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Extranodal non-Hodgkin's lymphoma (NHL) within the female genital tract is unusual, accounting for 1.5% of extranodal NHL, mostly in the ovaries. Primary NHLs of the uterus and cervix are rare, comprising only 0.54%–0.64% of all extranodal NHLs, most occurring in the cervix.1 Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) of the uterus is extremely rare, with only seven cases reported in the literature.2–8 We report a rare case of an extranodal marginal zone B cell lymphoma arising from the MALT tissue of the endometrium. A 77-year-old woman presented with utero-vaginal prolapse, urinary frequency and nocturia; she had no B symptoms. Examination revealed a cystocoele and a cervical prolapse. There was no palpable lymphadenopathy or hepatosplenomegally and she underwent vaginal hysterectomy and pelvic floor repair. The uterus and cervix measured 8.3×2.6×2.2 cm. The endometrium was 0.2 cm thick and the myometrium 1.6 cm thick; both appeared normal. Microscopically, the endometrium and superficial myometrium contained a nodular infiltrate of monotonous, small to medium-sized, lymphoid cells (figure 1A). The cells …

Objectives: To quantify the extent of the variation in hospital admission rates between general practices, and to investigate whether this variation can be explained by factors relating to the patient, the hospital, and the general practice. Design: Cross sectional analysis of routine data. Setting: Merton, Sutton, and Wandsworth Health Authority, which includes areas of inner and outer London. Subjects: 209 136 hospital admissions in 1995-6 in patients registered with 120 general practices in the study area. Main outcome measures: Hospital admission rates for general practices for overall, emergency, and elective admissions. Results: Crude admission rates for general practices displayed a twofold difference between the 10th and the 90th centile for all, emergency, and elective admissions. This difference was only minimally reduced by standardising for age and sex. Sociodemographic patient factors derived from census data accounted for 42% of the variation in overall admission rates; 45% in emergency admission rates; and 25% in elective admission rates. There was a strong positive correlation between factors related to deprivation and emergency, but not elective, admission rates, raising questions about equity of provision of health care. The percentage of each practice9s admissions to different local hospitals added significantly to the explanation of variation, while the general practice characteristics considered added very little. Conclusions: Hospital admission rates varied greatly between general practices; this was largely explained by differences in patient populations. The lack of significant factors related to general practice is of little help for the direct management of admission rates, although the effect of sociological rather than organisational practice variables should be explored further. Admission rates should routinely be standardised for differences in patient populations and hospitals used. Key messages There is substantial variation in hospital admission rates between general practices Patient factors were by far the most important in explaining this variation whereas general practice characteristics explained a negligible amount, providing little help to those with an interest in managing admissions Deprivation was more strongly related to emergency rather than to elective admission rates, raising issues around equity of healthcare provision Admission rates should be standardised for differences in patient populations and hospitals used to give fair and meaningful comparisons between general practices Improvements in the quality of routine health services data are essential to enable health authorities and primary care groups to interpret information correctly

Hepatic artery resistance index has been measured by ultrasonography Doppler and has been found to predict rapid deterioration and death in children with biliary atresia. Clinical, biochemical, ultrasonographic, and outcome data were collected prospectively and retrieved on 32 patients with resistance index of > or = 1.0 (group A). These were compared with the same data for 32 age- and sex-matched patients with biliary atresia and a resistance index of ≤ 1.0 (group B). Group A was found to have significantly worse liver function tests than group B. In group A, all patients died (n = 11) or underwent transplantation (n = 21; of whom 4 died) compared with only 2 patients who died in group B and 4 patients who underwent transplantation without fatality. Survival at 2 years was 52% in group A v 94% in group B. It is suggested that regular ultrasonography Doppler examination in patients with biliary atresia can detect a group with a resistance index of > 1.0 who have a very high risk of early mortality. Such patients require early evaluation and listing for transplantation. Those listed for liver transplantation on other grounds require ultrasonography examinations every 2 to 3 months with immediate upgrading of the priority of those patients found to have a resistance index of ≤ or = 1.0. (Liver Transpl Surg 1997 Nov;3(6):604-10)

Background Pelvic organ prolapse is common, with some degree of prolapse seen in up to 50% of parous women in a clinic setting, although many are asymptomatic. The use of pessaries (a passive mechanical device designed to support the vagina) to treat prolapse is very common, and up to 77% of clinicians use pessaries for the first line management of prolapse. A number of symptoms may be associated with prolapse and treatments include surgery, pessaries and conservative therapies. A variety of pessaries are described which aim to alleviate the symptoms of prolapse and avert or delay the need for surgery. Objectives To determine the effectiveness of pessaries (mechanical devices) for pelvic organ prolapse. Search methods We searched the Cochrane Incontinence Group Specialised Register of trials (searched 13 March 2012), which includes searches of CENTRAL, MEDLINE, PREMEDLINE and handsearching of conference proceedings, and handsearched the abstracts of two relevant conferences held in 2011. We also searched the reference lists of relevant articles. Selection criteria Randomised and quasi-randomised controlled trials which included a pessary for pelvic organ prolapse in one arm of the study. Data collection and analysis Abstracts were assessed independently by two authors with arbitration from a third if necessary. Data extraction was completed independently for included studies by two review authors. Main results To date there is only one published randomised controlled trial assessing the use of pessaries in the treatment of pelvic organ prolapse. Authors' conclusions The review authors identified one randomised controlled trial comparing ring and Gellhorn pessaries. The results of the trial showed that both pessaries were effective for the approximately 60% of women who completed the study with no significant differences identified between the two types of pessary. However, methodological flaws were noted in the trial, as elaborated under risk of bias assessment. There is no consensus on the use of different types of device, the indications nor the pattern of replacement and follow-up care. There is an urgent need for randomised studies to address the use of pessaries in comparison with no treatment, surgery and conservative measures.

Background Before being able to plan for end of life care, a doctor must first recognise that a patient is dying. A recent review has highlighted that doctors are not very good at this (Neuberger, 2013). Aim We set out to develop a “test” to assess how accurate doctors are at recognising dying. The test will consist of case studies, or “vignettes”, based on real palliative care patients. Methods In order to create the vignettes for the test, we undertook a prospective observational study of patients at two sites (a hospice and a hospital palliative care team). Any inpatient, over 18 years old, English speaking, and who was identified by the palliative care team as likely to die within the next two weeks was eligible. The clinical course of each patient was observed and was used to create a vignette, which formed the basis of the prognostic test. Results 50 participants were recruited and 20 were used to devise a prognostic test. For each vignette, clinicians were asked to assess the likelihood of death in the next 72 hours (scale 0% to 100%) based on the information presented. Illustrative examples of the test questions will be presented at the conference. Conclusions We have developed a standardised test to assess clinicians’ abilities to accurately diagnose imminent death. This test may be used to identify doctors who are most accurate at recognising dying. This may lead to an improved understanding of how this clinical skill is acquired and how it can be taught to less expert clinicians. Reference Neuberger J. More care, less pathway: a review of the Liverpool Care Pathway; 2013. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/212450/Liverpool_Care_Pathway.pdf

Background: There may be an increased risk of colorectal cancer after cholecystectomy, but the literature is not consistent. It is also possible that any risk might be associated with gallstones rather than cholecystectomy. Methods: In a prospective necropsy study of 8563 cases, all 219 cases of a previous cholecystectomy were pair-matched to subjects with gallstones and to subjects with a normal gallbladder. In a second study all 192 cases of colorectal cancers were pair-matched to cancer-free subjects. Results: The odds ratio (OR) for developing colorectal cancer after cholecystectomy compared with a normal gallbladder was 1.0 (95% confidence interval, 0.30-3.34) and with unoperated gallstones was 0.88 (0.27-2.76). Conclusions: This study fails to support an association between cholecystectomy or gallstones and colorectal cancer. For those cases of colorectal cancer versus controls, the OR for previous cholecystectomy was 0.70 (0.23-2.04) and for gallstone disease was 0.93 (0.58-1.48).

The objective of this study was to create a valid, reliable, and responsive sexual function measure in women with pelvic floor disorders (PFDs) for both sexually active (SA) and inactive (NSA) women. Expert review identified concept gaps and generated items evaluated with cognitive interviews. Women underwent Pelvic Organ Prolapse Quantification (POPQ) exams and completed the Incontinence Severity Index (ISI), a prolapse question from the Epidemiology of Prolapse and Incontinence Questionnaire (ISI scores), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Female Sexual Function Index (FSFI). Principle components and orthogonal varimax rotation and principle factor analysis with oblique rotation identified item grouping. Cronbach’s alpha measured internal consistency. Factor correlations evaluated criterion validation. Change scores compared to change scores in other measures evaluated responsiveness among women who underwent surgery. A total of 589 women gave baseline data, 200 returned surveys after treatment, and 147 provided test-retest data. For SA women, 3 subscales each in 2 domains (21 items) and for NSA women 2 subscales in each of 2 domains (12 items) emerged with robust psychometric properties. Cronbach’s alpha ranged from .63 to .91. For SA women, correlations were in the anticipated direction with PFDI-20, ISI, and FSFI scores, POPQ, and EPIQ question #35 (all p

The objective of the study was to identify reasons why women declined participation in a pilot randomised controlled trial (RCT) comparing tension-free vaginal tape (TVT) under general anaesthetic (GA) with single incision sling (SIS) under local anaesthetic (LA). These data would inform the design of a larger trial to improve patient recruitment.This was a qualitative interview study on women eligible to have a TVT for stress urinary incontinence in a tertiary referral hospital in the UK. Women were counselled in a standardised manner. They were informed that the short-term success rates were similar for both operations. Women who declined to take part in the RCT were interviewed using a topic guide. Themes and sub-themes on non-participation were identified by two independent observers using a constant comparison method.Twenty-three non-participants of the RCT were interviewed. Common themes for non-participation were a preference for TVT and request for GA. Sub-themes showed that the TVT was preferred due to its perceived better efficacy as well as a minimal benefit from a SIS and also an unwillingness to take unknown risks. GA was favoured due to fear of local awareness, past negative experiences and embarrassment. Additional tests and follow-up visits were not cited as a reason for non-participation.The study found that non-participants are not research averse in general but they had strong preferences about specific aspects of treatment. Risk propensity and personality may also influence this behaviour. The study also demonstrates how a qualitative pilot study may improve trial design.

OBJECTIVE: To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls. DESIGN: Cohort study SETTING: 20 London universities and further education colleges. PARTICIPANTS: 2185 sexually active female students, mean age 21 years (range 16-27), 38% from ethnic minorities, who took part in the POPI (prevention of pelvic infection) chlamydia screening trial in 2004-08 and who provided duplicate, self taken vaginal swabs and completed questionnaires at baseline. At follow-up, a median of 16 months later, 821 women (38%) returned repeat vaginal swabs by post. In 2009-10, stored samples were tested for HPV. RESULTS: Samples from 404/2185 (18.5% (95% CI 16.9% to 20.2%)) of the cohort were positive for carcinogenic HPV at baseline, including 15.0% (327) positive for non-vaccine carcinogenic genotypes. Reporting two or more sexual partners in the previous year and concurrent Chlamydia trachomatis or bacterial vaginosis were independent risk factors for prevalent vaginal HPV infection. Infection with one or more new HPV types was found in 17.7% (145/821) of follow-up samples, giving an estimated annual incidence of carcinogenic HPV infection of 12.9% (95% CI 11.0% to 15.0%). Incident infection was more common in women reporting two or more partners in the previous year, aged

Little is known about where sexually active female students access healthcare.Using data from the Prevention of Pelvic Infection (POPI) cohort, the authors aimed to: Describe where sexually active female students aged ≤ 27 years reported accessing healthcare. Investigate the association between numbers of sexual partners during 12 months of follow-up and healthcare usage, health-related quality of life (EQ-5D) and demographic and behavioural characteristics.Participants provided vaginal swabs and completed questionnaires on sexual health and quality of life at baseline and at a 12-month follow-up. The follow-up questionnaire also asked about healthcare attendances during the previous 12 months. Mann-Whitney tests were used to relate healthcare seeking behaviour and other characteristics to reported numbers of partners during follow-up.Of 1865 women included in the analysis, 79% paid at least one visit to their general practice during follow-up, 23% attended an accident and emergency/walk-in clinic, 21% a family planning clinic and 14% a genitourinary medicine clinic. As the number of sexual partners increased (0-1, 2-3, 4+), women were more likely to have visited a genitourinary medicine clinic (10%, 16%, 30%, p0.001) or accident and emergency/walk-in clinic (21%, 26%, 29%, p0.002). Women with more sexual partners were also more likely to smoke, use condoms, be aged16 years at sexual debut, have bacterial vaginosis, chlamydia or gonorrhoea at baseline and to have lower EQ5-D scores.This is the first UK study of healthcare attendance in multiethnic female students recruited outside healthcare settings. The high attendance in general practice may represent a valuable opportunity for screening for sexually transmitted infections.

BACKGROUND The charity 'Health Partnership Nepal' is committed to both improving global health care and providing medical training links between Nepal and the UK. This paper analyses data gathered at rural health camps. AIM To describe the demographics, diagnoses and treatments offered to people attending three rural health camps in Nepal during 2009. Design Cross-sectional study. Setting Three free health care camps established within the Nuwakot district of Nepal during April-May 2009. Camps were staffed by doctors including GPs, nurses and medical students from London and Kathmandu. METHODS Attendees had treatment sheets completed which recorded their demographics, diagnoses and dispensed medications. RESULTS The mean age of the 1903 consecutive patients attending was 42.8 years (range one month to 98 years) of whom 68.6% were female and 13.7% were children. The majority, 82.3%, were agricultural workers. For adults (n = 1574), the most frequent complaints were stomach pain 20.1%, musculoskeletal pain 19.3% and visual acuity problems 6.1%. Stomach pain was significantly more common in women than men [21.2% (236/1064) versus 14.5% (65/449) P < 0.01]. For children (n = 249), the most common diagnoses were helminthiasis 10.4%, conjunctivitis 7.6% and upper respiratory tract infection 7.2%. Overall, opthalmological, gastroenterological and rheumatological diagnoses were significantly more common in Nepalese than UK general practice patients. Of 1109 recorded prescriptions, the most common were multivitamins 23%, oral analgesics 15% and oral antibiotics 14%. CONCLUSIONS There is a considerable unmet disease burden within rural districts of Nepal particularly for stomach pain, musculoskeletal pain and visual acuity problems. When planning similar rurally based health camps, we recommend recruiting GPs and ophthalmologists.

Objectives To investigate if lifestyle in spina bifida at age 40±3 years, relates to neurological deficit in infancy or cerebrospinal fluid shunt history. Design Prospective cohort study with 100% ascertainment. Setting Community. Participants 117 consecutive cases of open spina bifida whose backs were closed non-selectively at birth. In 2007, all 46 (39%) survivors and/or carers were surveyed by postal questionnaires and telephone interviews. Results Of the 38 children with absent sensation only below the knee (sensory level below L3), 23 (61%) survived of whom 14 (61%) were community walkers and only 5 (22%) needed daily care. But in 42 babies with absent sensation up to the umbilicus (sensory level above T11) only seven (17%) survived, none could walk and five (71%) needed daily care. Survivors with no shunt revisions were more likely to walk, live independently and drive a car. Conclusion Mobility and the need for care at 40 can be predicted from the neurological deficit.

RATIONALE: Many smokers experience a decline in cortisol to sub-normal levels during the first days of smoking cessation. A greater decline in cortisol is associated with more intense cigarette withdrawal symptoms, urge to smoke and relapse to smoking. Findings from an uncontrolled study suggest that glucocorticoids could ameliorate cigarette withdrawal. OBJECTIVES: We investigated whether taking oral hydrocortisone would reduce withdrawal symptoms and the desire to smoke on the first day of temporary smoking abstinence compared with placebo. METHODS: Using a double-blind within-subject randomised crossover design, 48 smokers took a single dose of 40 mg hydrocortisone, 20 mg hydrocortisone or placebo following overnight smoking abstinence. Abstinence was maintained through the afternoon, and withdrawal symptoms and the desire to smoke were rated across the morning. Salivary cortisol was assessed in the afternoon prior to abstinence (baseline) and while abstinent after each treatment. RESULTS: There was a significant dose-response relation between dose of hydrocortisone and reduction in depression and anxiety ratings while abstinent, but there were no other statistically significant associations with dose. Overall, the decline in cortisol following smoking cessation (placebo only) was not significant. Cortisol level on the afternoon of smoking abstinence was not significantly associated with symptom ratings. CONCLUSIONS: Supplements of hydrocortisone do not reduce the desire to smoke but may ameliorate withdrawal-related depression and anxiety, although the clinical benefit is slight.

We have previously documented the on-going work in the EUFORIA project to parallelise and optimise European fusion simulation codes. This involves working with a wide range of codes to try and address any performance and scaling issues that these codes have. However, as no two simulation codes are exactly the same, it is very hard to apply exactly the same approach to optimising a disparate range of codes. Indeed, the codes investigated range in terms of performance and ability from well-optimised, highly parallelised codes, to serial or poorly performing codes. After analysing, optimising, and parallelising a range of codes it is, actually, possible to discern a number of distinct optimisation techniques or approaches/strategies that can be used to improve the performance or scaling of a parallel simulation code. This paper outlines the distinct approaches that we have identified, highlighting their benefits and drawbacks, giving an overview of the type of work that is often attempted for fusion simulation code optimisation. performing codes. After analysing, optimising, parallelising, and scaling a range of codes it is, actually, possible to discern a number of distinctoptimisation techniques or approaches/strategies that can be used to improve the performance or scaling of a parallel simulation code. This paper outlines the distinct approaches that we have identified, highlighting their benefits and drawbacks, giving an overview of the type of work that is often attempted for fusion simulation code optimisation.

Background. The role of Mycoplasma genitalium in pelvic inflammatory disease is unclear. We conducted a cohort study to determine the prevalence and predictors of M. genitalium infection in female students, to explore its role in pelvic inflammatory disease and to estimate its annual incidence and persistence rate. Methods. Two thousand three hundred seventy-eight multiethnic, sexually active female students (mean age, 21 years) provided duplicate self-taken vaginal samples for a chlamydia screening trial. From this population, 2246 (94%) were followed up after 12 months and assessed for incidence of clinical pelvic inflammatory disease. In addition, 900 women (38%) returned follow-up samples via the postal service 11-32 months after recruitment. Stored samples were tested for M. genitalium. Results. The prevalence of M. genitalium at baseline was 3.3% (78 of 2378 women; 95% confidence interval [CI], 2.6%-4.1%). Infection was more common in women reporting ≥2 sexual partners in the previous year, those with bacterial vaginosis, women aged

Assessment of the 2-year outcome of anterior Prolift™ for women with recurrent anterior vaginal wall prolapse. This is a prospective study which was conducted in a tertiary unit in the North West of England and comprised 36 consecutive women with recurrent anterior vaginal wall prolapse. Women were assessed preoperatively and postoperatively at 6 months and 2 years. Women completed the Prolapse Quality of Life Questionnaire (P-QOL), Prolapse and Incontinence Sexual Function Questionnaire-Short Form (PISQ-12), and postoperatively, the Global Impression of Improvement Questionnaire. Women were examined using the Pelvic Organ Prolapse Quantification System (POP-Q). Anatomical success was defined as stage ≤1 prolapse in the anterior compartment. Main outcome measures Postoperative POP-Q stage, quality of life domains and mesh exposure rate. Preoperatively all but two women had stage 2 or greater anterior vaginal wall prolapse. At a mean follow-up of 24.6 months, 19 women (53%) had stage ≤1 anterior wall prolapse. Fifteen women had stage 2 anterior wall prolapse and two women had stage 3 prolapse. Twenty-nine women felt improvement in their prolapse symptoms. 16 women were sexually active preoperatively, of whom seven reported worsening dyspareunia. There was poor correlation between anatomical and functional outcomes. Seven women had mesh exposure. Five needed revision in theatre. Anterior Prolift™ for recurrent anterior vaginal wall prolapse has 53% anatomical success rate in the medium term, with mesh exposure rate of 19%. Majority of patients felt overall improvement in their symptoms, but this did not correlate with the anatomical outcome.

L’article explore les processus d’expulsion, d’exclusion et d’exil, en s’intéressant à l’expérience des civils et des non-combattants dans les années trente et quarante. Plusieurs questions fondamentales sont examinées : quels sont les facteurs qui ont transformé des gens plutôt ordinaires en « réfugiés », c’est-à-dire en personnes extraordinaires ? Comment ont-ils appréhendé ce passage d’un statut « d’homme ordinaire » à celui de « réfugié » ? Forment-ils une population minoritaire, dont la situation est exceptionnelle ? Ou peut-on considérer leurs expériences comme emblématiques voire typiques de leur époque ? This article discusses the processes of expulsion, exclusion and exile, concentrating on the experience of civilians and non-combatants in the 1930s and 1940s. Several important questions are addressed: what are the factors that transformed ordinary people into the extraordinary ‘refugees’? How did they understand this shift from ‘ordinary person’ to ‘refugee’? Were they a minority, an exceptional part of the population? Or can their experiences be considered as emblematic, even typical of their era? El artículo explora los procesos de expulsión, exclusión y exilio, interesándose por la experiencia de los civiles et de los no combatientes durante los años treinta y cuarenta. Varias preguntas fundamentales son examinadas: ¿cuáles fueron los factores que convirtieron a personas más bien ordinarias en “refugiados”, es decir en personas extraordinarias? ¿Cómo sintieron este paso de un estatuto “de hombre ordinario” al de “refugiado”? ¿Forman una población minoritaria, cuya situación es excepcional? ¿Acaso puede considerarse sus experiencias como emblemáticas e incluso típicas de su época?

BackgroundA growing number of European studies, particularly from Nordic countries, suggest an increased frequency of autism in children of immigrant parents. In contrast, North American studies tend to conclude that neither maternal ethnicity nor immigrant status are related to the rate of autism-spectrum disorders.AimsTo examine the hypotheses that maternal ethnicity and/or immigration are linked to the rate of childhood autism-spectrum disorders.MethodRetrospective case-note analysis of all 428 children diagnosed with autism-spectrum disorders presenting to the child development services in two centres during a 6-year period.ResultsMothers born outside Europe had a significantly higher risk of having a child with an autism-spectrum disorder compared with those born in the UK, with the highest risk observed for the Caribbean group (relative risks (RRs) in the two centres: RR = 10.01, 95% CI 5.53–18.1 and RR = 8.89, 95% CI 5.08–15.5). Mothers of Black ethnicity had a significantly higher risk compared with White mothers (RR = 8.28, 95% CI 5.41–12.7 and RR = 3.84, 95% CI 2.93–5.02). Analysis of ethnicity and immigration factors together suggests the increased risk is predominately related to immigration.ConclusionsMaternal immigration is associated with substantial increased risk of autism-spectrum disorders with differential risk according to different region of birth and possibly ethnicity.

The aim of our study was to investigate survival and causes of death in a complete cohort of open spina bifida at the mean age of 40 years.We conducted a community-based, prospective study of 117 consecutive infants (50 males, 67 females) with open spina bifida whose backs were closed non-selectively within 48 hours of birth between 1963 and 1971 at Addenbrooke's Hospital, Cambridge, UK. Of those who survived to age 1 year, 89% (82 out of 92) had a cerebrospinal fluid shunt. In 2007, all survivors were surveyed by postal questionnaire backed up by telephone interview. Details of deaths were obtained from the Office for National Statistics, medical records, and autopsy reports, and Kaplan-Meier survival curves were constructed.One in three of the cohort (40/117) died before the age of 5 years. A further 26% (31/117) died during the next 35 years, over 10 times the national average. Half the deaths (16/31) after the age of 5 were sudden and unexpected. All occurred in the community and were followed by a coroner's autopsy. The most frequent causes of these unexpected deaths were epilepsy, pulmonary embolus, acute hydrocephalus, and acute renal sepsis. The prognosis for survival was strikingly poor in those with the most extensive neurological deficit. Only 17% (7/42) of those born with a high sensory level (above T11) survived to the mean age of 40 years, compared with 61% (23/38) of those with a low sensory level (below L3; p=0.001).Doctors and care planners need to be aware that, contrary to previous suggestions, there is continuing high mortality throughout adult life in individuals with open spina bifida, and many deaths are unexpected.

UK National Cancer Registration data indicates that some35, 000 people each year are diagnosed with colorectal cancer (cancer of the large bowel and rectum) and 16, 000 die from the disease. The Colon Cancer Genetics Group (CCGG) at the University of Edinburgh investigates the relationship between genetic markers and colorectal cancer by using a significant part (560, 000 markers, 1000 cases, 1000 controls) of the biggest genotypic data set for large bowel cancer. However, the analysis is virtually intractable for a PC-based researcher (theoretical runtime of 400 days; 3.3TB of memory and hard disk space). CCGG collaborated with EPCC, the supercomputing centre of the University of Edinburgh, to optimise and parallelise the analysis code. We achieved a runtime of approximately 5 hours on 512 processor cores on HECToR, the national supercomputer of the UK. The use of EPCC’s skills and HPC resources has enabled CCGG to explore new territory for genetic marker analysis in colorectal cancer.

Background Chronic kidney disease (CKD) is a relatively newly recognised but common long-term condition affecting 5 to 10% of the population. Effective management of CKD, with emphasis on strict blood pressure (BP) control, reduces cardiovascular risk and slows the progression of CKD. There is currently an unprecedented rise in referral to specialist renal services, which are often located in tertiary centres, inconvenient for patients, and wasteful of resources. National and international CKD guidelines include quality targets for primary care. However, there have been no rigorous evaluations of strategies to implement these guidelines. This study aims to test whether quality improvement interventions improve primary care management of elevated BP in CKD, reduce cardiovascular risk, and slow renal disease progression Design Cluster randomised controlled trial (CRT) Methods This three-armed CRT compares two well-established quality improvement interventions with usual practice. The two interventions comprise: provision of clinical practice guidelines with prompts and audit-based education. The study population will be all individuals with CKD from general practices in eight localities across England. Randomisation will take place at the level of the general practices. The intended sample (three arms of 25 practices) powers the study to detect a 3 mmHg difference in systolic BP between the different quality improvement interventions. An additional 10 practices per arm will receive a questionnaire to measure any change in confidence in managing CKD. Follow up will take place over two years. Outcomes will be measured using anonymised routinely collected data extracted from practice computer systems. Our primary outcome measure will be reduction of systolic BP in people with CKD and hypertension at two years. Secondary outcomes will include biomedical outcomes and markers of quality, including practitioner confidence in managing CKD. A small group of practices (n = 4) will take part in an in-depth process evaluation. We will use time series data to examine the natural history of CKD in the community. Finally, we will conduct an economic evaluation based on a comparison of the cost effectiveness of each intervention. Clinical Trials Registration ISRCTN56023731. ClinicalTrials.gov identifier.

Objective: This article describes the three-stage development of the SCOFF, a screening tool for eating disorders. Method: Study 1 details questionnaire development and testing on cases and controls. Study 2 examines reliability of verbal versus written administration in a student population. Study 3 validates the test as a screening tool in primary care. Results: The SCOFF demonstrates good validity compared with DSM-IV diagnosis on clinical interview. In the primary care setting it had a sensitivity of 84.6% and a specificity of 89.6%, detecting all true cases of anorexia nervosa and bulimia nervosa and seven of nine cases of EDNOS. Reliability between written and verbal versions of the SCOFF was high, with a kappa statistic of 0.82. Discussion: The SCOFF, which has been adapted for use in diverse languages, appears highly effective as a screening instrument and has been widely adopted to raise the index of suspicion of an eating disorder. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010

We have been able to solve a reservoir simulation problem which was previously thought of as intractable: We simulated multiphase displacement, including viscous, capillary, and gravitational forces, for highly resolved and geologically realistic models of naturally fractured reservoirs (NFR) at the sector, i.e., kilometre, scale with very reasonable runtime. This has been possible because we used massive parallelisation and hierarchical solvers in conjunction with a new discrete fracture and matrix modelling (DFM) technique that is based on mixed-dimensional unstructured hybrid-element discretisations. High-resolution DFM simulations are important to resolve the non-linear coupling of small scale capillary - viscous and large scale gravitational - viscous processes adequately for sector scale NFR. Cross-scale process coupling in NFR controls oil recovery and NFR often exhibit power-law fracture length distributions, i.e. they do not possess an REV, and highly permeable fractures can extend over the full hydrocarbon column height. As a consequence, emergent displacement patterns have been observed which are difficult to quantify using traditional means of upscaling. However, such patterns could now be used as benchmarks to reach a better concensus on the correctness of promising new upscaling techniques. The parallel DFM technologies presented here allow us to obtain these results much more efficiently and hence explore the parameter space in greater detail. We observed a linear scaling behaviour for up to 64 processes and a significant decrease in runtime when applying our parallel DFM approach to three highly refined NFR simulations. These contain thousands of fractures, up to 5 million elements, and have local grid-refinements below 1 m for model dimensions between 1 and 10 kilometres. We achieved this excellent speedup because we reduced inter-processor communication by minimising the overlap between individual domains and decreased idle time of individual processors by distributing the number of unknowns equally among the processors. Introduction Production from naturally fractured reservoirs (NFR), which contain a major part of the world's remaining oil reserves, is challenging. NFR often suffer from a low final recovery that leaves between 80 to 95% of the oil underground which is retained in the low-permeability rock matrix (Kazemi and Gilman, 1993). Traditionally, production from NFR is simulated with dual-porosity models (Warren and Root, 1963). They represent the reservoir by a flowing domain of high permeability, the network of connected fractures, which is coupled to a stagnant domain, the low-permeability rock matrix. Exchange of oil, gas and water between the two domains is modelled by transfer functions. The rate of fluid transfer between fracture and matrix depends on the pressure gradient between the two domains and a shape factor, which represents the geometry of the rock matrix. The advantage of dual-porosity models is that they can be readily used in standard industry finite-difference or streamline reservoir simulators (Huang et al., 2004).

The aim of this study is to provide long-term outcome data, at least 10 years, following laparoscopic colposuspension. The study includes a control group who underwent open colposuspension. A consecutive series of 139 women who had undergone laparoscopic colposuspension were reviewed and compared to 52 women who had an open colposuspension in the same unit. Subjects were contacted by telephone, at least 10 years post-operatively, at which time a structured interview was performed which included the short-form Bristol Female Lower Urinary Tract Symptom questionnaire. There was deterioration in subjective cure rates from 71% and 67% at 6 months to 52% and 36% at 10 years for the laparoscopic and open procedures, respectively. This study provides evidence that laparoscopic colposuspension is probably as durable as open colposuspension. However, cure rates for both procedures appear to deteriorate over time, emphasising the importance of long-term follow-up.

Background Health literacy (HL) has been recognized as an important public health issue in other developed countries such as the US. There is currently no HL screening tool valid for use in the UK. This study aimed to validate a US-developed HL screening tool (the Rapid Estimate for Adult Literacy in Medicine; REALM) for use in the UK against the UK's general literacy screening tool (the Basic Skills Agency Initial Assessment Test, BSAIT). Methods A cross-sectional survey involving 300 adult patients admitted to hospital for investigation of coronary heart disease were given the REALM and BSAIT tools to complete as well as specific questions considered likely to predict HL. These questions relate to the difficulty in understanding medical information, medical forms or instructions on tablets, frequency of reading books and whether the participant's job involves reading. Results The REALM was significantly correlated with the BSAIT (r = 0.70; P < 0.001), and significantly related to seven of the eight questions likely to be predictive of HL. Conclusions This study has shown that the REALM has face, criterion and construct validity for use as an HL screening tool in the UK, in research and in everyday clinical practice. Further studies are needed to assess the prevalence of low HL in a wider population and to explore the links that may exist between low HL and poor health in the UK.

Aims and objectives. The aim was to develop a questionnaire for use by practitioners working in stroke care to measure self-efficacy judgements in specific domains of functioning relevant to individuals following stroke. Background. The prevalence of stroke is set to rise across the developed world especially amongst the elderly population. Recovery and adjustment in the longer term can be affected by many different factors. Current objective measures of functional performance used in many stroke programmes may not fully explain the extent of personal levels of confidence that could ultimately influence outcome. Methods. Three separate studies were conducted to develop the Stroke Self-Efficacy Questionnaire. A total of 112 stroke survivors, between 2 and 24 weeks, poststroke participated in the study. Development of the scale was undertaken between 2004 and 2006. Results. The final 13-item Stroke Self-Efficacy Questionnaire was found to have good face validity and feasibility to use in the recovery period following stroke. Cronbach Alpha was 0·90 suggesting good internal consistency, and criterion validity was high compared with the Falls Efficacy Scale, r = 0·803, p

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

PURPOSE OF REVIEW: The aim of this review is to present a summary of recently published research comparing laparoscopic and open colposuspension. It also examines the place of colposuspension in light of the continuing development other minimally invasive procedures for stress urinary incontinence. RECENT FINDINGS: The results of two large multicentre randomised controlled trials were published in 2006 comparing open and laparoscopic colposuspension. Carey et al. randomised 200 women to open or laparoscopic colposuspension. The primary outcome objective was cure 6 months postoperatively. Cure was defined as the absence of urodynamic stress incontinence. Patients' subjective outcomes were assessed 3-5 years postoperatively. Kitchener et al. reported a randomised controlled trial in which 291 women were recruited. The primary end point of the study was objective cure at 2 years. This was defined as

Background Serological case-control studies suggest that certain chlamydia-related bacteria (Chlamydiales) that cause cows to miscarry might do the same in human beings. Included in the order Chlamydiales are Waddlia chondrophila, Chlamydophila abortus , and Chlamydia trachomatis . We aimed to investigate the prevalence of Chlamydiales in pregnant women, and possible associations with miscarriage or preterm birth. Methods We tested stored urine samples from a carefully characterised cohort of 847 pregnant women recruited at mean 49·3 (SD 10·1) days' gestation from 37 general practices in London, UK. Previous repeat testing of samples positive for Mycoplasma genitalium confirmed bacterial DNA integrity after storage. W chondrophila and pan-Chlamydiales specific real-time PCRs targeting the 16s rRNA gene were used to test samples. Samples positive on either of the two PCRs were subjected to DNA sequencing and Chlamydia trachomatis PCR. Outcomes were compared between infected and uninfected women with Fisher's exact test. Ethics review was conducted by Wandsworth, Croydon, and Riverside Research Ethics Committees. Findings The overall prevalence of Chlamydiales was 4·3% (36/847, 95% CI 3·0–5·8). Prevalence of W chondrophila was 0·6% (5/847, 0·2–1·4), Chlamydia trachomatis 1·7% (14/847, 0·9–2·8), and other Chlamydiales species 2·0% (17/847, 1·2–3·2). Infection with Chlamydia trachomatis (but not with other Chlamydiales or W chondrophila ) was more common in women younger than 25 years, of black ethnicity, or with bacterial vaginosis. Follow-up was 99·9% (846/847) at 16 weeks' gestation and 89·6% (759/847) at term. No infection was significantly associated with miscarriage (prevalence 10%, 84/827) or spontaneous preterm birth before 37 weeks' (4%, 23/628) but numbers were small. One of three (33%) followed-up women infected with W chondrophila had a preterm birth compared with 22 (4%) of 625 uninfected women (p=0·11). Sequencing of 25 samples that were positive on W chondrophila or pan-Chlamydiales PCR revealed seven samples (28%) positive for Chlamydiales bacterium sequences that have been associated with respiratory tract infections in children. Interpretation 4% of newly pregnant women tested positive for Chlamydiales, including species known to be pathogenic in mothers and neonates. Higher rates might have been found in vaginal samples and the study lacked power to test associations. Although W chondrophila might be associated with preterm birth, the prevalence was very low in this urban, community-based sample, suggesting that screening is unlikely to be cost-effective in such a population. Funding Medical Research Council.

OBJECTIVE Oral clindamycin reduced late miscarriage and preterm birth in asymptomatic women with bacterial vaginosis or intermediate flora. We investigated whether clindamycin reduced the incidence of histologic chorioamnionitis as a mechanism for these beneficial effects. METHODS This was a subanalysis of 126 participants from a larger randomized controlled trial. We compared the incidence of histologic chorioamnionitis between the clindamycin and placebo groups. Histologic chorioamnionitis was diagnosed by the presence of polymorphonuclear leukocytes, separately in the amnion and chorion, decidua, fetal surface of the placenta, the walls of fetal chorionic vessels, umbilical cord, or in the subchorionic fibrin layer. Microbiologic cultures were done on swabs from the space between the chorion and amnion layers. RESULTS Histopathologic results were available for 122 placentas, 62 (51%) and 60 (49%) in the clindamycin and placebo groups, respectively. There were no significant differences in inflammation between the groups in the decidua (41% compared with 43%), membranes (25% compared with 41%), fetal vessels (16% compared with 14%), or subchorionic fibrin (32% compared with 34%). Adjusting for gestational age, ethnic origin, or history of miscarriage did not alter the results. There were no significant differences in the outcomes of pregnancy between women with and without inflammation, either before or after adjustment for treatment group. CONCLUSION Although oral clindamycin reduced late miscarriage and preterm birth in women with abnormal vaginal flora, this effect is unlikely to be mediated through a reduction in the incidence of histologic chorioamnionitis. The relatively small size of the groups, however, does not allow us to rule out a real effect, especially given the lower rate of membrane inflammation observed in the clindamycin group. LEVEL OF EVIDENCE I.

A 42-year-old woman underwent total abdominal hysterectomy for menorrhagia. Her left ovary was also removed, as it appeared suspicious with nodules. During the operation, the left ureter was found ...

Aim: To determine guideline-related pharmaceutical care issues for the prevention of coronary heart disease in hospitalised patients admitted for myocardial infarction (MI). Methods: Consecutive patients admitted with a diagnosis of Q-wave MI to two large teaching hospitals were studied. Relevant patient medical and drug histories, co-morbidities and total cholesterol concentrations were recorded. Primary or secondary prevention treatment prior to admission was assessed using a data collection tool of 16 criteria developed from the Scottish Intercollegiate Guidelines Network (SIGN) guidelines. Main outcome measures: Frequency of adherence to defined clinical guideline criteria. Results: There were 167 patients reviewed (mean age 65 years, 111 males), representing possible candidates for primary prevention (n = 98) or secondary prevention (n = 69) based on absence or presence of past history of coronary heart disease (CHD), respectively. Possible primary prevention candidates: eight guideline-based criteria were developed from the SIGN guideline. There were 85 (87%) patients with a total cholesterol concentration available on admission of whom 56 (66%) had a predicted CHID risk greater than or equal to 15% and 10 (12%) had CHD risk greater than or equal to 30%. Of those with CHD risk greater than or equal to 15% 6 (11%) had been receiving an anti-platelet agent and of those with CHID risk greater than or equal to 30% only 1 (10%) was recorded as taking a statin. Of known hypertensives with CHD risk greater than or equal to 15%, 21% (5/24) were not recorded as having received treatment. Secondary prevention candidates: a further eight guideline-based criteria were developed from the SIGN guidelines. There were 42/65 (65%) candidates for aspirin documented as receiving it. There were 22/4.7 (47%) of those who had a total cholesterol greater than or equal to 5 mmol/l and/or known history of hypercholesterolaemia receiving a statin (representing 76% of the known hypercholesterolaemic patients identified in the community). Of statin-treated patients with a cholesterol measured on admission, 44% (7/16) had cholesterol remaining greater than or equal to 5 mmol/l. beta-blocker use was 27/62 (44%) and ACE inhibitors use was 11/31 (36%) of those eligible. Sublingual GTN was recorded in 36/69 (52%). Conclusion: The study has identified opportunities for improved pharmaceutical care in primary and secondary CHID prevention among those destined to suffer an MI. Candidates for secondary prevention are potentially identifiable from community pharmacy patient medication records from which the contribution of pharmacists in primary care might be targeted. The findings were obtained during a period of evolution of the evidence-base and so they establish a baseline for future work.

In this double-blind crossover study, the effects of bolus infusions of 0.9% saline (NaCl) and Hartmann's solution on serum albumin, haematocrit and serum and urinary biochemistry were compared in healthy subjects. Nine young adult male volunteers received 2-litre intravenous infusions of 0.9% saline and Hartmann's solution on separate occasions, in random order, each over 1 h. Body weight, haematocrit and serum biochemistry were measured pre-infusion and at 1 h intervals for 6 h. Biochemical analysis was performed on pooled post-infusion urine. Blood and plasma volume expansion, estimated by dilutional effects on haematocrit and serum albumin, were greater and more sustained after saline than after Hartmann's solution (P0.01). At 6 h, body weight measurements suggested that 56% of the infused saline was retained, in contrast with only 30% of the Hartmann's solution. Subjects voided more urine (median: 1,000 compared with 450 ml) of higher sodium content (median: 122 compared with 73 mmol) after Hartmann's than after saline (both P =0.049), despite the greater sodium content of the latter. The time to first micturition was less after Hartmann's than after saline (median: 70 compared with 185 min; P =0.008). There were no significant differences between the effects of the two solutions on serum sodium, potassium, urea or osmolality. After saline, all subjects developed hyperchloraemia (105 mmol/l), which was sustained for6 h, while serum chloride concentrations remained normal after Hartmann's (P0.001 for difference between infusions). Serum bicarbonate concentration was significantly lower after saline than after Hartmann's (P =0.008). Thus excretion of both water and sodium is slower after a 2-litre intravenous bolus of 0.9% saline than after Hartmann's solution, due possibly to the more physiological [Na(+)]/[Cl(-)] ratio in Hartmann's solution (1.18:1) than in saline (1:1) and to the hyperchloraemia caused by saline.

OBJECTIVE: The validity of the SCOFF delivered orally as a screening tool for eating disorders has previously been established, but clinical screening for eating disorders also occurs via written format, for example, in occupational health settings. The objective was to compare responses to the SCOFF between verbal and written administration. METHOD: In a volunteer group of nursing and midwifery students at a South London University SCOFF was delivered orally at interview and via written questionnaire. Order was allocated randomly with repeat administration interrupted by distraction questions. RESULTS: There were 185 students who participated, providing 178 fully completed responses. Twenty subjects were male. There was overall agreement in the scores of 157 subjects (88.2%), providing a kappa coefficient of 0.811, with agreement in prediction of eating disorder for 167 (93.8%) and a kappa value of 0.824 (both p < 0.001). For 82 subjects administered the SCOFF verbally first followed by the written version, the kappa statistic was 0.752 (p < 0.001). For 96 subjects with SCOFF administered in reverse order (written form first), kappa was 0.862 (p < 0.001). DISCUSSION: Results demonstrated overall good replicability of the SCOFF administered as a written questionnaire compared to oral interview. Two trends were noted. The first was towards higher scores with written versus oral delivery irrespective of order, possibly indicating enhanced disclosure via written format. The second was of less consistency where verbal preceded written responses. Altogether findings support use of the SCOFF where a concise, valid and reliable screening for eating disorders is required in written form.

Standards 2 and 3 of the national service framework for mental health outline the need to improve health care for patients with anorexia nervosa and bulimia nervosa.1 Healthcare workers in primary care are at the forefront of screening and managing these disorders. Assessment tools available to primary healthcare professionals can take a long time to administer and may need to be interpretedby specialists2; this may limit improvements in care. A screening tool was developed, but only to facitate epidemiological research.3 The SCOFF questionnaire is a brief and memorable tool designed to detect eating disorders and aid treatment (see figure). It showed excellent validity in a clinical population and reliability in a student population. 4 5 We assessed the SCOFF questionnaire in primary care. We invited sequential women attenders (aged 18-50) at two general practices in southwest London to participate. We gave participants …

Objective: To investigate possible inequities in the use of statins for people with coronary heart disease according to a wide range of social and clinical factors. Design and setting: Cross sectional analysis of data from the Health Survey for England 1998, a population based survey. Subjects: 760 adults with coronary heart disease. Results: Only 19.9% of subjects with coronary heart disease were receiving lipid lowering drugs (151 of 760; 95% confidence interval (CI) 17.0% to 22.7%). The likelihood of receiving statins was greatly reduced for older age groups: compared with those aged less than 65 years, the odds of receiving statin treatment were 0.53 (95% CI 0.35 to 0.80) for subjects aged 65–74 years, and 0.11 (95% CI 0.06 to 0.21) for subjects aged 75 years and over. Statins were given less often to current cigarette smokers than to non-smokers (odds ratio 0.55, 95% CI 0.32 to 0.96), and to subjects with angina compared with those with a previous myocardial infarct (odds ratio 0.63, 95% CI 0.43 to 0.93). Lower levels of statin use were also seen with increasing time since diagnosis (p = 0.12). No clear associations were observed with social measures. Conclusions: Important inequalities were found in the use of statins among people with coronary heart disease, which could not be justified by evidence from the large statin trials. Proactive policies are required to ensure that the vast majority of (if not all) patients with coronary heart disease are receiving statins, regardless of age, sex, social class, smoking status, type of coronary heart disease, or time since diagnosis.

A previous report on heart rate (HR) turbulence showed its value in postinfarction risk stratification. The present study determines the predictive value of HR turbulence in a low-risk population after acute myocardial infarction and provides insight into its pathophysiologic correlates. With use of the database of the The Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI) study, data were obtained from 1,212 survivors with a mean duration of follow-up of 20.3 months. The a priori end point was defined as the combination of fatal cardiac arrest and nonfatal cardiac arrest. HR turbulence characterized by turbulence onset (TO) and turbulence slope (TS) was calculated and correlated with baroreflex sensitivity (BRS) and the SD of the normal-to-normal RR intervals (SDNN). A composite index of cardiac autonomic function was assessed by combining HR turbulence (TO and TS), BRS, and SDNN. Both TO and TS correlated moderately but significantly with BRS and SDNN (r = 0.26 to 0.44, p