidance for patients and staff, is essential to make this model of care successful.

A Simple Prognostic Score to Predict Short and Long-Term Survival Following ICU Admission in Critically Ill Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients: Improved Survival Following Reduced Intensity Conditioning

Abstract 146▪▪This icon denotes a clinically relevant abstractTransplant-related complications necessitate intensive care unit (ICU) admission in a significant proportion of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Historically patients requiring ICU admission for transplant related toxicities have fared extremely poorly with very high ICU mortality rates. Although recent reports have indicated improvements in short-term survival for Allo-HSCT patients admitted to ICU there are little data on the subsequent long-term survival of ICU survivors and the impact of reduced intensity conditioning regimens in this cohort of patients. Methods:A retrospective analysis of data collected from 164 consecutive adult Allo-HSCT recipients admitted to ICU (with a total of 214 ICU admissions), at a single centre, University College London Hospitals NHS Foundation Trust (UCLH) between June 1996 and December 2007 (11.5 year study period) was performed. Follow-up of surviving patients was recorded until 31 March 2011. Results:29% of all patients undergoing Allo-HSCT at our centre during the study period required one or more ICU admission. The ICU admission rate was significantly lower for patients undergoing reduced intensity conditioning (RIC) than myeloablative conditioning (17% vs. 38%, p<0.001). The median age of RIC-Allo recipients was significantly older than patients who received myeloablative conditioning (47 vs 36 years, P<0.0001). The most frequent reasons for ICU admission were sepsis (67%) and respiratory failure (55%), not mutually exclusive. Mechanical ventilation (MV) was required in 53% of admissions, inotropic support was required in 47%. Median acute physiology and chronic health score (APACHEII) was 23 (range 0–51). Overall ICU survival for all admissions was 48% (n=214). 35 patients (21%) had more 1 or more ICU admissions. Survival by patient (measured at discharge from final ICU admission) was 32%. ICU survival was significantly better after RIC Allo-HSCT than following myeloablative conditioning (OR 3.27, p=0.023). There was no difference in ICU outcome by stem cell source (sibling vs. unrelated). Patients who did not require ventilatory support (non-invasive ventilation and/or MV) had significantly better ICU outcome (OR 12.7, p<0.001). Multivariate analysis by Cox regression revealed raised urea, inotropic support and MV as independent determinants of death on ICU. Long term survival was significantly better for patients who underwent RIC Allo-HSCT (p=0.0055) (Figure 1). The subsequent long term survival for patients who survived ICU admission was excellent; 1, 2, and 5 year survival rates were 60%, 55%, and 50% respectively (median follow-up 3 years, 7 months).A simple prognostic scoring system has been derived which is predictive of both ICU survival and long term outcome (Table 1). Patients with 2 or more of the following factors: myeloablative conditioning, MV, elevated serum urea, score 1. Patients with <2 of these factors score 0. In our patient population, this binary index has been shown to be predictive of both death on ICU (OR 7.24, p=0.001) or poorer overall survival after ICU discharge (OR 3.04, p=0.01). [Display omitted] Table 1:Prognostic score for prediction of short and long term outcome for allo-HSCT patients admitted to ICU. Score 1 if 2 or more of the following factors are present: Myeloablative conditioning, mechanical ventilation, elevated serum urea.ScoreSurvival to discharge2y OS from discharge5y OS from discharge061%71%65%118%35%26% Conclusion:In this study we report favourable ICU survival following allogeneic HSCT and for the first time report significantly better short and long-term outcome for patients who underwent RIC Allo-HSCT compared to those treated with myeolablative conditioning regimens despite a higher median age in the patients undergoing RIC transplants. For patients surviving ICU admission, subsequent long-term overall survival was excellent at 50% at 5 years, comparing favourably with other critically ill non-surgical patients admitted to ICU. A simple prognostic score has been generated which can be used to predict outcome in critically ill patients admitted to ICU following Allo-HSCT. Disclosures:No relevant conflicts of interest to declare.

Autogenic Training as a behavioural approach to insomnia: a prospective cohort study

Insomnia is commonly associated with chronic health problems. Behavioural and cognitive factors often perpetuate a vicious cycle of anxiety and sleep disturbance, leading to long-term insomnia. National Institute for Health and Clinical Excellence currently recommends behavioural approaches before prescribing hypnotics. Behavioural approaches aim to treat underlying causes, but are not widely available. Research usually includes patients diagnosed with insomnia rather than secondary, co-morbid sleep- related problems. To examine the effectiveness of autogenic training (AT) as a non-drug approach to sleep-related problems associated with chronic ill health. Prospective pre- and post-treatment cohort study. AT centre, Royal London Hospital for Integrated Medicine, University College London Hospitals NHS Foundation Trust. All patients referred for AT from April 2007 to April 2008 were invited to participate. Participants received standard 8-week training, with no specific focus on sleep. Sleep questionnaires were administered at four time points, 'Measure Your Medical Outcome Profile' (MYMOP) and Hospital Anxiety and Depression Scale, before and after treatment. Results before and after treatment were compared. Camden and Islington Community Local Research and Ethics Committee approved the study. The AT course was completed by 153 participants, of whom 73% were identified as having a sleep-related problem. Improvements in sleep patterns included: sleep onset latency (P = 0.049), falling asleep quicker after night waking (P < 0.001), feeling more refreshed (P < 0.001) and more energised on waking (P = 0.019). MYMOP symptom, well-being, anxiety and depression scores significantly improved (all P < 0.001). This study suggests that AT may improve sleep patterns for patients with various health conditions and reduce anxiety and depression, both of which may result from and cause insomnia. Improvements in sleep patterns occurred despite, or possibly due to, not focusing on sleep during training. AT may provide an approach to insomnia that could be incorporated into primary care.

Polyp Detection is Improved by Megapixel White Light High Resolution Colonoscopy in the UK National Bowel Cancer Screening Program

Introduction Colorectal cancer (CRC) is one of the most common cancers worldwide. Detection of CRC at an early stage, as well as detection and removal of polyps is likely to decrease mortality from the disease. Colonoscopy is established as the gold standard for identification of CRC and polyps and accuracy of the procedure is therefore very important. The UK bowel cancer screening program has been established to reduce deaths from CRC using colonoscopy for patients screened positive by faecal occult blood tests. The authors aim to investigate whether there were differences in performance between standard high resolution colonoscopy system (Olympus Lucera) with a megapixel high resolution system (PentaxHiLine) in the National UK Bowel Cancer Screening Program and in particular polyp detection rates. Methods All patients undergoing colonoscopy in the bowel cancer screening program at University College London Hospitals NHS Foundation Trust between August and November 2009 were included in this prospective study. Bowel cancer screening colonoscopies are performed in our unit with the Olympus Lucera series colonoscopes (CF-Q260DL colonoscopes and CLV 260-SL processor) but during the study period, one screening list was performed with Pentax HiLine colonoscopes (EC-3890i). A specialist bowel cancer screening nurse collected data on completeness of insertion to caecum or terminal ileum, duration of insertion and withdrawal of colonoscope and total length of procedure in real time. In addition the nurse noted the amount of sedation used, the level of conscious sedation (awake, drowsy, asleep) and degree of discomfort suffered by the patient during the procedure (minimal, mild, moderate, severe using nurse evaluated score in line with the National Bowel Cancer Screening standards). Results Data was collected for 269 procedures performed by 5 colonoscopists over 3 months. Adenoma detection rate was significantly higher in the Pentax group (median 1 vs 0 for Olympus, χ 2 test for trend p=0.01). Most extra polyps detected were flat or sessile adenomas with low grade dysplasia. There were no differences in procedure duration, caecal intubation rates, level of consciousness or sedation use. Mild discomfort was more common in the Pentax group but patients did not suffer more moderate or severe discomfort. Conclusion This study demonstrates that higher definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve the outcomes of the Bowel Cancer Screening Program.

Polyp detection is improved by megapixel white light high resolution colonoscopy in the UK national bowel cancer screening program

IntroductionColorectal cancer (CRC) is one of the most common cancers worldwide. Detection of CRC at an early stage, as well as detection and removal of polyps is likely to decrease...

A bereavement and communication study day for midwives

Following the loss of a baby, women and their families have particular needs. As midwives are the main professional group present at this time, they need to support women through the process. However, it may be relatively rare for midwives to encounter bereavement, and so it is important to ensure that competency is maintained in this area. This has been demonstrated by an increasing demand for additional training from midwives, which led to a bereavement and communication study day within the University College London Hospitals NHS Foundation Trust. The study day explored midwives' and women's personal experiences and considered the implications for practice.

Using ActivHeal®&gt; dressings in a London teaching hospital: a cost analysis

Lower-cost 'generic' wound dressings are now available in the dressing categories of foams, films, alginates, gels and hydrocolloids. This offers the possibility of achieving significant financial savings while retaining good clinical standards of wound care. To test the potential for cost saving in a typical London teaching hospital, the ActivHeal range of dressings was substituted for normal 'branded' dressings over a 3-month period, during which dressing cost and clinical effectiveness were assessed. The result was an equivalent yearly cost saving of pound55 221 (54%), with retention of performance standards across the dressing range. Two years after the trial, wards in University College London Hospitals NHS Foundation Trust continue to benefit from significant annual cost savings on dressings by using the ActivHeal range of products, while maintaining a high standard of clinical care.

Coming late to motherhood: a workshop for professionals

Midwives and obstetricians at University College London Hospitals NHS Foundation Trust (UCLH) provide care for a significant number of women who are of a higher maternal age. A bid was successful and funding obtained for a workshop. The grant was a University College London (UCL) Futures Grant awarded for a workshop series on older women in the Institute for Women's Health. This workshop aimed at increasing knowledge and awareness in this under-researched area of care. The multidisciplinary team met together. Users also attended as both participants and within the audience. Experts from various disciplines in the area presented the many issues faced by pregnant women who are 35 years old and more.

After action reviews: a new model for learning

University College London Hospitals NHS Foundation Trust is committed to developing a learning culture for its staff and, to achieve this, the organisation recently developed the after action review (AAR) model as a way for people involved in specific incidents to explore what happened and what they have learned. This article explains the concept of AAR and uses case studies to illustrate how it can improve patient care.

Benign Prostatic Obstruction and Parkinson's Disease—Should Transurethral Resection of the Prostate be Avoided?

According to the literature transurethral resection of the prostate in patients with Parkinson's disease has an increased risk of postoperative urinary incontinence. However, this conclusion might have been reached because some patients with multiple system atrophy incorrectly diagnosed as Parkinson's disease were included in these reports. Therefore, we investigated the outcome of transurethral prostate resection in patients with a secure neurological diagnosis of Parkinson's disease. A total of 23 patients with Parkinson's disease who underwent transurethral prostate resection for benign prostatic obstruction were evaluated retrospectively. Subsequent neurological developments in patients were followed, ensuring that those with multiple system atrophy had not been included in analysis. At transurethral prostate resection median patient age was 73 years, median duration of Parkinson's disease before the resection was 3 years, and median Hoehn and Yahr scale was 2. Of the 14 patients with a preoperative indwelling urinary catheter transurethral prostate resection restored voiding in 9 (64%) and only 5 (36%) required catheterization postoperatively. Of the 10 patients with preoperative urge urinary incontinence, continence was restored in 5 and improved in 3 following transurethral prostate resection. There were no cases of de novo urinary incontinence after transurethral prostate resection. At a median postoperative followup of 3 years transurethral prostate resection was successful in 16 of the 23 patients (70%). Transurethral prostate resection for benign prostatic obstruction in patients with Parkinson's disease may be successful in up to 70% and the risk of de novo urinary incontinence seems minimal. Thus, Parkinson's disease should no longer be considered a contraindication for transurethral prostate resection provided that preoperative investigations including urodynamic assessment indicate prostatic bladder outlet obstruction.

Peripheral vascular disease

Contributed by Mr Stephen G E Barker, senior lecturer in surgery, University College London and honorary consultant vascular surgeon, University College London Hospitals NHS Foundation Trust

A22 Calculation of split renal function from contrast enhanced multidetector CT: comparison with renal scintigraphy

aDepartment of Radiology, Luton and Dunstable Hospital NHS Trust bDepartment of Radiology, University College London Hospitals NHS Foundation Trust, UK Abstracts for the Autumn Meeting of the British Nuclear Medicine Society Cambridge, UK, 4–5 September 2006

Role modelling

Samantha Philpott and Philomena Corrigan of the university college London hospitals NHS foundation trust describe the difficulties and responsibilities of being a model nurse