Malignant melanoma of the gastrointestinal tract: symptoms, diagnosis, and current treatment options.

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments

A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn’s disease

Background: A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn’s disease. Methods: A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn’s disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn’s disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn’s, active Crohn’s, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model. Results: Pooled LMR in healthy controls was 0.014 (95% CI: 0.006–0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089–0.178) and 0.037 (95% CI: 0.019–0.055). In active and inactive Crohn’s disease, pooled LMRs were 0.093 (95% CI: 0.031–0.156) and 0.028 (95% CI: 0.015–0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn’s (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn’s (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn’s and inactive Crohn’s (SMD = 1.429 (95% CI: 0.580 to 2.278, p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies. Conclusion: The use of gut permeability measurements in screening and monitoring of coeliac and Crohn’s disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use

EndoBarrier®: a safe and effective novel treatment for obesity and type 2 diabetes?

BACKGROUND AND AIMS: Obesity associated with diabetes mellitus is a significant worldwide problem associated with considerable health care costs. Whilst surgical intervention is effective, it is invasive, costly and associated with complications. This study aims to evaluate the safety and efficacy of the EndoBarrier®, a duodenal-jejunal sleeve bypass as an alternative treatment of diabetes mellitus in obese patients. MATERIALS AND METHODS: This was a multi-centre, non-randomised trial recruiting obese patients with type 2 diabetes from three sites in the UK. Eligible participants had a BMI of 30-50 kg/m2and HbA1c levels of 7.5-10%. The study comprised a 12-month period with the EndoBarrier® inserted and a 6-month follow-up period after it had been explanted. The primary study outcomes were weight, BMI, HbA1c levels and fasting insulin and glucose levels. RESULTS: Forty-five patients were recruited and 31 patients (69%) completed the 12-month study period. Significant reductions in weight (95%CI 0.62-29.38; p < 0.05) and BMI (95%CI 1.1-8.7; p < 0.005) were documented 12 months after device insertion. The mean HbA1c was significantly reduced (95%CI 0.1-1.6; p < 0.05) after the device insertion period and reductions in metabolic parameters (fasting insulin and glucose levels) were also documented during the study. Adverse events were also assessed in all patients, the vast majority of which were reported as mild. CONCLUSIONS: The EndoBarrier® appears to be a safe and effective treatment strategy in overweight patients with poor glycaemic control despite medical therapy, or in those who are eligible but decline bariatric surgery

Challenges and improvement needs in the care of patients with central diabetes insipidus

Central diabetes insipidus (CDI) is a rare condition, with significant impact on patient health and well-being. It is a chronic condition which usually requires meticulous long-term care. It can affect both children and adults. There is limited literature considering the needs and challenges inherent in providing high quality care to patients with CDI, across the care pathway. This paper seeks to address this gap by providing a unique and well-rounded understanding of clinical and healthcare systems-related challenges. It draws on insights from the literature, from direct clinical experience contributed by five clinicians as co-authors (providing insights from France, Ireland, Italy, Spain and the United Kingdom), and from patient perspectives provided through interviews with patient representatives from three patient organisations. We identify clinical challenges related to the diagnosis of CDI, including differentiating between other similar conditions and determining the underlying aetiology. Treatment is challenging, given the need to tailor medication to each patient’s needs and ongoing management is required to ensure that patients continue to respond adequately to treatment. Ongoing support is required when patients switch between formulations. We also identify healthcare systems challenges related to limited awareness of CDI amongst primary care physicians and general paediatricians, and the need for highly skilled specialist care and appropriate workforce capacity. There is also a significant need for raising awareness and for the education of both healthcare professionals and patients about different aspects of CDI, with the aim of supporting improved care and effective patient engagement with healthcare professionals. We reflect on this information and highlight improvement opportunities. These relate to developing guidance to support patients, carers, primary care physicians and general paediatricians to identify clinical features earlier, and to consider CDI as a possible diagnosis when a patient presents with suggestive symptom

Disinfection of the Access Orifice in NOTES: Evaluation of the Evidence Base

Introduction. Appropriate prevention of infection is a key area of research in natural orifice translumenal endoscopic surgery (NOTES), as identified by the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR). Methods. A review of the literature was conducted evaluating the evidence base for access orifice preparation/treatment in NOTES procedures in the context of infectious complications. Recommendations based on the Oxford Centre for Evidence-Based Medicine guidelines were made. Results. The most robust evidence includes several experimental randomised controlled trials assessing infectious complications in the transgastric approach to NOTES. Transvaginal procedures are long established for accessing the peritoneal cavity following disinfection with antiseptic. Only experimental case series for transcolonic and transvesical approaches are described. Conclusion. Grade C recommendation requiring no preoperative preparation can be made for the transgastric approach. Antiseptic irrigation is recommended for transvaginal (grade C) NOTES access, as is current practice. Further human trials need to be conducted to corroborate the current evidence base for transgastric closure. It is important that future trials are conducted in a methodologically robust fashion, with emphasis on clinical outcomes and standardisation of enterotomy closure and postoperative therapy

Developing young people's sense of self and place through sport

Previous research has recognized positive health implications, both physical and mental, as an outcome of participation in leisure pursuits. They provide opportunities for self-expression and stress reduction, as well as an environment in which people can socialize. Leisure activities, specifically sport activities, can play a significant role in young people's identity development. This paper explores the leisure activities in which young people in Adelaide, Australia participate. It examines the role of leisure activities in terms of young people's identity and feelings towards their hometown. This study consisted of semi-structured focus groups conducted with 24 senior high school students, followed by a survey resulting in 226 useable responses. Respondents were aged between 16 and 18 years of age. From the range of activities identified and explored, the results revealed sports activities to have the greatest impact on young people's lives. The results demonstrated that frequency of participation has a significant effect on young people's involvement levels and how they identify with the activity

Efficacy of a Topical Formulation Containing Emodepside and Praziquantel (Profender®, Bayer) against Nematodes in Captive Tortoises

Gastrointestinal parasites are commonly diagnosed in captive tortoises. In response, fenbendazole has traditionally been used as an anthelmintic, either in single or repeated doses. However, fenbendazole requires oral administration and the process can be very challenging in some individuals. A topical preparation containing emodepside and praziquantel (Profender®, Bayer, Leverkusen, Germany) is promoted as effective against a broad range of nematodes, trematodes, and cestodes. Although this product is currently only licensed for administration to cats, previous studies have shown positive results with tortoises. The aim of this study was to determine the efficacy of Profender against oxyurid and ascarid parasites in captive tortoises. This was achieved by quantifying nematode eggs per gram (EPG) in feces using a modified McMaster technique before (Day 0) and after (Days 14 and 33) topical application of Profender at a dose rate of 21.5 mg emodepside and 85.5 mg praziquantel per kilogram. Twenty-nine tortoises, representing four different species, were enrolled in this study of which 14 (48%; including Testudo hermanni and Testudo graeca) were positive for intestinal nematodes. Following treatment, the oxyurid EPG was slightly increased on Day 14 but declined significantly by Day 33 (59.7% reduction; P = 0.01), indicating a slow onset of effect and moderate efficacy 33 days posttreatment; however, no conclusions regarding efficacy against ascarids can be drawn from this study. Topical application of emodepside and praziquantel was well tolerated in our tortoise population and, therefore, could be considered as a useful alternative anthelmintic treatment protocol for captive tortoises

Increasing the frequency of hand washing by healthcare workers does not lead to commensurate reductions in staphylococcal infection in a hospital ward

Hand hygiene is generally considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, several researchers have found the law of diminishing returns to apply to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance, and others have demonstrated that poor cohorting of nursing staff profoundly influences the effectiveness of hand hygiene measures. Collectively, these findings raise intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI. In order to investigate these issues further, we constructed a deterministic Ross-Macdonald model and applied it to a hypothetical general medical ward. In this model the transmission of staphylococcal infection was assumed to occur after contact with the transiently colonized hands of HCWs, who, in turn, acquire contamination only by touching colonized patients. The aim of the study was to evaluate the impact of imperfect hand cleansing on the transmission of staphylococcal infection and to identify, whether there is a limit, above which further hand hygiene compliance is unlikely to be of benefit. The model demonstrated that if transmission is solely via the hands of HCWs, it should, under most circumstances, be possible to prevent outbreaks of staphylococcal infection from occurring at a hand cleansing frequencies <50%, even with imperfect hand hygiene. The analysis also indicated that the relationship between hand cleansing efficacy and frequency is not linear - as efficacy decreases, so the hand cleansing frequency required to ensure R0<1 increases disproportionately. Although our study confirmed hand hygiene to be an effective control measure, it demonstrated that the law of diminishing returns applies, with the greatest benefit derived from the first 20% or so of compliance. Indeed, our analysis suggests that there is little benefit to be accrued from very high levels of hand cleansing and that in most situations compliance >40% should be enough to prevent outbreaks of staphylococcal infection occurring, if transmission is solely via the hands of HCWs. Furthermore we identified a non-linear relationship between hand cleansing efficacy and frequency, suggesting that it is important to maximise the efficacy of the hand cleansing process

Simultaneous temporal trends in dementia incidence and prevalence, 2005–2013 : a population-based retrospective cohort study in Saskatchewan, Canada

Original studies published over the last decade regarding time trends in dementia report mixed results. The aims of the present study were to use linked administrative health data for the province of Saskatchewan for the period 2005/2006 to 2012/2013 to: (1) examine simultaneous temporal trends in annual age- and sex-specific dementia incidence and prevalence among individuals aged 45 and older, and (2) stratify the changes in incidence over time by database of identification. Using a population-based retrospective cohort study design, data were extracted from seven provincial administrative health databases linked by a unique anonymized identification number. Individuals 45 years and older at first identification of dementia between April 1, 2005 and March 31, 2013 were included, based on case definition criteria met within any one of four administrative health databases (hospital, physician, prescription drug, and long-term care). Between 2005/2006 and 2012/2013, the 12-month age-standardized incidence rate of dementia declined significantly by 11.07% and the 12-month age-standardized prevalence increased significantly by 30.54%. The number of incident cases decreased from 3,389 to 3,270 and the number of prevalent cases increased from 8,795 to 13,012. Incidence rate reductions were observed in every database of identification. We observed a simultaneous trend of decreasing incidence and increasing prevalence of dementia over a relatively short 8-year time period from 2005/2006 to 2012/2013. These trends indicate that the average survival time of dementia is lengthening. Continued observation of these time trends is warranted given the short study period