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As projections of climate change become more detailed and sophisticated, analysing the effects of these projections on, for example, building performance will become more complex. This study, as part of the Low Carbon Futures project, proposes a method for integrating the latest UK Climate Projections 2009, which are probabilistic in nature, into dynamic building simulation calculations. This methodology offers the possibility that, in an analysis of overheating in buildings, it will be viable for a building designer to assess future thermal comfort of a building in a probabilistic way, with various climate scenarios informing a risk analysis of whether that building will become unsuitable as a working/living environment. To reduce the computational requirements of such an analysis, a series of statistical manipulations and approximations are proposed that serve to reduce substantially the amount of computation that would otherwise be necessary when using such climate projections. The resulting tool, which in essence captures the behaviour of complex simulation models using linear filtering techniques and regression, is successfully validated against results obtained from building simulation software results for a domestic building case-study, including versions of the building with specific adaptation scenarios applied that might offset the predicted overheating. [ABSTRACT FROM AUTHOR]

Despite the temperate climate, cooling loads in UK non-domestic buildings (specifically offices) have a highly significant effect on the energy use of urban areas. Recent summer heatwaves (as seen in 2005) caused blackouts in areas of London, where the requirement for cooling resulted in an electrical demand that exceeded the capacity. With summer temperatures predicted to rise, this problem is likely to be exacerbated, and the need to mitigate for such a scenario is vital. Passive and low-energy cooling techniques can play an important role in reducing official electrical demands. However, the more fundamental problem relates to the internal heat gains being generated from, in particular, IT equipment and lighting. For a country such as the UK, cooling systems in offices (and other non-domestic buildings) only exist at all due to these gains. Through the use of energy management and technologies that might be available by 2030, internal equipment gains can be reduced such that the requirements on the office cooling system are completely different, and the likelihood of a passively cooled office (or low-carbon office) greatly increased. This study thus proposes an approach for reducing office cooling loads for a UK climate, using a defined exemplar London office building to demonstrate the effect of IT equipment and lighting on cooling for the existing buildings. In addition, the effect of fabric changes and thermal adaptation of occupants (for a warmer future climate) is estimated. Finally, taking a ‘make tight, ventilate right’ approach (i.e. reducing infiltration and using mechanical ventilation appropriately) is looked at with regards to cooling loads and, specifically, the effectiveness of night-time ventilation. [ABSTRACT FROM PUBLISHER]

Abstract: A typical UK office is used as an exemplar for office energy use in the UK. The effect of replacing existing boilers and air-conditioning systems with air-source heat pumps (ASHPs) is investigated for a “current” version of the office, with typical equipment/lighting usage, fabric and internal gains, and also for a “2030” office, where fabric is improved, equipment/lighting made more efficient and, as a result, internal gains reduced. The ASHPs, as a potential carbon-saving technology, performs slightly differently for the two office scenarios. Furthermore, after removing the boiler, it is found to be important whether electric hot water or gas hot water point-of-use heaters are adopted with the ASHPs (assuming that the existing boiler would not be used if the ASHPs is satisfying all space heating requirements). This can be the difference between ASHPs reducing and increasing the carbon emissions of the office. Finally, the carbon intensity of the grid has a large effect on the success of ASHPs technology. This is quantified through a sensitivity analysis, indicating the external conditions for which ASHPs might reduce CO2 emissions for office buildings. The results suggest that an ASHPs has the potential to reduce CO2 emissions for certain conditions, but should not be seen as a guaranteed low-carbon technology for all scenarios. As well as assessing the ASHPs as a carbon-saving technology, potential economic benefits are also estimated based on running costs and predicted reduction in energy bills. [Copyright &y& Elsevier]

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites. [ABSTRACT FROM AUTHOR]

Evaluates the effect on resource savings and on the incidence of invasive cancer of strategies for the early withdrawal from the screening programmes of women at low risk of cervical cancer. Mathematical model used; Related studies; Results and discussion.

The article discusses the history of trade between manufacturers of wool textiles in Europe and Japan. The commercial treaties signed in 1858 by Japan with several countries, such as Great Britain and the U.S., allowed foreign merchant houses access to the three treaty ports of Kanagawa, Nagasaki and Hakodate. The Japanese woollen industry became the single most important foreign market for the British industry. In the mid-1920s, Great Britain exported on average over 88 million square yards of woollen cloth and over 5 million square yards of worsted cloth to Japan.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in the UK are common and associated with significant morbidity and mortality. Vancomycin is the usual first-line therapy. However, vancomycin treatment of BSIs due to MRSA strains with vancomycin MICs of 1–2 mg/L is successful in <10% of cases. No consensus exists on when to use newer agents, particularly when vancomycin MICs are >1 mg/L. We therefore surveyed UK practices of the management of MRSA BSIs due to isolates with increased vancomycin MICs. [ABSTRACT FROM PUBLISHER]

Introduction Pulmonary endarterectomy (PEA) is the treatment of choice for patients with proximal chronic thromboembolic pulmonary hypertension (CTEPH). The UK has a single centre performing this operation and the program became nationally funded since 2000. Patients are referred from seven specialist pulmonary hypertension centres. Method All 625 patients treated with PEA from 2000 to 2010 were mapped according to their home postcode at the time of PEA surgery. Primary care trusts (PCT's) were assigned from these home postcodes. The incidence rate of each PCT and overall incidence were analysed. Map info software was used to generate the referral maps. Results The new patient incidence ranges from no referrals in 123 PCT's in 2000-2002 to 90 in 2008-2010. The most recent period shows highest referral rates for PEA. From our PEA data mapping analysis we have calculated that the incidence of operated patients was 0.4 million population in 2000 (n=22) and 2 per million population in 2010 (n=122). Conclusion There has been a fivefold increase in PEA activity in the UK over the last decade. The analysis of our data are limited to surgical cases. The current incidence of PEA in the UK is already higher than historical estimation of the incidence of all CTEPH (0.1-0.5/million, Fedullo, N Engl J Med 2001). Since 30% of patients with CTEPH have distal disease distribution and some patients with proximal CTEPH do not proceed to surgery due to choice or comorbidities, the overall incidence of CTEPH is likely to be significantly higher than 2 per million/year and higher than previously suspected. [ABSTRACT FROM AUTHOR]

The 2020 ISHLT consensus statement recommends coronary angiography in potential heart donors with risk factors for coronary disease (CAD), including those aged >40 yrs. Angiography is not commonly available for donors in the UK. At retrieval, donor hearts without palpable CAD are offered for transplantation. The accuracy of this in detecting underlying CAD is unreliable. We examined the incidence of occult donor transmitted (dt) CAD and its impact on long term survival in our heart transplant (HTx) recipients. All adult patients undergoing HTx Jan'08 - Dec'18, who had early coronary angiography post HTx by left heart catheterization or computed tomography included. Angiograms were retrospectively graded by 2 observers, according to ISHLT classification of CAV. Significant dtCAD was defined as evidence of CAV grade 2 or 3 or a focal lesion >50% in a main artery at first angiographic assessment. Over the 11-year period 389 HTx performed, 302 met inclusion criteria. Mean recipient age 48.8 yrs, 77.8% male, donor age 38.2 yrs, 64.6% male, BMI 26.6 kg/m2. 28 recipients (9%) had evidence of dtCAD. This was associated with a significant reduction in long term survival (Figure 1, p=0.002). No significant difference in dtCAD in hearts from donors >40 yrs vs donors ≤ 40 yrs (10.3 % vs 8.3%, p=0.99). In donors >40 yrs, neither a history of smoking (p=0.18), diabetes (p=0.36) or hypertension (p=0.55) were associated with significant CAD in isolation. The presence of 2 or more of the aforementioned risk factors in those > 40 yrs was associated with a higher incidence of dtCAD (25.0% vs 8.0% p=0.05). In this single centre cohort, dtCAD was associated with a reduction in long-term conditional survival following HTx. Donor age of >40 yrs alone was not predictive of significant dtCAD.Donor age >40 along with a history of 2 or more of hypertension, smoking or diabetes was found to be predictive of a higher risk of dtCAD. In such donors, surgical palpation alone may be insufficient to exclude significant CAD. [ABSTRACT FROM AUTHOR]

Purpose The demand for heart transplantation has increased by 162% in the United Kingdom over the last decade. In an attempt to address both wait list mortality and prolonged waiting times, a programme of DCD heart transplantation was implemented at Royal Papworth Hospital in March 2015. We report the early outcomes of the first 50 DCD heart transplants and compare them to a matched cohort of donation after brain death (DBD) heart transplants. Methods DCD hearts were retrieved either by; Normothermic Regional Perfusion followed by ex-situ heart perfusion (NRP-ESHP), NRP followed by cold storage (NRP-CS) or Direct Procurement and Perfusion using ESHP alone (DPP-ESHP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation whilst DPP hearts were removed directly. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics was used as a comparison group. All DBD hearts were transported using static cold storage. Outcome measures for this study included 30 day survival as well post transplant inotrope dependence, mechanical support, initial cardiac performance, ventilator duration, intensive care duration and length of hospital stay. Results From 1st March 1 2015 to 10th October 50 DCD heart transplants were performed at our institute. Sixteen DCD hearts were transplanted following (NRP-ESHP), 32 hearts following (DPP-ESHP) and 2 hearts following (NRP-CS). The 30-day survival post transplant was 100% in both DCD and DBD groups. All other outcome variables were comparable between groups with the exception of Dopamine reliance post transplant, table 1. Values are median (IQR) or n (%) Conclusion After 50 DCD heart transplants, the results continue to show that DCD heart transplantation can be performed safely with comparable early outcomes to those achieved with DBD heart transplantation. [ABSTRACT FROM AUTHOR]

Purpose: The detection of congenital heart disease (CHD) before neonatal surgery is crucial for anaesthetic and perioperative management. There are no established criteria for pre-operative echocardiography in neonates. We aimed to survey current practice in the United Kingdom and evaluate the reliability of antenatal screening and postnatal clinical assessment in detecting CHD before surgery., Method: A 9-point questionnaire was sent to all paediatric surgical centres in the United Kingdom to assess their practice. Subsequently, a single-centre retrospective review of all neonatal surgery over 5 years (2015-2020) was conducted in our tertiary paediatric/neonatal hospital. Data included pre-operative clinical assessment, performance of chest radiograph and echocardiography. Indications for echocardiography were categorised and assessed using sensitivity, specificity, positive predictive value and negative predictive value., Results: All 26 paediatric surgical centres responded to our survey. 23/26 (88.5%) did not have established criteria or guidelines for pre-operative echocardiography. There was a large variation in which surgical conditions required a pre-operative scan and whether a normal clinical examination was considered sufficient to not require one. For the retrospective review, 454 patients were identified. There were 40 cases with CHDs (8.8%), 13 were classed as major or moderate. Indications for echocardiography were categorised into abnormal foetal cardiac screening, medical/surgical conditions associated with CHD and an abnormal cardiorespiratory examination. Sensitivity, specificity, positive predictive value and negative predictive value for major and moderate CHD were 46%, 99%, 67%, 98% for abnormal foetal screening, 46%, 97%, 35%, 98% for associated medical conditions, 62%, 66%, 6%, 98% for associated surgical conditions, and 100%, 66%, 9%, 100% for abnormal clinical examination., Conclusion: The use of pre-operative echocardiography in neonates is not standardised across the UK. The results from our cohort demonstrate that foetal echocardiography is not sufficient to capture all major and moderate CHDs, but the absence of abnormal clinical examination is highly reliable in ruling out them out. Specifying a list of medical/surgical of conditions associated with CHD warranting pre-operative echocardiography may improve yield, but this depends on the availability of resources and expertise., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported., Methods: This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum., Results: From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p = 0.0006), and DCD hearts in the pre pilot era, (17%, p = 0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p = 0.13) nor hospital stay (28 DCD vs 27 DBD days, p = 0.46)., Conclusion: During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors., Competing Interests: Disclosure The authors have no conflicts of interest to declare. This research was funded by the National Health Service Blood and Transplant and National Health Service England., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Aims: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken., Methods and Resuts: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality., Conclusion: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery., Competing Interests: Conflict of interest: B.R.C. has received speaking fees from Abbott Vascular. P.M. has provided expert testimony and worked as a speaker for Edwards Lifesciences. J.B. has worked as a proctor for Abbott Vascular. M.S.T. has worked as a consultant and received educational grants from Occlutech. He has worked as a consultant and proctor for Abbott Vascular. D.B.N. has worked as a proctor for Abbott Vascular. D.H.-S. has received travel support and worked as a proctor for Abbott Vascular and Boston Scientific; he has received consulting fees and participated in a data and safety monitoring board for Abbott Vascular. M.A.M. has received non-restrictive educational grants from Abbott Vascular and Terumo, and worked as a consultant for Daiichi Sankyo and Terumo. P.A.C. has worked as a proctor for Abbott Vascular, Gore Medical and Occlutech., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program., Methods: This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival., Results: During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30 days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84)., Conclusions: DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: High-dose tranexamic acid (TXA) can cause seizures in patients who have undergone pulmonary endarterectomy (PTE). Seizures secondary to TXA will resolve once the drug is excreted from the body, and the patients do not have to be on long-term anticonvulsants. The aim of the study is to find out if medication review in the hospital has led to deprescribing of anticonvulsants for TXA-associated seizures on discharge from the critical care unit (CCU) and hospital., Methods: This is a single-centre retrospective study conducted at a tertiary cardiothoracic hospital between 2012 and 2017. The inclusion criteria consisted of all adult patients who have undergone PTE surgery. Patients who were started on anticonvulsants preoperatively or postoperatively for seizures secondary to organic causes were excluded., Results: A total of 933 patients underwent PTE from January 2012 to August 2017. 25 patients had TXA-related seizures postoperatively and were started on anticonvulsant therapy, giving an incidence of 2.7%. 15 patients were discharged from the CCU without anticonvulsants. A further three patients had their anticonvulsants deprescribed in the ward before being discharged from the hospital., Conclusion: Deprescribing of anticonvulsants after benign seizures secondary to high-dose TXA is facilitated by verbal and written handover, which can be improved in our hospital. A detailed handover summary, as well as a discharge letter with clearly defined instructions for drug review, is needed to make deprescribing a more robust process., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antimicrobial resistance is driven by the overuse of antibiotics. This study aimed to develop and validate clinical prediction models for the risk of infection-related hospital admission with upper respiratory infection (URTI), lower respiratory infection (LRTI) and urinary tract infection (UTI). These models were used to investigate whether there is an association between the risk of an infection-related complication and the probability of receiving an antibiotic prescription., Methods: The study used electronic health record data from general practices contributing to the Clinical Practice Research Datalink (CPRD GOLD) and Welsh Secure Anonymised Information Linkage (SAIL), both linked to hospital records. Patients who visited their general practitioner with an incidental URTI, LRTI or UTI were included and followed for 30 days for hospitalisation due to infection-related complications. Predictors included age, gender, clinical and medication risk factors, ethnicity and socioeconomic status. Cox proportional hazards regression models were used with predicted risks independently validated in SAIL., Results: The derivation and validation cohorts included 8.1 and 2.7 million patients in CPRD and SAIL, respectively. A total of 7125 (0.09%) hospital admissions occurred in CPRD and 7685 (0.28%) in SAIL. Important predictors included age and measures of comorbidity. Initial attempts at validating in SAIL (i.e. transporting the models with no adjustment) indicated the need to recalibrate the models for age and underlying incidence of infections; internal bootstrap validation of these updated models yielded C-statistics of 0.63 (LRTI), 0.69 (URTI) and 0.73 (UTI) indicating good calibration. For all three infection types, the rate of antibiotic prescribing was not associated with patients' risk of infection-related hospital admissions., Conclusion: The risk for infection-related hospital admissions varied substantially between patients, but prescribing of antibiotics in primary care was not associated with risk of hospitalisation due to infection-related complications. Our findings highlight the potential role of clinical prediction models to help inform decisions of prescribing of antibiotics in primary care.

Objective: Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) managed medically has a poor prognosis. Balloon pulmonary angioplasty (BPA) offers a new treatment for inoperable patients. The national BPA service for the UK opened in October 2015 and we now describe the treatment of our initial patient cohort., Methods: Thirty consecutive, inoperable, anatomically suitable, symptomatic patients on stable medical therapy for CTEPH were identified and offered BPA. They initially underwent baseline investigations including Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) quality of life (QoL) questionnaire, cardiopulmonary exercise test, 6 min walk distance (6MWD), transthoracic echocardiography, N-terminal probrain natriuretic peptide (NT pro-BNP) and right heart catheterisation. Serial BPA sessions were then performed and after completion, the treatment effect was gauged by comparing the same investigations at 3 months follow-up., Results: A median of 3 (IQR 1-6) BPA sessions per patient resulted in a significant improvement in functional status (WHO functional class ≥3: 24 vs 4, p<0.0001) and QoL (CAMPHOR symptom score: 8.7±5.4 vs 5.6±6.1, p=0.0005) with reductions in pulmonary pressures (mean pulmonary artery pressure: 44.7±11.0 vs 34.4±8.3 mm Hg, p<0.0001) and resistance (pulmonary vascular resistance: 663±281 vs 436±196 dyn.s.cm -5 , p<0.0001). Exercise capacity improved (minute ventilation/carbon dioxide production: 55.3±12.2 vs 45.0±7.8, p=0.03 and 6MWD: 366±107 vs 440±94 m, p<0.0001) and there was reduction in right ventricular (RV) stretch (NT pro-BNP: 442 (IQR 168-1607) vs 202 (IQR 105-447) pg/mL, p<0.0001) and dimensions (mid RV diameter: 4.4±1.0 vs 3.8±0.7 cm, p=0.002). There were no deaths or life-threatening complications and the mild-moderate per-procedure complication rate was 10.5%., Conclusions: BPA is safe and improves the functional status, QoL, pulmonary haemodynamics and RV dimensions of patients with inoperable CTEPH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A series of infection control measures were introduced at the University Hospitals of Leicester NHS Trust in 2006-2007 to reduce the incidence of Clostridium difficile infection., Aim: The aim of this study was to assess the impact of these measures on the incidence of C. difficile and to record the associated mortality in hip fracture patients., Patients and Methods: A case matched comparison of mortality was conducted between C. difficile positive patients and C. difficile negative patients admitted with a hip fracture between 1st January 2003 and 30th September 2007. An interrupted time series analysis was performed to assess the effect of various infection control policies on the incidence of C. difficile infection., Results: The interrupted time series analysis showed that the only effective measure was changing antimicrobial prophylaxis to Co-amoxiclav in May 2007. This reduced the incidence of C. difficile from 7.1 to 1.5% (p<0.001). Six-month mortality in C. difficile positive patients was 71% 1 year before introduction of a diarrhoea treatment policy and 65% 1 year after (p=0.5) indicating treatment was ineffective. A matched cohort comparison over a 57-month period from January 2003 to September 2007 showed that the 6-month mortality was 67% in 170 C. difficile positive patients, 27% in 3247 C. difficile negative patients and 29% in the 170 C. difficile negative matched patients., Conclusion: This 38% excess mortality indicated that C. difficile increased mortality and did not simply colonise the sickest patients. Changing prophylaxis to Co-amoxiclav was the most effective measure. This reduced the incidence of C. difficile by 80% and thus reduced mortality by prevention rather than cure.

Objectives: Inflammatory bowel disease (IBD) is usually diagnosed as a result of symptoms but occasionally is found during investigation for other conditions. An earlier report from Nottingham had found a high prevalence of previously undetected "asymptomatic" IBD detected as a result of colorectal cancer screening, and the aim of this study was to reassess the prevalence, symptoms, and outcome in these patients., Methods: We investigated subjects found to be fecal occult blood (FOB) positive in a randomized trial of FOB screening for colorectal cancer. All FOB-positive subjects were investigated by colonoscopy or flexible sigmoidoscopy and barium enema. Subjects with IBD were referred back to their general practitioner for any further investigation and treatment., Results: Seventy-five thousand two hundred fifty-three subjects (aged 45-74) were sent FOB tests and 44,838 (60%) completed a series of tests on one or more occasions. Of 133,000 test series, 1.5% were positive. During investigation 53 cases of previously undetected IBD (52 of ulcerative colitis) were found; 52% (27/52) had proctosigmoiditis only, whereas 25% (13/52) had pancolitis. Only 17% (9/52) were completely asymptomatic, with a half or more reporting some rectal bleeding (54%) or diarrhea (50%). The overall prevalence of undetected ulcerative colitis was 69/10(5) (95% CI = 50-88/10(5)) in people offered screening and 116/10(5) (95% CI = 85-147/10(5)) in people accepting screening and was higher in men. Of 32 subjects followed up 2-12 yr after diagnosis, 91% (29) continued to have few or no symptoms, with only 12 currently receiving any treatment for their colitis., Conclusions: In comparison with detected disease, undetected ulcerative colitis is relatively common but does usually cause some symptoms. It generally appears to follow a benign course, but a significant proportion have extensive colitis and may therefore be at an increased risk of colorectal cancer.

Thirty-six encoded isolates of Escherichia coli. 32 of which were of serotype O157, were examined by pyrolysis mass spectrometry (PyMS). Thirty-one of the serotype O157 isolates possessed the flagellar antigen H7 and produced Verocytotoxin (VT), the other isolate serotyped as H45 and was non-toxigenic. Eighteen of the VT-producing E. coli (VTEC) isolates were from sporadic disease in residents of the Northern Region. Standard principal component (PC) and canonical variate (CV) analysis of the data distinguished only the four non-O157 isolates from the remainder which were indistinguishable by this approach. A similarity matrix based on differences between individual CV means distinguished a further ten isolates. The matrix correctly clustered 2 pairs of isolates from siblings and 4 isolates from an affected family. A further 5 clusters of 3 or more isolates and 6 pairs of isolates were defined. These groupings proved to be homogenous for toxin phenotype but occasionally entrained isolates of dissimilar phage type. However, in general, PyMS-derived clustering of apparently sporadic isolates accorded with geographical locations as determined by postcode. PyMS, which is a quick and high volume capacity phenotypic technique, may be a useful addition to existing methods in the investigation of the epidemiology of sporadic VTEC disease.

Inherited susceptibility to Type 1 (insulin-dependent) diabetes mellitus is partly determined by HLA genes. It has been suggested that protection from disease may be conferred by HLA-DQB1 genes which encode molecules with aspartate at position 57. We investigated the contributions of HLA-DRB1, DQA1 and DQB1 genes to protection from disease. Restriction fragment length polymorphism and sequence specific oligonucleotide analysis in 156 British Caucasian Type 1 diabetic and 116 control subjects showed protection from disease was associated with DR2, DRw6 and DR7 haplotypes. The most protective DQA1 allele was DQA1*0102 which occurred on both DR2 and DRw6 haplotypes. The DQB1 alleles DQB1*0303, DQB1*0602 and DQB1*0603 were associated with protection, as was DQB1*0604, which encodes an Asp-57 negative DQ beta molecule. Heterozygosity for both protective and predisposing HLA markers was reduced in diabetic compared with control subjects. We conclude that both DQA1 and DQB1 genes are implicated in HLA-associated protection from Type 1 diabetes in this British Caucasian population. The overall structure of the DQ heterodimer is critical and DQ beta-Asp 57 is of secondary importance in determining protection from disease. The effect of protective HLA types may predominate over that of predisposing markers.

Tumour necrosis factor gene polymorphism has been proposed as a determinant of Type 1 (insulin-dependent) diabetes mellitus. Tumour necrosis factor-beta gene polymorphisms were analysed in 40 North Indian Asian Type 1 diabetic patients and 63 control subjects. A 5.5 kilobase gene fragment was significantly increased among the patients (82.5% vs 52%, pc less than 0.01). A 10.5 kilobase fragment was significantly reduced among the patients (70% vs 90.5%, pc less than 0.02). The 5.5 kilobase fragment was associated with DR3, and was not significantly increased among DR3-positive patients compared with DR3-positive control subjects. The 5.5 kilobase/5.5 kilobase genotype was increased among the diabetic subjects (30% vs 9.5%, pc less than 0.03). The 10.5 kilobase/10.5 kilobase genotype was reduced among the diabetic subjects (17.5% vs 47.5%, pc less than 0.02). The 5.5 kilobase/10.5 kilobase genotype was not significantly associated with disease. These findings contrast with those in a white Caucasian population, suggesting that tumour necrosis factor-beta polymorphisms do not predispose to Type 1 diabetes directly, but are in linkage disequilibrium with disease susceptibility alleles at other MHC loci.

Transracial analysis provides a method of distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA class II alleles from those secondary to linkage disequilibrium. Blacks show DR-DQ relationships that are different from other races and are a useful group in which to investigate HLA-D region associations with IDDM. In this study, the frequencies of HLA-DQA1 and -DQB1 alleles in Afro-Caribbean IDDM and control subjects were compared. Alleles were identified with sequence-specific oligonucleotide probing. The DQA1 allele A3 was positively associated with IDDM (relative risk [RR] = 25.3, corrected P [Pc] less than 7.0 x 10(-6). The DQB1 alleles DQw2 and DQw8 were also positively associated (RR = 4.7, Pc less than 6.5 x 10(-3) and RR = 12.3, Pc = 3.4 x 10(-3), respectively). The A1.2 and DQw6 alleles were negatively associated (RR = 0.16, Pc less than 3.5 x 10(-3) and RR = 0.15, Pc = 2.4 x 10(-2), respectively). These findings were compared to data from other races. The positive associations with A3 and DQw2 are consistent with all racial groups investigated. The negative association with DQw6 is present in all racial groups in which it is a common allele. These findings suggest that DQ alleles, and hence DQ molecules, may directly affect predisposition to IDDM.

Type 1 (insulin-dependent) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQ alpha, DQ beta and DR beta chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQ beta restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7% vs 10.4%, respectively; p less than 10(-4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQ alpha-DQ beta patterns, only one of which was positively associated with diabetes. A DQ beta pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes.