Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Googling Allergy in Ireland: Content Analysis.

BACKGROUND: Internet search engines are increasingly being utilized as the first port of call for medical information by the public. The prevalence of allergies in developed countries has risen steadily over time. There exists significant variability in the quality of health-related information available on the web. Inaccurately diagnosed and mismanaged allergic disease has major downstream effects on patients, general practitioners, and regional allergy services. OBJECTIVE: This study aimed to verify whether Ireland has a relatively high rate of web-based allergy-related searches, to establish the proportion of medically accurate web pages encountered by the public, and to compare current search results localized to Dublin, Ireland with urban centers elsewhere. METHODS: Google Trends was used to evaluate regional interest of allergy-related search terms over a 10-year period using terms "allergy," "allergy test," "food allergy," and "food intolerance." These terms were then inputted into Google search, localizing them to cities in Ireland, the United Kingdom, and the United States. Output for each search was reviewed by two independent clinicians and deemed rational or nonevidence based, as per current best practice guidelines. Searches localized to Dublin were initially completed in 2015 and repeated in 2019 to assess for changes in the quality of search results over time. RESULTS: Ireland has a persistently high demand for web-based information relating to allergy and ranks first worldwide for "allergy test," second for "food allergy" and "food intolerance," and seventh for "allergy" over the specified 10-year timeframe. Results for each of the four subsearches in Dublin (2015) showed that over 60% of websites promoted nonevidence-based diagnostics. A marginal improvement in scientifically robust information was seen in 2019, but results for "allergy test" and "food intolerance" continued to promote alternative testing 57% (8/14) of the time. This strongly contrasted with results localized to Southampton and Rochester, where academic and hospital-affiliated web pages predominantly featured. Government-funded Department of Health websites did not feature in the top five results for Dublin searches "allergy testing," "food allergy," or "food intolerance" in either 2015 or 2019. CONCLUSIONS: The Irish public demonstrates a keen interest in seeking allergy-related information on the web. The proportion of evidence-based websites encountered by the Irish public is considerably lower than that encountered by patients in other urban centers. Factors contributing to this are the lack of a specialist register for allergy in Ireland, inadequate funding for allergy centers currently in operation, and insufficient promotion by the health service of their web-based health database, which contains useful patient-oriented information on allergy. Increased funding of clinical allergology services will more meaningfully impact the health of patients if there is a parallel investment by the health service in information and communication technology consultancy to amplify their presence on the web.

A comparative study of short- and medium-term outcomes comparing emergent surgery and stenting as a bridge to surgery in patients with acute malignant colonic obstruction.

BACKGROUND: The use of self-expanding metal stents as a bridge to surgery in the setting of malignant colorectal obstruction has been advocated as an acceptable alternative to emergency surgery. However, concerns about the safety of stenting have been raised following recent randomized studies. OBJECTIVES: The aim of the current study was to compare outcomes. DESIGN: This was an observational, comparative study. SETTINGS: This study was conducted at a tertiary referral center and university teaching hospital. PATIENTS AND INTERVENTIONS: Patients with malignant colonic obstruction (n = 49) treated by either emergency surgery (n = 26) or with stent placement (n = 23) as a bridge to surgery were identified and followed. MAIN OUTCOME MEASURES: Short-term outcomes including stoma rates and postoperative morbidity and medium-term oncological outcomes were compared based on an "intention-to-treat" analysis. RESULTS: Patients in both groups were well matched on clinicopathological parameters. Technical and clinical successful stent deployment was achieved in 91% and 83%. This did not adversely impact cancer-specific and overall survival (log rank = nonsignificant). No difference was observed in stoma rates, primary anastomosis rates, perioperative mortality rates, or reoperation rates between the 2 groups. Significantly fewer patients underwent total colectomy in the stent group in comparison with the emergency surgery group (1/23 vs 6/26: p = 0.027). There was no difference in postoperative morbidity (59% vs 66%: p = 0.09). There was a significant reduction in readmission rates in the stent group (5/26 vs 0/23: p = 0.038). LIMITATIONS: The small sample size of this study could lead to type II error. In addition, the study was nonrandomized and demonstrated a limited length of follow-up. CONCLUSION: Despite a high rate of technical and clinical success in selected patients with colonic obstruction, stenting has no impact on stoma rates. Despite concerns about the rate of stent-associated perforation, stenting does not adversely impact disease progression or survival. Future comparative trials are essential to better define the role of stenting in this setting and to ensure that we are not using costly technology to create an elective operative situation without concomitant patient benefits.

The bowel and beyond: extracolonic findings from CT colonography.

CT colonography has emerged as the investigation of choice for suspected colorectal cancer in patients when a colonoscopy in incomplete, is deemed high risk or is declined because of patient preference. Unlike a traditional colonoscopy, it frequently reveals extracolonic as well as colonic findings. Our study aimed to determine the prevalence, characteristics and potential significance of extracolonic findings on CT colonography within our own institution. A retrospective review was performed of 502 patients who underwent CT colonography in our institution between January 1, 2010 and January 4, 2015. Of 502 patients, 60.63% had at least one extracolonic finding. This was close to other similar-sized studies (Kumar et al. Radiology 236(2):519-526, 2005). However, our rate of E4 findings was significantly higher than that reported in larger studies at 5.3%(Pooler et al. AJR 206:313-318, 2016). The difference may be explained by our combination of symptomatic/screening patients or by the age and gender distribution of our population. Our study lends support to the hypothesis that CT colonography may be particularly useful in identifying clinically significant extracolonic findings in symptomatic patients. CT colonography may allow early identification of extracolonic malignancies and life-threatening conditions such as an abdominal aortic aneurysm at a preclinical stage when they are amenable to medical or surgical intervention. However, extracolonic findings may also result in unnecessary investigations for subsequently benign findings.

Global prevalence of functional constipation according to the Rome criteria: a systematic review and meta-analysis.

BACKGROUND: Functional constipation is a common functional bowel disorder in the community, which has a varying prevalence across cross-sectional surveys. We did a contemporaneous systematic review and meta-analysis of studies using comparable methodology and all iterations of the Rome criteria to estimate the global prevalence of functional constipation. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Embase Classic from Jan 1, 1990, to Dec 31, 2020, to identify population-based cross-sectional studies comprising at least 50 participants that reported the prevalence of functional constipation in adults (age 18 years and older) according to Rome I, II, III, or IV criteria. We excluded studies that reported the prevalence of functional constipation in convenience samples. We extracted prevalence estimates of functional constipation from eligible studies, according to the study criteria used to define it. For each study, we extracted data for country; method of data collection; criteria used to define functional constipation; whether the study used the Rome I, II, III, or IV diagnostic questionnaires or approximated these definitions of the condition using another questionnaire; the total number of participants providing complete data; age; the number of participants with the condition; the number of male and female participants; and the number of male and female participants with the condition. We calculated pooled prevalence, odds ratios (OR), and 95% CIs. FINDINGS: Of 8174 citations evaluated, 45 studies fulfilled the eligibility criteria, representing 80 separate populations and comprising 275 260 participants. The pooled prevalence of functional constipation was 15·3% (95% CI 8·1-24·4, I2=99·4%) in studies using the Rome I criteria, 11·2% (7·9-14·9; I2=99·6%) in studies that used Rome II criteria, 10·4% (6·5-14·9; I2=99·8%) in those that used Rome III criteria, and 10·1% (8·7-11·6; I2=98·2%) when Rome IV criteria were used. Prevalence of functional constipation was higher in women, irrespective of the Rome criteria used (OR 2·40 [95% CI 2·02-2·86] for Rome I, 1·94 [1·46-2·57] for Rome II, and 2·32 [1·85-2·92] for Rome III; no studies using Rome IV criteria reported prevalence by sex). There was significant heterogeneity between studies in all of our analyses, which persisted even when the same criteria were applied and similar methodologies used. INTERPRETATION: Even when uniform symptom-based criteria are used to define the presence of functional constipation, prevalence varies between countries. Thus, environmental, cultural, ethnic, dietary, or genetic factors can influence reporting of symptoms. Future studies should aim to elucidate reasons for this geographical variability. FUNDING: None.

A case report of endovascular management of delayed upper gastrointestinal bleeding after open esophagectomy for a benign esophageal stricture.

INTRODUCTION: Delayed upper gastrointestinal (GI) bleeding is a rare complication of esophagectomy and can be difficult to manage. PRESENTATION: A 76-year-old female represented 17 days post open esophagectomy with an unstable upper GI bleed. When control could not be achieved endoscopically, she was transferred to the Radiology Department where a triphasic CT angiogram confirmed active contrast extravasation into the gastric tube. She proceeded to the Interventional Radiology suite where a thoracic angiogram revealed an active arterial bleed from a branch of the thyrocervical trunk. The bleeding vessel was successfully embolised with coils and haemostasis was achieved. DISCUSSION: Management options for upper GI bleeding post esophagectomy include medical, endoscopic and endovascular approaches. CONCLUSION: Our case represents a rare example of delayed bleeding into a gastric conduit post open esophagectomy for a benign stricture. The case reinforces.

Safety and efficacy of combining biologics or small molecules for inflammatory bowel disease or immune-mediated inflammatory diseases: A European retrospective observational study.

BACKGROUND AND AIMS: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series. METHODS: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life-threatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination. RESULTS: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients. CONCLUSIONS: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%.

Food-dependent exercise-induced reactions: lessons from a 15-year retrospective study.

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) is a life-threatening disorder in which the signs and symptoms of anaphylaxis occur if physical exertion occurs within a few hours of exposure to a food. AIMS: The aim of this study was to characterise patients diagnosed with FDEIA and related disorders. METHODS: A retrospective review of electronic clinical data from 2001 to 2016 was carried out. Fifty-seven cases were identified and analysed to establish clinical features, triggering factors and sensitisation patterns. RESULTS: The number of patients per annum diagnosed with FDEIA or related reactions increased from 1 in 2001 to 18 patients in 2016. Sixty-nine percent reported systemic symptoms consistent with anaphylaxis, and 31% had skin manifestations only. In 33% of cases, the level of triggering exercise was mild. Forty-four percent of patients were sensitised to the omega-5-gliadin fraction of wheat. CONCLUSIONS: FDEIA is an increasingly recognised serious allergic disease. The clinical diagnosis is supported by targeted sensitisation testing and molecular-based allergy diagnostics. These tools allow implementation of effective dietary and lifestyle modifications that mitigate against future serious reactions. Given the limited access to physicians with specialist allergy training in Ireland, increased awareness of this condition amongst sports medicine specialists and general physicians is required.

Predicting pathology on small bowel capsule endoscopy: a good FIT.

Background and study aims Small bowel capsule endoscopy [SBCE) has an established role in investigating suspected small bowel bleeding [SSBB). Identification of a biomarker to predict pathology would maximize utility of this valuable diagnostic modality. This study aimed to investigate if fecal immunochemical test [FIT) could predict likelihood of small bowel pathology on SBCE. Patients and methods Patients referred for SBCE to investigate anaemia or suspected small bowel bleeding were prospectively recruited. All patients had negative upper and lower endoscopy prior to referral. A FIT ≥ 45 ug Hb/g was considered positive. SBCE was positive if a potential source of SSBB was identified. The primary endpoint was correlation between FIT and positive SBCE. Secondary endpoints were correlation between anemia and SBCE and a combination of anemia plus FIT and SBCE. Results Fifty-one patients were included in the final study cohort. 29.4 % had a positive FIT, 33.3 % were anemic, and 25.5 % patients had significant SBCE findings. There was a statistically significant association between positive FIT and pathology on SBCE (OR 12, 95 % CI [2.8 - 51.9), P  = 0.001). Sensitivity and specificity of positive FIT in predicting SBCE findings were 69 % and 84 %, respectively. A normal Hb had an NPV of 83 % (OR 0.30, P  = 0.09). Combining Hb and FIT was statistically significant in predicting pathology on SBCE (OR 9.14, 67 % PPV, 82 % NPV, P  = 0.025). Conclusion FIT ≥ 45 ug Hb/g is a useful tool in predicting small bowel pathology on SBCE. Use of this biomarker alone, or in combination with serum haemoglobin, has value as a screening tool and may help to better triage patients referred for SBCE.

A Systematic Review of the Causes and Management of Nonthrombotic Embolic Stroke of Tissue Origin.

INTRODUCTION: Various bodily tissues have been reported to enter the arterial circulation and embolize to the brain resulting in ischemic stroke. Most frequently nonthrombotic embolic stroke (NTES) of tissue origin is iatrogenic or related to an underlying disease process. With the increase in elective surgery and intravascular procedures, NTES may increase in prevalence. AIM: To compile a summary of the background, incidence, presentation, and treatment of NTES of tissue origin, by conducting a systematic review of the current literature. SUMMARY OF REVIEW: We searched EMBASE and MEDLINE for articles on NTES of tissue origin published in English with no restriction on publication date (search date June 2017). 800 articles were identified and screened and 159 articles were ultimately reviewed in full text and included in qualitative analysis. Articles deemed relevant were assessed by a second reviewer to confirm compatibility with the inclusion criteria. References of included articles were reviewed for relevant publications. We categorized the pathology of the emboli into the following groups: amniotic fluid (4 publications), tumour (60 publications), fat (43 publications), cholesterol (19 publications), and intravascular debris (12 publications). We then summarized the available literature on each cause of NTES. CONCLUSIONS: NTES of tissue origin is an uncommon but important diagnosis to consider particularly in younger stroke patients and in certain clinical settings. Treatment for NTES is currently anecdotal and based on small case series. Embolectomy may emerge as the therapy of choice due to the longer treatment timeframe and heterogeneity of the emboli.

Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence.

BACKGROUND: Cytomegalovirus disease in patients with inflammatory bowel disease is frequently the result of viral reactivation. Conversely, primary CMV infection is believed to be uncommon in immunocompetent adults due to high population seroprevalence. OBJECTIVES: The aim of this study was to examine the frequency and severity of primary cytomegalovirus infection in an adult cohort of IBD patients. STUDY DESIGN: A retrospective review of a prospectively maintained database of 3200 IBD patients attending a single academic centre was performed. Patients with primary CMV infection 2010-13 were identified; clinical, serologic, and virologic parameters were studied in detail. The seroprevalence of CMV in the patient population was also evaluated. RESULTS: Eight patients with IBD (UC = 3, IBD-U = 1, CD = 4) presented with primary CMV infection. Patients presented with both gastrointestinal and extraintestinal symptoms. Mean age was 33 years, and median duration of disease was 72 months. All eight patients were receiving a thiopurine immunomodulator. Median duration of IM use was 144 weeks (range 7-720 weeks). All 8 patients required hospitalisation, with 1 ICU admission; the median length of hospital stay was 11 days (range 6-27). Infection resolved in all cases with withdrawal of immunomodulator and/or antiviral therapy. Seroprevalence of IgG to CMV, indicating prior exposure, in a subgroup of IBD patients (n = 80) was 30.5% and increased with age. CONCLUSION: Primary cytomegalovirus infection can cause a severe illness in IBD patients, particularly those receiving immunosuppression. In areas where adult CMV seroprevalence is low, evidence of CMV should be sought in IBD patients presenting with any febrile systemic illness.

A Systematic Review of the Causes and Management of Ischaemic Stroke Caused by Nontissue Emboli.

INTRODUCTION: The inadvertent or purposeful introduction of foreign bodies or substances can lead to cerebral infarction if they embolize to the brain. Individual reports of these events are uncommon but may increase with the increased occurrences of their risk factors, for example, intra-arterial procedures. METHOD: We searched EMBASE and MEDLINE for articles on embolic stroke of nontissue origin. 1889 articles were identified and screened and 216 articles were ultimately reviewed in full text and included in qualitative analysis. Articles deemed relevant were assessed by a second reviewer to confirm compatibility with the inclusion criteria. References of included articles were reviewed for relevant publications. We categorized the pathology of the emboli into the following groups: air embolism (141 reports), other arterial gas embolisms (49 reports), missiles and foreign bodies (16 reports), and others, including drug embolism, cotton wool, and vascular sclerosant agents. CONCLUSION: Air and gaseous embolism are becoming more common with increased use of interventional medical procedures and increased popularity of sports such as diving. There is increasing evidence for the use of hyperbaric oxygen for such events. Causes of solid emboli are diverse. More commonly reported causes include bullets, missiles, and substances used in medical procedures.

Gender dysphoria - prevalence and co-morbidities in an irish adult population.

INTRODUCTION: Gender dysphoria (GD) is a condition in which there is a marked incongruence between an individual's psychological perception of his/her sex and their biological phenotype. Gender identity disorder was officially renamed "gender dysphoria" in the DSM-V in 2013. The prevalence and demographics of GD vary according to geographical location and has not been well-documented in Ireland. METHODS: We retrospectively reviewed medical records of 218 patients with suspected or confirmed GD referred to our endocrine service for consideration of hormonal therapy (HT) between 2005 and early 2014. We documented their demographics, clinical characteristics, and treatment during the study period. RESULTS: The prevalence of GD in the Irish population was 1:10,154 male-to-female (MTF) and 1:27,668 female-to-male (FTM), similar to reported figures in Western Europe. 159 of the patients were MTF and 59 were FTM, accounting for 72.9% and 27.1% of the cohort, respectively. The rate of referral has increased year-on-year, with 55 patients referred in 2013 versus 6 in 2005. Mean ages were 32.6 years (MTF) and 32.2 years (FTM). 22 of the patients were married and 41 had children, with 2 others having pregnant partners. 37.6% were referred by a psychologist, with the remainder evenly divided between GPs and psychiatric services. There were low rates of coexistent medical illness although psychiatric conditions were more prevalent, depression being a factor in 34.4% of patients. 5.9% of patients did not attend a mental health professional. 74.3% are currently on HT, and 9.17% have had gender reassignment surgery (GRS). Regret following hormonal or surgical treatment was in line with other Western European countries (1.83%). CONCLUSION: The incidence of diagnosis and referral of GD in Ireland is increasing. This brings with it multiple social, health, and financial implications. Clear and accessible treatment pathways supported by mental health professionals is essential.