Histologic Remission (NANCY Index) is Superior to Endoscopic Mucosal Healing in Predicting Relapse Free Survival in Patients With Ulcerative Colitis in Clinical and Endoscopic Remission.

BACKGROUND: Histologic activity is recognized as an important predictor of relapse in ulcerative colitis (UC) patients. Current treatment targets aim at mucosal healing; however, many patients continue to have histologic activity. GOALS: The aim was to assess histologic activity using the validated Nancy histologic index (NHI) score as a predictor of future relapse amongst UC patients in endoscopic and clinical remission. STUDY: In this retrospective cohort study, UC patients in clinical and endoscopic remission at a single tertiary center between 2015 and 2018, who underwent a surveillance colonoscopy were included. Clinical remission was defined by partial Mayo score (MSp) <2, and endoscopic remission was defined by Mayo endoscopic subscore (MES) ≤1. Histologic remission was defined by NHI <2. Predictive factors associated with the primary endpoint of clinical relapse were analyzed. RESULTS: A total of 74 of 184 UC patients were included in the study. Amongst this cohort, 33 patients (45%) demonstrated histologic activity (NHI >1) at enrollment. The median follow-up time was 42 months (interquartile range: 26 to 63 mo) with median relapse free period of 30 months (interquartile range: 18 to 48 mo). Kaplan-Meier analysis demonstrated patients with MES 0 ( P =0.02) and histologic remission ( P <0.0001) had significantly longer relapse free survival. On multivariate analysis only histologic activity remained an independent risk factor of future clinical relapse (hazard ratio: 4.36, confidence interval: 1.68-11.27, P =0.002). CONCLUSION: Histologic remission using the NHI independently predicts significantly longer relapse free survival and may be a superior therapeutic target than endoscopic remission.

Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease.

Importance: Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). Objective: To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). Design, Setting, and Participants: Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients. Exposures: Genetic variants associated with TIM. Main Outcomes and Measures: Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 × 109/L or less or a decline in absolute neutrophil cell count to 1.0 × 109/L or less leading to a dose reduction or drug withdrawal. Results: Among 1077 patients (398 affected and 679 unaffected; median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years]; 540 [50%] women; 602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients; odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 × 10-9). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients; OR, 38.2 [95% CI, 5.1 to 286.1], P = 1.3 × 10-8), which was replicated in a different cohort (2.7% [2/73] affected vs 0.2% [2/840] unaffected patients; OR, 11.8 [95% CI, 1.6 to 85.0], P = .03). Carriage of any of 3 coding NUDT15 variants was associated with an increased risk (OR, 27.3 [95% CI, 9.3 to 116.7], P = 1.1 × 10-7) of TIM, independent of TPMT genotype and thiopurine dose. Conclusions and Relevance: Among patients of European ancestry with IBD, variants in NUDT15 were associated with increased risk of TIM. These findings suggest that NUDT15 genotyping may be considered prior to initiation of thiopurine therapy; however, further study including additional validation in independent cohorts is required.

Paradoxical psoriasiform reactions of anti-tumour necrosis factor therapy in inflammatory bowel disease patients.

Anti-tumour necrosis factor (TNF) agents have demonstrated efficacy in inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis or psoriasiform-like reactions are among the most common adverse reactions. We retrospectively identified cases of anti-TNF-induced psoriasis or psoriasiform manifestations in IBD patients at a tertiary centre in Australia. A total of 10 (six females) of 270 (3.7%) IBD patients treated with anti-TNF therapy developed drug-induced psoriatic or psoriasiform-like reactions: five patients were treated with infliximab and five with adalimumab; nine had Crohn disease. The time from initiation of anti-TNF agent to onset of rash was 7.5 months on average. The most frequent distributions were the scalp (7/10) and extremities (6/10). Three patients discontinued anti-TNF treatment with resolution of the rash. Topical treatment of the lesions allowed continued use of biological agent in the majority. Paradoxical psoriatic lesions are recognised adverse events associated with anti-TNF therapy, but discontinuation of therapy due to dermatological complications is required only rarely, even in patients with psoriasiform lesions.

Psychometric Properties of the Malay Version of the Dutch Eating Behaviour Questionnaire (DEBQ) in a Sample of Malaysian Adults Attending a Health Care Facility.

OBJECTIVE: This study aims to investigate the psychometric properties of the Malay version of the Dutch Eating Behaviour Questionnaire (DEBQ) among Malaysian adults. METHOD: The Malay version of the DEBQ instrument was administered to 398 outpatients (269 women and 129 men) at the University of Malaya Medical Centre (UMMC). Confirmatory Factor Analysis (CFA) was conducted to study the construct validity of the instrument. Composite reliability coefficient, Raykov's rho, was used to determine the internal consistency. RESULTS: The proposed three-factor structure for the DEBQ instrument was appropriate, although three items (Items 21, 14 and 27) showed problematic loadings with inappropriate model fit and were removed. The modified version had an appropriate model fit χ2/df = 2.129, TLI = 0.908, CFI = 0.918, RMSEA = 0.053 (90%CI = 0.048-0.058), close-fit P-value = 0.136 and satisfactory internal consistency of 0.914 for emotional eating scale, 0.819 for external eating scale and 0.856 for restrained eating scale. DISCUSSION: The Malay version of the DEBQ is a valid instrument to study eating behaviour traits among Malaysian adults. Further research is warranted to determine if Items 14 and 27 are appropriate for the Malaysian population.

Red blood cell transfusion is associated with further bleeding and fresh-frozen plasma with mortality in nonvariceal upper gastrointestinal bleeding.

BACKGROUND: Blood products are commonly transfused for patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). While concerns exist about further bleeding and mortality in subsets of patients receiving red blood cell (RBC) transfusion, the impact of non-RBC blood products has not previously been systematically investigated. The aim of the study was to investigate the associations between blood products transfusion, further bleeding, and mortality after acute NVUGIB. STUDY DESIGN AND METHODS: A retrospective cohort study examined further bleeding and 30-day and 1-year mortality in adult patients who underwent gastroscopy for suspected acute NVUGIB between 2008 and 2010 in three tertiary hospitals in Western Australia. Survival analysis was performed. RESULTS: A total of 2228 adults (63% male) with 2360 hospital admissions for NVUGIB met the inclusion criteria. Median age at presentation was 70 years (range, 19-99 years). Thirty-day mortality was 4.9% and 1-year mortality was 13.9%. Transfusion of 4 or more units of RBCs was associated with greater than 10 times the odds of further bleeding in patients with a hemoglobin level of more than 90 g/L (odds ratio, 11.9; 95% confidence interval [CI], 3.1-45.7; p ≤ 0.001), but was not associated with mortality. Administration of 5 or more units of fresh-frozen plasma (FFP) was associated with increased 30-day (hazard ratio, 2.8; 95% CI, 1.3-5.9; p = 0.008) and 1-year (hazard ratio, 2.6; 95% CI, 1.3-5.0; p = 0.005) mortality after adjusting for coagulopathy, comorbidity, Rockall score, and other covariates. CONCLUSION: In this large, multicenter study of NVUGIB, RBC transfusion was associated with further bleeding but not mortality, while FFP transfusion was associated with increased mortality in a subset of patients.

Lymphoma and other lymphoproliferative disorders in inflammatory bowel disease: a review.

The lymphoproliferative disorders (LDs) are a heterogeneous group of at least 70 conditions that result from the clonal proliferation of B, T, and NK cells. Inflammatory bowel disease (IBD)-associated lymphomas are typically B-cell LD, while T-cell or Hodgkin's lymphomas are rare. In IBD patients not on immunosuppression, the risk of LD seems to be similar or slightly higher than the background population risk. Thiopurine therapy is associated with an increased risk: the relative risk is increased four- to sixfold and the absolute risk varies between 1 in 4000-5000 for those aged 20-29 to 1 in 300-400 in those over 70. It is difficult to quantify the risk of anti- tumor necrosis factor (TNF) therapy alone; however, it appears to be less than for thiopurines alone. There is particular concern regarding the development of post-transplant-like LD in those with latent epstein-barr virus (EBV) infection exposed to immunosuppressives, the occurrence of hepatosplenic T cell lymphoma in patients treated with combination anti-TNF and thiopurine therapy, and the development of hemophagocytic lymphohistiocytosis in those who acquire a primary EBV or other infections while on immunosuppressive medication. There are currently no guidelines for monitoring EBV (or other virus) status in patients on immunosuppression, although it could be used to monitor those who have a prior history of lymphoma and are about to start a thiopurine or anti-TNF agent. In discussing the risks of lymphoproliferative disorders associated with agents used for the treatment of IBD, patients can often be reassured that the benefits of such therapy still outweigh the small, but real, risks.

Knowledge and attitudes towards the use of histological assessments in ulcerative colitis by gastroenterologists vs pathologists.

BACKGROUND: Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis (UC). However, the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown. AIM: To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists. METHODS: A prospective, cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted. The survey consisted of 34 questions to assess gastroenterologists' and pathologists' knowledge (score out of 19) and attitudes towards histological assessment in UC. Survey questions were formulated using the European Crohn's and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines. It included knowledge of histological assessment of disease activity and dysplasia, knowledge of histological scoring systems for ulcerative colitis, uptake of histology scoring systems in routine practice, attitudes towards the role of histological activity, and the use of histological activity in clinical scenarios. RESULTS: Of 89 responders (77 gastroenterologists, 12 pathologists), there was almost universal acceptance that histological assessment should form part of UC evaluation [95% gastroenterologists, 92% pathologists]. However, gastroenterologists reported that 92% of their pathologists do not use a histological scoring system. Utilisation of a formal histological scoring system was preferred by 77% of gastroenterologists and 58% of pathologists. Both groups lacked awareness of the Geboes Score, Nancy Index and Robarts Histopathological Index scoring systems with 91%, 87%, and 92% of gastroenterologists respectively; and 83%, 83%, and 92% pathologists respectively, being uncertain of scoring systems' remission definitions. Histology knowledge score was not significantly different between gastroenterologists and pathologists [9/19 (IQR: 8-11) vs 8/19 (IQR: 7-10), P = 0.54]. Higher knowledge scores were predicted by hospital attending gastroenterologists (P = 0.004), participation in inflammatory bowel disease (IBD) multidisciplinary teams (P = 0.009), and self-declared IBD sub-specialist (P = 0.03). CONCLUSION: Histological remission is a recognised target for both gastroenterologists and pathologists. Despite this, knowledge of histological scoring systems and their utilisation is poor.

A comprehensive review of analyzing the chest X-ray images to detect COVID-19 infections using deep learning techniques.

COVID-19, a highly infectious respiratory disease a used by SARS virus, has killed millions of people across many countries. To enhance quick and accurate diagnosis of COVID-19, chest X-ray (CXR) imaging methods were commonly utilized. Identifying the infection manually by radio imaging, on the other hand, was considered, extremely difficult due to the time commitment and significant risk of human error. Emerging artificial intelligence (AI) techniques promised exploration in the development of precise and as well as automated COVID-19 detection tools. Convolution neural networks (CNN), a well performing deep learning strategy tends to gain substantial favors among AI approaches for COVID-19 classification. The preprints and published studies to diagnose COVID-19 with CXR pictures using CNN and other deep learning methodologies are reviewed and critically assessed in this research. This study focused on the methodology, algorithms, and preprocessing techniques used in various deep learning architectures, as well as datasets and performance studies of several deep learning architectures used in prediction and diagnosis. Our research concludes with a list of future research directions in COVID-19 imaging categorization.

BMI is important in predicting the loss of response in inflammatory bowel disease patients on tumour necrosis factor-α inhibitors.

INTRODUCTION: Obesity is an emerging phenomenon among patients with inflammatory bowel disease (IBD). This study aims to evaluate whether the response to tumour necrosis factor-α (TNF-α) inhibitors (infliximab and adalimumab) could be influenced by BMI in IBD. METHODS: We identified a cohort of 181 IBD patients attending a single-tertiary centre, naive to biologic therapy and stratified them according to their BMI. The primary outcome is the first occurrence of loss of response (LOR). RESULTS: The median BMI was 26 kg/m2 (15-63 kg/m2). Approximately 68% of patients had LOR on both adalimumab (ADA) (n = 52) and infliximab (IFX) (n = 71). However, 83% on ADA with BMI ≥30 kg/m2 had LOR compared to 61% on IFX with BMI ≥30 kg/m2. For patients on ADA, Cox regression analysis revealed that after accounting for age, sex, disease type, duration of disease, fistulising disease, smoking status, haemoglobin, C-reactive protein, albumin and platelet levels, there were statistically significant associations between BMI (≥30 kg/m2 vs. <30 kg/m2) and LOR [P = 0.010; hazard ratio (HR) 3.2; confidence interval (CI), 1.3-7.6]. However, for patients on IFX, after accounting for the same factors, the only significant factor was the association of lower rate of LOR with higher albumin levels (P = 0.024; HR 0.95; CI, 0.91-0.99). There was an increased accelerated time to LOR for patients on ADA with BMI ≥30 kg/m2 compared to BMI <30 kg/m2 (P = 0.026). However, there was no difference in time to LOR for patients on IFX (P = 0.177). CONCLUSION: BMI is important in predicting the LOR among IBD patients on TNF-α inhibitors, especially among patients receiving ADA.

Vedolizumab treatment persistence and safety in a 2-year data analysis of an extended access programme.

BACKGROUND: Vedolizumab was shown to be effective and safe for patients with ulcerative colitis (UC) or Crohn's disease (CD) in the GEMINI phase 3 and long-term safety (LTS) studies. AIM: To report treatment persistence and safety results up to 2 years after enrolment in the vedolizumab extended access programme (XAP) METHODS: Vedolizumab XAP is a phase 3b/4, prospective, open-label, multinational, interventional study. At rollover from GEMINI LTS, patients who were experiencing continued clinical benefit with vedolizumab received reduced dosing frequency from every 4 weeks (Q4W) to every 8 weeks (Q8W). Patient persistence on Q8W dosing, incidence of relapse, and safety 2 years after enrolment were investigated. RESULTS: We enrolled 311 patients (142 UC and 169 CD). At baseline, 93.7% (UC) and 89.3% (CD) of patients were in clinical remission; 93.0% (UC) and 84.6% (CD) reduced dosing frequency to Q8W at enrolment. Of those who reduced dosing frequency to Q8W at enrolment, 93.9% (UC) and 91.6% (CD) remained on Q8W dosing; 6.1% (UC) and 8.4% (CD) re-escalated to Q4W dosing. Relapse was reported in 9.1% (UC) and 14.0% (CD) of patients who reduced dosing to Q8W. Adverse events related to vedolizumab were infrequent; no new events were reported. CONCLUSION: We observed high patient persistence on vedolizumab Q8W in the first 2 years after the reduction of dosing frequency in the XAP along with low rates of Q4W dose re-escalation and relapse. The safety profile was consistent with previous reports. ClinicalTrials.gov: NCT02743806.

Self-management using crude herbs and the health-related quality of life among adult patients with hypertension living in a suburban setting of Malaysia.

PURPOSE: To determine the prevalence of crude herbs' use in the self-management of hypertension and the health-related quality of life (HRQOL) in patients with hypertension. METHODS: This cross-sectional study was performed among patients with hypertension attending a government health clinic. Socio-demographic characteristics, lifestyle modifications, medical history and predictors of crude herbs users were obtained. The diversity of crude herbs used was assessed using a modified international complementary and alternative medicine questionnaire (I-CAM-Q) and the HRQOL was assessed using the SF36 instrument. RESULTS: Out of the 294 patients recruited, 52.4% were female, 41.5% were Malay and 38.8% were within the 60 to69 age category. The prevalence of crude herbs users was 30.6% and the most common herbs used were pegaga (Centella asiatica), peria (Momordica charantia) and betik (Carica papaya). Using the regression analysis, significantly higher odds of using crude herbs are noted among Malay or Indian patients who have these characteristics: attained secondary education, experienced falls or muscle pain, and had systolic blood pressure of more than 140 mmHg. There was no significant difference in HRQOL domains between the crude herb users and non-users (p>0.05). CONCLUSION: Besides taking allopathic medications, certain patients with hypertension use crude herbs as a form of self-management. Although patients are adamant about integrating crude herbs as a form of self-management, the effects of doing so have not been properly investigated. This implies that the healthcare staff members need to communicate with the patients regarding the use of crude herbs together with conventional drugs.

Adherence to the Malaysian clinical practice guideline for depression by general practitioners in private practice in Penang.

INTRODUCTION: Most primary care in Malaysia is provided by general practitioners in private practice. To date, little is known about how Malaysian General Practitioners (GPs) manage patients with depression. We surveyed privately practising primary care physicians in the state of Penang, Malaysia, in relation to their experience of the Malaysian Clinical Practice Guideline (CPG) in Major Depressive Disorder, their current practice and perceived barriers in managing depression effectively. MATERIAL AND METHODS: A questionnaire based on the study aims and previous literature was developed by the authors and mailed to all currently registered GPs in private clinics in Penang. Survey responses were analysed using SSPS version 21. RESULTS: From a total of 386 questionnaires distributed, 112 (29%) were returned. Half of the respondents were unaware of the existence of any CPG for depression. One quarter reported not managing depression at all, while one third used anxiolytic monotherapy in moderate-severe depression. Almost 75 % of respondents reported making referrals to specialist psychiatric services for moderate-severe depression. Time constraints, patient non-adherence and a lack of depression management skills were perceived as the main barriers to depression care. CONCLUSIONS: Our findings highlight the need to engage privately practising primary care physicians in Malaysia to improve their skills in the management of depression. Future revisions of the Malaysian Depression CPG should directly involve more GPs from private practices at the planning, development and implementation stages, in order to increase its impact.

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

BACKGROUND: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling. METHODS: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression. RESULTS: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided. CONCLUSIONS: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.

The significance of ANCA positivity in patients with inflammatory bowel disease.

Traditionally anti-neutrophil cytoplasmic antibodies (ANCA) are used to subtype patients with inflammatory bowel disease (IBD) and to predict primary sclerosing cholangitis (PSC). The clinical utility of this testing in the Australian context is not known. Our retrospective, cross-sectional study looked at the results of ANCA testing performed during routine clinical review and aimed to retrospectively review (1) the distribution of different ANCA subtypes for IBD patients, (2) the temporal change of ANCA status, and (3) the predictive value of ANCA for PSC. Sixty-four IBD patients attending our hospital gastroenterology clinic between 2012 and 2016 had at least one ANCA test requested. Surprisingly, >80% of the IBD patients in our cohort who underwent ANCA testing had a positive ANCA result and a significant proportion had positive PR3 antibodies. However, no specific ANCA pattern predicted a specific IBD subtype or clinical course. Pairing ANCA and anti-Saccharomyces cerevisiae (ASCA) did not add value in subtyping IBD for these patients. Our study suggests that there is little value in ordering an ANCA for patients with IBD.

Micropulse Transscleral Cyclophotocoagulation in Keratoplasty Eyes.

PURPOSE: To assess the outcomes of micropulse transscleral cyclophotocoagulation for intraocular pressure (IOP) control in keratoplasty eyes. METHODS: Outcomes of micropulse laser treatments of postkeratoplasty eyes were retrospectively reviewed. IOP was assessed with applanation tonometry. Keratoplasty survival was calculated with Kaplan-Meier survival analysis. RESULTS: Sixty-one eyes in 57 patients received laser treatment; 31 eyes received 1, 21 received 2, 8 received 3, and 1 received 4 treatments. The median follow-up was 21 months (range, 2-35 months). At baseline, the mean IOP was 28 ± 11 mm Hg. At 1, 3, 6, and 12 months after the last treatment, respectively, the numbers of eyes with IOP data were 58, 50, 46, and 38; the mean IOP was 17 ± 7, 17 ± 8, 18 ± 9, and 15 ± 5 mm Hg; the proportions of eyes with IOP ≤ 15 mm Hg were 40%, 51%, 48%, and 55%; and the proportions with IOP ≤ 12 mm Hg were 21%, 29%, 20% and 29%. Six eyes (10%) received subsequent glaucoma filtration surgery. The mean number of antiglaucoma medications used before the initial treatment was 2.7 (range, 0-4) versus 2.2 (range, 0-4) at last follow-up. At baseline, 7 grafts were decompensated and 5 of 54 clear grafts (9%) had endothelial cell density < 700 cells/mm. Graft survival was 94% at 1 year and 81% at 2 years after the initial laser treatment. CONCLUSIONS: Micropulse transscleral cyclophotocoagulation is a noninvasive alternative to glaucoma filtration surgery for IOP reduction in keratoplasty eyes.

Post-colonoscopy colorectal cancers identified by probabilistic and deterministic linkage: results in an Australian prospective cohort.

OBJECTIVE: Post-colonoscopy colorectal cancers (PCCRCs) are recognised as a critical quality indicator. Benchmarking of PCCRC rate has been hampered by the strong influence of different definitions and methodologies. We adopted a rigorous methodology with high-detail individual data to determine PCCRC rates in a prospective cohort representing a single jurisdiction. SETTING: We performed a cohort study of individuals who underwent colonoscopy between 2001 and 2008 at a single centre serving Australian Capital Territory (ACT) and enclaving New South Wales (NSW) region. These individuals were linked to subsequent colorectal cancer (CRC) diagnosis, within 5 years of a negative colonoscopy, through regional cancer registries and hospital records using probabilistic and deterministic record linkage. All cases were verified by pathology review. Predictors of PCCRCs were extracted. PARTICIPANTS: 7818 individuals had a colonoscopy in the cohort. Linkage to cancer registries detected 384 and 98 CRCs for notification dates of 2001-2013 (ACT) and 2001-2010 (NSW). A further 55 CRCs were identified from a search of electronic medical records using International Classification of Diseases-10 diagnosis codes. After verification and exclusions, 385/537 CRCs (58% male) were included. PRIMARY OUTCOME MEASURE: PCCRC rates. RESULTS: There were 15 PCCRCs in our cohort. The PCCRC incidence rate was 0.384/1000 person-years and the 5-year PCCRC risk was estimated as 0.192% (95% CI 0.095 to 0.289). The index colonoscopy prior to PCCRC was more likely to show diverticulosis (p=0.017 for association, OR 3.56, p=0.014) and have poor bowel preparation (p=0.017 for association, OR 4.19, p=0.009). CONCLUSION: In this population-based cohort study, the PCCRC incidence rate was 0.384/1000 person-years and the 5-year PCCRC risk was 0.192%. These data show the 'real world' accuracy of colonoscopy for CRC exclusion.

Degos' disease with delayed involvement of the gastrointestinal tract.

A 75-year-old woman presented with pink papules over the trunk and limbs. Over the next few weeks, the papules became umbilicated and then developed into porcelain-white lesions with a rose or violaceous rim. A biopsy of one of these lesions revealed superficial and deep dermal lymphohistiocytic inflammation, mainly perivascular with a central zone of infarction consistent with Degos' disease. Three years later, she presented with increasing abdominal pain, anaemia, raised inflammatory markers and an abdominal bruit. Angiography showed splanchnic vessel stenosis possibly secondary to vasculitis and she underwent successful balloon dilatation. Treatment with prednisolone was commenced. There has been no recurrence of lesions in the 12 months since the balloon dilatation.

Induction of MMP-1, MMP-3 and TIMP-1 in normal dermal fibroblasts by chronic venous leg ulcer wound fluid*.

In the wound bed of chronic venous leg ulcers, an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may cause excessive proteolysis and impair wound granulation. Soluble mediators in the wound environment may be responsible for this imbalance. The in vitro effect of wound fluid from venous leg ulcers on dermal fibroblast production of MMP-1, MMP-3 and TIMP-1 was compared with the effect of acute wound fluid from two different sources: fluid from post-mastectomy axillary drains and fluid from skin graft donor sites. Significantly higher MMP-1 and MMP-3 levels were induced by chronic venous leg ulcer wound fluid compared with both types of acute wound fluid (P < 0.005). Chronic venous ulcer wound fluid reduced TIMP-1 protein levels significantly more than acute graft fluid (P < 0.05). Venous ulcer wound fluid significantly increased MMP-1 and MMP-3 production in dermal fibroblasts and reduced TIMP-1 production, confirming that mediators in the leg ulcer microenvironment can potentially induce excessive proteolysis in the ulcer dermis by altering the balance between MMPs and TIMPs. Inflammatory mediators including interleukin-1beta and tumour necrosis factor-alpha can induce these MMPs. Further work is required to confirm the factors responsible for the induction of a high MMP and low TIMP profile in fibroblasts by venous ulcer wound fluid.

Test anxiety: state, trait and relationship with exam satisfaction.

Test anxiety is defined as the reaction to stimuli that is associated with an individual's experience of testing or evaluating situations. This study aims to examine the fluctuation pattern of anxiety symptoms during a clinical examination and its relationship with underlying anxiety traits. Fourth year medical students of Penang Medical College undertaking the Ophthalmology clinical examination participated in this study. First phase of the survey, on anxiety symptoms was conducted immediately after the Ophthalmology clinical examination while the second phase, on pre-existing anxiety traits was conducted six weeks later with the aid of STAI instrument. Responses for both stages were combined and analyzed. Sixty-three of 122 students responded to both phases of the study, giving a response rate of 52%. All symptoms except trembling peaked 10 minutes before the exam begun showing a downward progression with no resurgence thereafter. Students with pre-existing anxiety traits had high anxiety scores 10 minutes into the examination and while with the examiners. Anticipatory anxiety is a source of concern and can effect performance and appropriate steps should be taken to help the students with this. A few other studies should be done to conclude.

Eating Behaviour Predicts Weight Loss Six Months after Bariatric Surgery: A Longitudinal Study.

Bariatric surgery is currently the most durable weight loss solution for patients with morbid obesity. The extent of weight loss achieved, however, is subject to variation due to various factors, including patients' behaviour. In this study, we aimed to identify pre- and post-surgical predictors of weight loss following bariatric surgery. This prospective study included 57 participants who went through bariatric surgery (laparoscopic Roux-en-Y gastric bypass: n = 30; laparoscopic sleeve gastrectomy: n = 23; one anastomosis gastric bypass-mini gastric bypass: n = 4) in two tertiary referral hospitals. Consenting participants were assessed prior to surgery (T0), and three months (T1) and six months (T2) after surgery. The assessment included interview and anthropometric measurements. The interview was done with the aid of instruments, including the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression screening and the Dutch Eating Behaviour Questionnaire (DEBQ) for eating behaviour assessment. Baseline comorbidity status was obtained from medical records. A Generalised Estimating Equation (GEE) was developed to determine predictors of weight loss. Participants in the study were mostly women (n = 37, 65%) with a mean age of 39.4 (SD = 10.01) years. The mean excess BMI loss (EBMIL) and total weight loss (TWL) at the sixth month was 63.31% and 23.83%, respectively. Anxiety, depression, and external eating scores reduced over time. Advancing age, high BMI, and higher scores for emotional and external eating emerged as significant negative predictors for TWL%. It can be concluded that the patients experienced substantial weight loss after surgery. Continuous monitoring of psychological well-being and eating behaviour are essential for optimal weight loss.