Bolton NHS Foundation Trust

OBJECTIVE: To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer. DATA SOURCES: Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies. REVIEW METHODS: Review of RCTs of omega 3 intake for (3) 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate. RESULTS: Of 15,159 titles and abstracts assessed, 48 RCTs (36,913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded. CONCLUSION: Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.

Aims: To develop and validate a short recovery questionnaire in collaboration with service users. Method: 126 people with experience of psychosis were recruited via the National Health Service (NHS) Trust and self‐help organisations nationwide. Items were generated from in‐depth interviews into recovery and developed into a 25‐item self‐report questionnaire. Data were factor analysed, and a final 22‐item measure (the QPR) was tested for reliability and validity. To assess validity the QPR was administered together with measures of: psychological distress (the General Health Questionnaire – GHQ); empowerment (the Making Decisions and Empowerment Scale – MDES), and quality of life (the Schizophrenia Quality of Life Scale – SQLS). The QPR was administered again at two weeks to assess reliability. Results: The QPR is comprised of two subscales (intrapersonal and interpersonal). Internal consistency and reliability of the scale was satisfactory. There was a high level of association with MDES, GHQ and SQLS scores, and between QPR scores at time one and time two. Conclusions: The QPR possesses internal consistency, construct validity and reliability, and promises to be a useful tool for assisting clients to set goals, evaluation of these goals and promoting recovery from psychosis in routine service evaluation and research trials.

These Joint British Diabetes Societies guidelines, commissioned by NHS Diabetes, for the perioperative management of the adult patient undergoing surgery are available in full in the Supporting Information. This document goes through the seven stages of the patient journey when having surgery. These are: primary care referral; surgical outpatients; preoperative assessment; hospital admission; surgery; post-operative care; discharge. Each stage is given its own considerations, outlining the roles and responsibilities of each group of healthcare professionals. The evidence base for the recommendations made at each stage, discussion of controversial areas and references are provided in the report. This document has two key recommendations. Firstly, that the management of the elective adult surgery patients should be with modification to their usual diabetes treatment if the fasting is minimized because the routine use of a variable rate intravenous insulin infusion is not recommended. Secondly, that poor preoperative glycaemic control leads to post-outcomes and thus, where appropriate, needs to be addressed prior to referral for surgery.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

PURPOSE: The purpose of this paper is to show how over the last 18 months Bolton Hospitals NHS Trust have been exploring whether or not lean methodologies, often known as the Toyota Production System, can indeed be applied to healthcare. DESIGN/METHODOLOGY/APPROACH: This paper is a viewpoint. FINDINGS: One's early experience is that lean really can save lives. The Toyota Production System is an amazingly successful way of manufacturing cars. It cannot be simply translated unthinkingly into a hospital but lessons can be learned from it and the method can be adapted and developed so that it becomes owned by healthcare staff and focused towards the goal of improved patient care. ORIGINALITY/VALUE: Working in healthcare is a stressful and difficult thing. Everyone needs a touch of inspiration and encouragement. Applying lean to healthcare in Bolton seems to be achieving just that for those who work there.

BACKGROUND: Thyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes. METHODS: We conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation. RESULTS: The follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P = 0.74; absolute difference, -0.4 percentage points; 95% CI, -6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P = 0.14). CONCLUSIONS: The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.).

BACKGROUND: Delays to timely admission from emergency departments (EDs) are known to harm patients. OBJECTIVE: To assess and quantify the increased risk of death resulting from delays to inpatient admission from EDs, using Hospital Episode Statistics and Office of National Statistics data in England. METHODS: A cross-sectional, retrospective observational study was carried out of patients admitted from every type 1 (major) ED in England between April 2016 and March 2018. The primary outcome was death from all causes within 30 days of admission. Observed mortality was compared with expected mortality, as calculated using a logistic regression model to adjust for sex, age, deprivation, comorbidities, hour of day, month, previous ED attendances/emergency admissions and crowding in the department at the time of the attendance. RESULTS: Between April 2016 and March 2018, 26 738 514 people attended an ED, with 7 472 480 patients admitted relating to 5 249 891 individual patients, who constituted the study's dataset. A total of 433 962 deaths occurred within 30 days. The overall crude 30-day mortality rate was 8.71% (95% CI 8.69% to 8.74%). A statistically significant linear increase in mortality was found from 5 hours after time of arrival at the ED up to 12 hours (when accurate data collection ceased) (p<0.001). The greatest change in the 30-day standardised mortality ratio was an 8% increase, occurring in the patient cohort that waited in the ED for more than 6 to 8 hours from the time of arrival. CONCLUSIONS: Delays to hospital inpatient admission for patients in excess of 5 hours from time of arrival at the ED are associated with an increase in all-cause 30-day mortality. Between 5 and 12 hours, delays cause a predictable dose-response effect. For every 82 admitted patients whose time to inpatient bed transfer is delayed beyond 6 to 8 hours from time of arrival at the ED, there is one extra death.

Adult tracheostomy and laryngectomy airway emergencies are uncommon, but do lead to significant morbidity and mortality. The National Tracheostomy Safety Project incorporates key stakeholder groups with multi-disciplinary expertise in airway management. , the Intensive Care Society, the Royal College of Anaesthetists, ENT UK, the British Association of Oral and Maxillofacial Surgeons, the College of Emergency Medicine, the Resuscitation Council (UK) the Royal College of Nursing, the Royal College of Speech and Language Therapists, the Association of Chartered Physiotherapists in Respiratory Care and the National Patient Safety Agency. Resources and emergency algorithms were developed by consensus, taking into account existing guidelines, evidence and experiences. The stakeholder groups reviewed draft emergency algorithms and feedback was also received from open peer review. The final algorithms describe a universal approach to managing such emergencies and are designed to be followed by first responders. The project aims to improve the management of tracheostomy and laryngectomy critical incidents.

BACKGROUND: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. METHODS: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5-12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0-94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96-1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of -0·040 (95% central range -0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. INTERPRETATION: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

BACKGROUND: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. METHODS: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. INTERPRETATION: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. FUNDING: National Institute for Health Research Health Technology Assessment programme.

A colorectal polyp is an abnormal protrusion of the mucosa into the bowel lumen that is classified by histopathological examination (Fig. 1). Adenomas are a common finding during colonoscopy in symptomatic patients and in asymptomatic individuals undergoing screening. It is estimated that the prevalence of large-bowel adenoma is 21–28% in 50–59-year-old subjects, increasing to 40–45% in 60–69-year-old subjects and rising further to 53–58% in people over the age of 70 1. Adenomas are important as they are the precursor lesion of most colorectal cancers arising through the adenoma–carcinoma sequence 2. This association is supported by epidemiological, clinical and molecular research 3. Whilst most polyps removed are small, it is well recognized that the risk of malignant transformation increases with increasing polyp size. There is compelling evidence that removing adenomas from the colon substantially reduces the risk of a patient developing colorectal cancer 4. The term 'malignant polyp' refers to an adenoma that appears benign macroscopically but in which there is invasion through the muscularis mucosae into the submucosa. Such a focus of carcinoma is detected on histological examination. A malignant polyp is therefore an early carcinoma. It accounts for 0.75–5.6% 5-9 of large-bowel polyps removed in general diagnostic colonoscopy practice. The wide discrepancy is explained by differences in the study populations, being lower where all polyps removed are histologically assessed and higher in series that only include larger polyps. In the Nottingham Bowel Cancer Screening Trial, 1466 patients underwent colonoscopy because of a positive faecal occult blood-test result. Of these, 710 (48%) were found to have an adenoma and a further 73 (5%) had an adenoma containing a focus of cancer 10. A similar incidence of malignant polyps has been found in the National Bowel Cancer Screening Programme. Of the first 1-million individuals screened, just over 17 000 had a positive faecal occult blood-test result. Of these, 1574 (9%) had cancer of which 155 (10%) were malignant polyps 11. In recent years, greater use of diagnostic colonoscopy has been accompanied by a rise in the number of malignant polyps removed endoscopically 12. The management of a malignant polyp following endoscopic removal is difficult because the possibility of residual malignant cells within the bowel wall or positive regional lymph nodes varies from patient to patient, depending on a number of prognostic factors. The evidence base for management of these lesions is poor and is mostly based on data from symptomatic patients 6, 13, 14. Advising patients on the course of action after removal is difficult. It includes surveillance only, where the risk of residual disease is deemed to be low, or major surgical resection for those with a higher risk. However, the level of risk is often difficult to calculate. Furthermore, the presence of comorbidity and the site of the lesion should also be considered when discussing further management with the patient. This position statement deals with a number of matters relating to the management of patients with a malignant polyp. It is divided into four sections. The first section considers colonoscopy and includes a discussion of endoscopic techniques for the removal of larger adenomas, which are more likely to be malignant. The influence of polypectomy technique on histopathological assessment and the regimens for postresection endoscopic surveillance are discussed. The second section reviews the histopathology of adenomas and polypoid carcinomas and considers important prognostic indicators. The third section deals with how the prognostic indicators influence the risk of residual cancer in the bowel wall or lymph nodes to estimate the likelihood of recurrence if no further treatment is undertaken. The traditional advice for a 'high-risk' adenoma was to advise a radical 'cancer' segmental colectomy, including the lympho-vascular pedicle. The fourth section discusses the balance of the risk of morbidity and mortality following endoscopic resection against the risk of recurrence and how this risk is communicated to the patient. Finally, the role of endoscopic and radiological imaging in the assessment and follow up of malignant polyps is considered, particularly where radical surgery is not performed. This also includes a discussion of the optimal follow-up protocol. Searches of the Cochrane Database, PubMed, MEDLINE and Embase were performed using keywords relevant to each section of the position statement. They were mostly limited to English-language articles. Additional publications were retrieved from references cited in articles identified from the primary search. All evidence was classified according to an accepted hierarchy of evidence, and recommendations were graded from A to C on the basis of the level of associated evidence and/or noted as Good Practice and/or part of the National Institutes of Clinical Excellence/ Scottish Intercollegiate Guidelines Network (NICE/SIGN) recommendation or Rapid Technology Appraisal (Table 1)15. Modern endoscopic practice is safe, thorough and offers extensive opportunities for identification, diagnosis and definitive management of most benign colorectal neoplasms. A small proportion of these will be early cancers, and the diffusion of colorectal cancer screening has led to more of these being discovered 16. The purpose of this section is to illustrate how, with proper location and characterization of colorectal neoplasms, malignant lesions can be detected and treated optimally by endoscopy alone when appropriate. This should reduce the number of 'surprise' malignant polyps and the clinical dilemmas they cause. It will reduce the necessity for surgery for inadequately treated polyps. Surgery can then be targeted on lesions with a high risk of local recurrence, lymph node metastasis and colorectal cancer death 17. The prerequisite for colonoscopy is a safe, complete examination of the entire colon and rectum. Great strides have been made in the completeness and accuracy of UK colonoscopy since the survey carried out by Bowles et al. 18 showed variable performance and unsatisfactory caecal intubation and complication rates and low levels of colonoscopy training. Re-audit following investment in training, accreditation and setting of quality assurance standards has demonstrated great improvements in examination quality, diagnostic accuracy and the safety of colonoscopy in the UK 19. Quality colonoscopy optimizes the chance of finding pathology. White light examination (WLE) alone is usually sufficient to identify colonic abnormalities, but tandem colonoscopy shows that this may miss 22% of all adenomas and 2.1% of adenomas over 1 cm in diameter 20. Most malignant polyps are larger pedunculated or protruding sessile lesions. These are usually easy to see. An important minority of neoplasms is not truly polypoid, but flat or even depressed. These are harder to spot but carry a much greater risk of malignancy. The challenge is to find these lesions. Good bowel preparation, meticulous mucosal washing, insufflation and careful inspection are critical 21. The flexures and inner angles of colonic folds are sites where there is a higher risk of lesions being missed and they require more careful inspection. Modern endoscopes have better bending sections, allowing retroflexion in the caecum and rectum to view the caecum beyond the ileocaecal valve and distal rectum. Right-sided colonic lesions are easier to miss because they tend to be flatter. Missed right-sided lesions may explain why colonoscopic screening has failed to make the hoped-for impact on the detection of right-sided colonic cancer 22. Patient repositioning during the examination, with the inspected flexure uppermost to open up collapsed areas, increases luminal distension 23 and adenoma detection 24. The time spent inspecting the mucosa (the withdrawal time) should be sufficient to allow a thorough mucosal view. The influence of a careful examination technique is highly significant for detection. Barclay et al. 25 found that colonoscopists who took longer than 6 min in the withdrawal and inspection phase had a higher detection rate for any neoplasm (28.3% vs 11.8%) and for advanced neoplasms (6.4% vs 2.6%) than those with a shorter inspection time. The adenoma detection rate (ADR) is a surrogate marker of the quality of colonoscopy and can therefore be used as a comparative measure in studies. Kaminski et al. 26 used the Polish bowel cancer screening data set to validate ADR as a quality indicator. They showed that an individual endoscopist's ADR is associated with the subsequent interval cancer risk, with a lower ADR predicting significantly higher interval cancer risk. Findings The quality of colonoscopy can be monitored using the adenoma detection rate and is enhanced by excellent preparation and meticulous technique. During withdrawal, inspection for more than 6 min and patient repositioning increases the adenoma detection rate, which is a reproducible quality marker (Level IIa). Recommendations Attention to preparation and endoscopic technique, especially the inspection (withdrawal) phase, will increase the quality of the examination and detection of pathology (Grade B). Polyps may be missed, either because they are subtle by being small, flat or depressed, or because they hide behind folds and flexures. Dye spray chromoendoscopy uses contrast reactive dyes, such as indigocarmine, to enhance mucosal features. At concentrations of 0.1–0.8%, indigocarmine fills cavities, pits and grooves in the mucosa and even flat, small polyps will be detected. Chromoendoscopy has been shown to increase the ADR but it is awkward and time consuming for use in routine practice. Other vital or absorptive dyes, such as crystal violet or methylene blue, are actively absorbed into the intestinal crypts, where they stain the convex portions but not the grooves. Very detailed magnification views are possible, but these dyes are slow to absorb and messy to use. A Cochrane collaborative review comparing white light and chromoscopic detection of colorectal neoplasia showed significantly enhanced detection of neoplasms using chromoendoscopy 27, 28. Most of the extra adenomas seen were diminutive, and more patients were found to have multiple polyps. Histology of these extra adenomas showed mostly low-grade dysplasia: this, plus the time to perform dye spray, has prevented pancolonic chromoscopy from becoming routine. Selective application of dye spray to areas of subtle mucosal change is valuable and can detect a higher number of neoplasms and help differentiate neoplastic from non-neoplastic lesions 29. Chromoendoscopy has a valuable place in detecting dysplasia in ulcerative colitis surveillance 30. Findings Dye spray chromoendoscopy enhances detection of colonic pathology, differentiation of neoplastic and non-neoplastic lesions and of dysplasia in inflammatory bowel disease (Level I). Recommendations Endoscopists should selectively use dye spray chromoendoscopy as it enhances detection and differentiation of colonic pathology (Grade A). Optical and processor-based technologies are near-instant methods to examine the mucosa to delineate polyps. There are no clear data to indicate that these methods increase the adenoma-detection rate but they have proven ability to characterize polyps once found 31. Narrow band imaging (NBI; marketed by Olympus), multiband imaging (MBI) (marketed as FICE – flexible spectral imaging colour enhancement; Fujinon) and i-scan (Pentax) manipulate the wavelengths of light used to examine the mucosa. NBI uses a real-time optical filter to select two or three restricted wavelengths of light to emphasize the mucosal microvasculature and identify vascular alterations associated with pathological conditions. FICE and i-scan are postprocessor technologies that recreate the image as per the desired wavelengths to enhance mucosal surface patterns. Autofluorescence imaging (AFI; marketed by Olympus) uses tissue-component responses to specific short and ultraviolet wavelengths, the characteristics of which are different in neoplasms. Because these technologies are based on different endoscope platforms, UK endoscopists rarely have a choice of technology. There is doubt whether NBI, FICE, i-scan or AFI improve the ADRs compared with good white light colonoscopy (WLC) in average-risk patients. Rex and Helbig 32 found no additional benefit with NBI compared with an expert using WLE. Adler et al. 33 found a nonsignificant trend for NBI for adenoma detection. In higher-risk patients under surveillance for hereditary nonpolyposis colorectal cancer (HNPCC), East et al. 34. showed significantly improved adenoma detection – typically subtle flat adenomas. A recent Cochrane review found no evidence that NBI is better than high-definition WLC at detecting adenomas, but NBI was better than standard-definition WLC and equal to high-definition WLC 35. A study by Kuiper et al. 36 compared adenoma-detection rates and polyp characterization using high-definition white light, AFI and NBI. There was no improvement in detection using these technologies over WLE but they proved sensitive and specific in differentiating neoplastic and non-neoplastic lesions. It is this property – and the speed of switching mode – that makes these systems valuable. Training and practice are critical for these techniques to be clinically valuable in everyday use; training programmes are being developed 37. Findings A careful, expert white light examination of the colon can be augmented by selective or targeted chromoscopy and/or optical enhancement to examine suspicious areas (Level I). Recommendations Techniques that enhance surface and vascular patterns of colonic lesions should be used in routine practice. Endoscopists should learn to interpret these imaging methods (Grade B). Cap colonoscopy – fitting a standard endoscope with a disposable hood or cap, can be used to improve exposure of hidden mucosa. The capped endoscope can be flexed against haustral folds, flattening them. A better view of the mucosa beyond the fold can then be obtained. Westwood et al. 38 recently reviewed published experience with this technique and found an increase in polyp detection and caecal intubation rates. As yet there is no reliable way to accurately predict malignant change in a polyp, but there are features of polyp size, shape, consistency, surface and vascularity that should alert the endoscopist to possible malignancy. Combining sophisticated imaging modalities may eventually provide an 'optical biopsy' 39. Knowledge and accurate use of these descriptive methods allows malignant risk stratification. The Erlangen Group 40 examined 11 188 adenomatous polyps in a European series from 1978 to 1993. Using multivariate analysis they related malignant risk to a number of features – both within the patients themselves (age and sex) and related to the multiplicity, site, size and histological type of polyps. Polyps < 5 mm in diameter carry negligible risk of malignancy, whereas those with a diameter of more than 25 mm carry a considerable risk (Table 2). There are problems with estimating size in vivo. A useful guide is that an open standard biopsy forcep width is 8 mm, while a closed forcep width is 2.5 mm. Endoscopists must practise taking such measurements. The site of a polyp within the colon is also a risk factor where proximal colonic polyps are, size for size, at greater risk of containing malignancy 41 (Table 3). The malignant risk for adenomas in the right colon (proximal to the splenic flexure) was higher than that for similar-size left-sided or rectal polyps. Increasing use of positional imaging technology allows more reliable description of lesion position in the colon – which can otherwise be inaccurate. Simple pattern recognition and experience are important. Malignancy is more likely when the contour is irregular, when there is ulceration or when the consistency of the polyp (when probed gently) is hard or when the stalk broadens 42. These classical signs are not always evident, and more sophisticated classifications have been developed. Lesions called 'flat' are rarely completely flat. The Paris Classification defines 'flat' as < 2.5 mm in height above the mucosa, which is the width of closed, standard endoscopic biopsy forceps. The category not specifically classified in the Paris Classification is the lateral spreading tumour (LST); in Europe and USA these are carpet adenomas. LSTs are flat adenomas larger than 10 mm in diameter that extend circumferentially and laterally rather than vertically. They may have a granular (LST-G) or a nongranular (LST-NG) surface. Nodules and depressed areas are seen within these lesions. They have a malignant potential that is not predicted solely by size but rather by the presence of nodules or depressed areas within them. The cancer risk in LST varies between 7% (LST-G) and 14% (LST-NG): the Paris Classification defines these as type 0-IIa 47. Table 4 shows the frequency of lesions classified by the Paris system related to both their size and the rate of submucosal invasion. The data are from Kudo, using the Paris system and include colon and rectal lesions 45. Classical protuberant lesions (0-Ip and 0-Is) are common, and size influences invasive risk: lesions of 5 mm or less are associated with negligible risk, but for lesions over 20 mm the risk of malignancy is high. Recognition of depression (type 0-IIc) in colorectal lesions is critical as this is often associated with invasive cancer, even when the lesion is small (< 10 mm). These true depressed lesions are rare but grow rapidly, become advanced at an early stage of the evolution of their growth and are seldom suitable for endoscopic resection. Initial clues are irregularities in mucosal appearances such as 'pinkness, minute depressions and/or haemorrhagic spots' 44. Because they are subtle, dye spray chromoendoscopy with indigocarmine is invaluable to demarcate them from background innominate grooves and delineates the surface, edge and any areas of depression. The colonoscope technologies NBI and FICE perform similar et al. chromoendoscopy with indigocarmine plus magnification of the – a not in the Polyps with more submucosal invasion – and – to have an depression with of the depressed surface and two or more Such are subtle in expert are highly of invasion they are difficult to into standard practice. a time there was doubt that flat polyps in because they were not being It is clear they and are being detected. The a series of and found adenomas these were a number of flat polyps and a small number of true depressed lesions with significant malignant Table 5 is from their data and in a from a that not only flat and depressed polyps but also that they can be detected in a UK and it the small, but risk of early cancer in polyps < 1 cm in as well as the greater risk with flat lesions of more than 1 cm in lesions are rare but et al. data from in where of cancers found by colonoscopy were of flat and small mm in The Bowel Cancer Screening all polyps to be classified by an endoscopist using the Paris Findings size and polyp all influence assessment of malignancy in a The Paris Classification is both descriptive and (Grade Recommendations Endoscopists should estimate size of polyps and use the Paris Classification to the of malignancy (Level A). inspection of the surface of polyps can further predict Chromoendoscopy using indigocarmine, with colonoscopy can flat or depressed lesions and identify the pattern of polyps that predict pathology. The Classification of patterns is shown in pattern and are non-neoplastic or polyps can to the adenoma and should be treated patterns and are most likely to be benign adenomas with a low risk of submucosal invasion. patterns indicate a high risk for invasion into at the submucosa. The pattern can further be divided into pits of and pits are This is only with pattern may be on the surface of a benign lesion but submucosal invasion can also has the likelihood of malignancy. Using this and related pattern with to of polyps. Table 6 their The ability to identify patterns the endoscopist to predict malignant change within a polyp and select et al. used a of and colonoscopy with chromoendoscopy to differentiate non-neoplastic and neoplastic lesions with and – it is not always to use pattern training and vascular pattern and mucosal pattern assessment with NBI allows diagnostic differentiation of non-neoplastic polyps from neoplastic polyps and will detect malignant change NBI detailed of the – the of this pattern has pattern to where type shows malignant In the type is into carcinoma and submucosal and with submucosal invasive cancer both magnification and considerable endoscopists use NBI to identify a neoplastic lesion and then dye spray to characterize the pattern rather than on the East et al. have demonstrated the of NBI with magnification in neoplasia in and in ulcerative NBI magnification can be as as the NBI system to be However, UK endoscopists not have to FICE is with and by detecting surface patterns can differentiation of polyp A is in a study by et al. FICE was shown to similar to NBI when using more a subsequent showed that FICE neoplastic and non-neoplastic polyps magnification et al. compared FICE with chromoscopy in small polyps and showed both modalities to have good and to neoplasia and Other methods of surface and lesion examination, as well as endoscopic are research or not sensitive or specific to be endoscopic into this in contrast with which is a routine in neoplastic particularly in with endoscopic Optical and endoscopy are being 39. A recent review and of that this offers diagnostic accuracy to colonoscopic histopathology in colorectal neoplasia This offers the possibility of in real-time optical biopsy in the is a by to enhance lesions difficult to by WLE. There as on in colorectal neoplastic characterization of malignant change or any a polyp can if there is submucosal with invasion A lesion to to the mucosa that or endoscopic resection will not be to clear the et al. in a small of patients found to with invasion – early cancers that were all or tumour invasion of the third and of the of the However, et al. used a with either or as the and compared this with endoscopic They found the to lower and accuracy compared with endoscopic for invasion vs and vs They that a lesion will be difficult to and of invasion more difficult to A of the is that submucosal makes a further at endoscopic at a more difficult by submucosal should be as a diagnostic to a for for as it makes less likely Findings characterization of polyp size, and surface pattern can predict histopathology of the lesion and allow of the risk of malignant change and of invasion. The submucosal invasion (Level I). Recommendations All colonoscopists should be with and use the Paris enhancement by chromoendoscopy and either NBI or FICE are to lesions being considered for advanced polypectomy techniques (Grade A). There is no in treatment for discussion with It is a to that optimal treatment is – and to an when is part of this of and/or with dye spray or techniques are for these an endoscopist can the patient or for of are becoming in the UK for such and and have proved in the USA and in There are a of techniques and these are to the type of polyp The should always where possible, an of the lesion in polypectomy is the of polyp management because the of lesions are size, position and can make this malignancy is within a pedunculated polyp the should be to the bowel to resection the and are polypectomy will be to in polyps may be and a of techniques are including application and polyps may be treated with polypectomy alone with that are but submucosal to enhance resection is routine. Most polypectomy of pedunculated malignant polyps if the from the invasive to is mm or more It offers the rate of local recurrence and and submucosal and mucosal resection or a submucosal with to the mucosa up in the submucosal of a over the entire lesion and the It allows flat or depressed lesions to be removed the lesion may be and using Modern in their and endoscopists must be with these when or left-sided lesions. The not only the but also as a There is no on which to use as a is but more such as or are to to only a is often to and dyes such as indigocarmine or methylene have been used to the of the the edge of the lesion and the of muscularis and can be in et al. 70 and et al. The of the lesion in and are critical for local

OBJECTIVE: The aims of the study were to report on the development and evaluation of a staff training intervention in dementia care designed for use in the general hospital setting: the 'Getting to Know Me' training programme. The study also aimed to undertake initial psychometric analysis on two new outcome scales designed to measure knowledge and confidence in dementia care. METHODS: The study comprised two phases. The first phase comprised the design of two questionnaires which are shared within this paper: Confidence in Dementia (CODE) Scale and Knowledge in Dementia (KIDE) Scale. In phase two, staff undertook the 'Getting to Know Me' training programme (n=71). The impact of the programme was evaluated using a pre-post design which explored: (1) changes in confidence in dementia; (2) changes in knowledge in dementia; and (3) changes in beliefs about challenging behaviour. RESULTS: The psychometric properties of the CODE and KIDE scales are reported. Statistically significant change was identified pre-post training on all outcome measures. Clinically meaningful change was demonstrated on the CODE scale. CONCLUSIONS: The 'Getting to Know Me' programme was well received and had a significant impact on staff knowledge and confidence. Our findings add to a growing evidence base which will be strengthened by further robust studies, the exploration of the impact of staff training on direct patient outcomes, and further identification of ways in which to transfer principles of care from specialist dementia environments into general hospital settings.

There has been significant advancement in virtual reality (VR) technology since its conception in 1960, and this evolution has particularly accelerated in recent years. Alongside this, we are seeing an expansion of research interest within which the definitions and nomenclature can be complex and lead to potential misunderstanding or confusion. We present a systematic review of definitions of the term VR as reported within the medical literature with the aim to establish the terminology used to define VR, the differences that exist through the literature, and if they have changed over time. By reporting according to the PRISMA guidelines, we present a systematic review of VR definitions in the English language medical literature. The databases Medline, PubMed, Web of Science, and Scopus were searched using the search terms ‘virtual reality’, ‘definition’, ‘defined’, or ‘define’. Articles were included if they were peer-reviewed, within the medical literature, published between 22nd December 2001 and 22nd December 2021, and offered either an original or cited definition for the term VR. Following data extraction, quantitative analysis of terminology over time and term density maps have been created. Eighty-eight studies were included offering 105 definitions of the term VR. Of these articles, 58 were published within the last 5 years. Common terms when defining VR included ‘computer’, ‘environment’, ‘user’, ‘interactive’ and ‘simulation’. In recent years, a novel term ‘head mounted display’ has emerged which was not previously featured in healthcare literature. This systematic review highlights that the published literature in the field of VR is rapidly expanding. With the growth in technology we can see a complex network of terminology emerge with little homogeneity. Definitions of VR are numerable and high variability exists. We recommend the requirement for consensus in order to urgently unify terminology within the immersive technology field, and whilst waiting for agreement, an evidence-based definition for VR has been suggested. A systematic review of the literature has been performed to better understand the terminology that academic authors have used to define what virtual reality technology is. This review concluded that a wide range of definitions have been used in the last 20 years. Throughout these definitions a large number of individual terms are being used with very little agreement on their appropriate use. With rapidly expanding technology and increasing complexity within the terminology, future research is at risk of misrepresentation until the academic community agree on the most appropriate terminology to be used when defining VR.

OBJECTIVE: To assess the effectiveness of a primary care referral scheme on increasing physical activity at 1 year from referral. Design Two-group randomized controlled trial recruiting primary care referrals to a borough-based exercise scheme. Setting A local authority borough in the north-west of England. Participants 545 patients defined as sedentary by a primary care practitioner. Intervention Referral to a local-authority exercise referral scheme and written information compared with written information only. Main outcome measures Meeting physical activity target at 12 months following referral, with a secondary outcome measured at 6 months from referral. RESULTS: At 12 months, a non-significant increase of 5 per cent was observed in the intervention compared with control group, for participation in at least 90 minutes of moderate/vigorous activity per week (25.8 versus 20.4 per cent, OR 1.45, 0.84 to 2.50, p = 0.18). At 6 months, a 10 per cent treatment effect was observed which was significant (22.6 versus 13.6 per cent, OR 1.67, 1.08 to 2.60, p = 0.05). The intervention increased satisfaction with information but this did not influence adherence with physical activity. CONCLUSION: Community-based physical activity referral schemes have some impact on reducing sedentary behaviour in the short-term, but which is unlikely to be sustained and lead to benefits in terms of health.

Relatives play a key role in supporting people with psychosis at all stages of recovery, but this can be associated with high levels of distress. Family interventions, with an international evidence base, improve outcomes for service users but little is known about their impact on relatives' outcomes. This review of published evaluations aimed to assess whether family interventions are effective in improving outcomes for relatives of people with psychosis, to identify the key components of effective intervention packages, and to identify methodological limitations to be addressed in future research. Fifty studies were identified which evaluated an intervention to support relatives against a control group, and in which outcomes for the relatives were reported. Thirty (60%) studies showed a statistically significant positive impact of the intervention on at least one relatives' outcome category. Eleven key intervention components were identified across all 50 studies, but there was no evidence that the presence or absence of any of these key components reliably distinguished effective from ineffective interventions. Methodological quality of studies was generally poor with only 11 studies rated as adequate using the Clinical Trial Assessment Measure (CTAM). Recommendations to improve future research include larger samples; better defined interventions and controls; true randomisation and blind assessors; clearly specified primary outcomes; pre-published analysis plans that account appropriately for missing data and clustering of data; a consensus on the most relevant outcomes to assess and valid and reliable measures to do so. Alternative research designs need to be considered to evaluate more recent approaches which focus on family support, personalised to meet individual need, and offered as an integral part of complex clinical services.

1. Depression 2. Neuropsychological Tests 3. Neuropsychiatric Assessments 4. Activities of Daily Living 5. Global Assessments/Quality of Life 6. Global Mental Health Assessments 7. Physical Examination 8. Delirium 9. Caregiver Assessments 10. Memory Functioning 11. Other Scales 12. Appendix 1: What to Use and When 13. Appendix 2: Additional Scales 14. Scales Index

Several risk factors for the development of cataract have been identified. This review evaluates epidemiologic literature that has examined tobacco smoking as a risk factor for cataract formation using established causality criteria. Twenty-seven studies were included in this review. Evidence suggests that smoking has a 3-fold increase on the risk for incident nuclear cataract development. There was also evidence of dose response, temporal relationship, and reversibility of effect. There was limited evidence of an association between smoking and posterior subcapsular cataract, but little or no association with cortical cataract. Thus, the literature review indicated a strong association between smoking and the development of cataract, particularly nuclear cataract. The association fulfills the established criteria for causality. The association between smoking and other types of cataract is less distinct and requires further evaluation.

BACKGROUND: There is a vast array of scales available to assess all aspects of mental and physical health in older people which may be of relevance to the work of old age psychiatrists. AIMS: To summarise some of the scales that may be commonly used in clinical and research practice and to give the reader guidelines as to where further information can be obtained. METHOD: The scales were selected on the basis of the authors' own clinical and research knowledge and information was gathered from a comprehensive text on assessment scales in old age psychiatry. Results The selected scales are described in brief and a table outlines the purposes for which they are most suitable. CONCLUSIONS: Although many scales are available, the choice of the individual scale relies specifically on the question that is to be asked. The ideal scale does not exist.

BACKGROUND: There is no consensus agreement regarding optimal management of locally excised ductal carcinoma in situ (DCIS) or features of greatest assistance in predicting disease behaviour. Cases in the UKCCCR/ANZ DCIS trial have been histologically reviewed to determine the features of prognostic importance. METHOD: A total of 72% of 1694 cases entered into the UKCCCR/ANZ DCIS trial had full pathological review. A large number of histological features were assessed, blinded to outcome and compared regarding ability to predict ipsilateral recurrence, as either DCIS or progression to invasive carcinoma. RESULTS: Pathological features associated with ipsilateral recurrence in univariate analysis included high cytonuclear grade, larger lesion size, growth pattern, presence of necrosis or chronic inflammation, incompleteness (or uncertainty of completeness) of excision and smaller margin width. Receipt of post-operative radiotherapy was also a strong prognostic factor.We report a novel sub-division of the large group of high-grade lesions, which enables identification of a very poor prognosis sub-group; namely, DCIS that is of high cytonuclear grade, predominantly (>50%) solid architecture, bearing extensive comedo-type necrosis (>50% of ducts). In addition, we found little difference in ipsilateral recurrence rates between low- and intermediate-grade groups. Hazard ratios for low, intermediate, high and the new, very high, grade were 0.42, 0.33, 0.62 and 1.00, respectively, for ipsilateral in situ or invasive recurrence. CONCLUSION: We present a novel pathological classification for DCIS with substantially better prognostic discrimination for ipsilateral recurrence than the classical categorisation based on cytonuclear grade alone.

Many people take dietary supplements, but information on characteristics associated with their use is lacking. The relationship between lifestyle behaviours, morbidity and use of dietary supplements has not been examined and earlier studies have limited applicability to a general population. These issues were addressed in the current study. Information was obtained by postal questionnaire sent to a sample of the general population. The questionnaire was completed by 70.5 % of the sample (15 465 from a total sample of 21 923), with at least one-third (35.5 %) taking dietary supplements. In adjusted analyses, supplement users were more likely to be women, white, home-owners, non-smokers and physically active. Use of vitamin, mineral and/or antioxidant supplements was associated with eating more fruits and vegetables, and taking fish-oil supplements was associated with eating oil-rich fish. A history of CVD or risk factors for CVD reduced the risk of taking vitamins, minerals and/or antioxidants or fish-oil supplements. Those reporting musculoskeletal disorders such as arthritis were more likely to take fish-oil supplements For the first time, we have shown that dietary supplement use is related to different types of morbidity. In particular, people at risk of primary or secondary CVD seem less likely to use dietary supplements, despite possible benefits shown in clinical trials. Public health organisations need to develop guidelines for the public and health professionals regarding the uncontrolled use of dietary supplements in the community.