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Background Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated. Aims To investigate incidence and prevalence of Crohn's disease and ulcerative colitis and risk of colorectal cancer and all-cause mortality in these diseases. Methods Inflammatory bowel disease cases between 2000 and 2018 were identified from a national primary care database. Inflammatory bowel disease prevalence was forecast until 2025. The association between inflammatory bowel disease and colorectal cancer and all-cause mortality was investigated using age/sex-matched retrospective cohort studies. Hazard ratios were adjusted for age, sex, deprivation, comorbidity, smoking status and body mass index. Results Ulcerative colitis prevalence increased from 390 to 570 per 100 000 population from 2000 to 2017. Prevalence of Crohn's disease increased from 220 to 400 per 100 000. In 2017 male Crohn's disease prevalence was 0.35% (95% confidence interval 0.34-0.36); female prevalence was 0.44% (0.43-0.45). Prevalence of inflammatory bowel disease is predicted to be 1.1% by 2025. Incidence of ulcerative colitis and Crohn's disease was 23.2 (22.8-23.6) and 14.3 (14.0-14.7) per 100 000 person-years respectively. Subjects with ulcerative colitis were more likely to develop colorectal cancer than controls (adjusted Hazard Ratio 1.40 [1.23-1.59]). Colorectal cancer rates remained stable in inflammatory bowel diseases over time. Ulcerative colitis and Crohn's disease were associated with increased risk of all-cause mortality (1.17 [1.14-1.21] and 1.42 [1.36-1.48] respectively). Conclusions The UK prevalence of inflammatory bowel disease is greater than previous reports suggest and we predict an 11% increase in prevalence by the year 2025. Mortality risk in inflammatory bowel disease and colorectal cancer risk in ulcerative colitis are increased compared to matched controls.

Background Microcystic adnexal carcinoma (MAC) is a rare, locally invasive skin neoplasm most commonly in the head and neck. MAC is routinely treated surgically and scant data is available regarding the role of definitive chemoradiotherapy (chemoRT) as a surgical alternative. Methods A single case of MAC treated with upfront chemoRT is presented along with a review of the literature. Results A 73-year old man with locally advanced MAC of the philtrum and nose declined surgery and was treated with concurrent intensity-modulated RT (70Gy) and paclitaxel/carboplatin. His tumor responded clinically within two weeks of treatment. Partial radiographic response was observed at three months with improvement up to one year post-treatment. He remains asymptomatic and progression-free six years from the completion of his treatment. Conclusion Definitive chemoRT may be a nonsurgical treatment alternative for MAC when surgery is not possible or declined.

Summary Background Childhood maltreatment is a global public health, human rights, and moral issue that is associated with a substantial mental health burden. We aimed to assess the association between childhood maltreatment and the development of mental ill health and the initiation of new prescriptions for mental ill health. Methods In this population-based, retrospective, open cohort study, we used a dataset from individuals in The Health Improvement Network (THIN) database. THIN database comprises UK electronic medical records taken from 787 general practices throughout the UK. We used read codes in these records to identify exposed patients (those with a read code identifying officially confirmed childhood maltreatment or a maltreatment-related concern) and up to two unexposed patients (those without such read codes) from the same general practice, who were matched by age and sex. We evaluated the risk of developing depression, anxiety, or serious mental illness (a composite mental ill health outcome) or initiation of a prescription drug used to treat mental ill health, and the odds ratio of these events at baseline, in the exposed versus unexposed patients. Findings The first possible date for cohort entry (the study start date) was Jan 1, 1995, and patients could enter the cohort until the study end date, Dec 31, 2018. During the study period, 11 831 850 patients were eligible to participate. Of these patients, we identified 217 758 (1·8%) patients with any recorded childhood maltreatment. These patients were matched to 423 410 unexposed control patients with no recorded exposure to childhood maltreatment. The exposed group were followed up for a median of 1·8 years (IQR 0·6–4·3) versus 3·2 years (1·3–6·1) in the unexposed group. During the study period, 11 665 (5·9%) new diagnoses of mental ill health were made in the exposed group, giving an incidence rate of 16·8 events per 1000 person-years versus 15 301 (3·7%) new recorded diagnoses at an incidence rate of 8·3 events per 1000 person-years in the unexposed cohort, giving an adjusted IRR of 2·14 (95% CI 2·08–2·19). 30 911 (14·8%) patients in the exposed group received a new prescription for any type of mental ill health (incidence rate 46·5 events per 1000 person-years) versus 36 390 (8·9%) patients in the unexposed group (20·5 per 1000 person-years) resulting in an adjusted IRR of 2·44 (95% CI 2·40–2·48). Interpretation Childhood maltreatment is thought to affect one in three children globally; therefore, a doubled risk of developing mental ill health among these individuals represents a substantial contribution to the mental ill health burden in the UK. It is imperative that public health approaches, including those aimed at preventing and detecting childhood maltreatment and its associated negative consequences, are implemented to prevent mental ill health. Funding None.

Objective\ud To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.\ud \ud Methods\ud We performed a propensity score–matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.\ud \ud Results\ud During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score–matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62–1.10) and 0.79 (95% CI 0.57–1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75–1.27) and 0.85 (95% CI 0.61–1.20), respectively. There was no effect modification by age or sex.\ud \ud Conclusion\ud No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

In chronic infection, inflammation and cancer, the tissue microenvironment controls how local immune cells behave, with tissue-resident fibroblasts emerging as a key cell type in regulating activation or suppression of an immune response. Fibroblasts are heterogeneous cells, encompassing functionally distinct populations, the phenotypes of which differ according to their tissue of origin and type of inciting disease. Their immunological properties are also diverse, ranging from the maintenance of a potent inflammatory environment in chronic inflammation to promoting immunosuppression in malignancy, and encapsulating and incarcerating infectious agents within tissues. In this Review, we compare the mechanisms by which fibroblasts control local immune responses, as well as the factors regulating their inflammatory and suppressive profiles, in different tissues and pathological settings. This cross-disease perspective highlights the importance of tissue context in determining fibroblast–immune cell interactions, as well as potential therapeutic avenues to exploit this knowledge for the benefit of patients with chronic infection, inflammation and cancer. Fibroblasts are not just crucial structural cells; they exist as multiple functionally diverse populations, defined by their location and context, and regulate tissue immunity. Here, the authors review the immunological properties of fibroblasts, comprising both pro-inflammatory and immunosuppressive activities, in different tissues and disease states.

Background Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet’s syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM. Methods A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis. Results We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn’s disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86). Conclusions Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.

Notch signaling regulates squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is tumor suppressive. Here, we show that conditional activation of Notch in squamous cells activates a context-specific gene expression program through lineage-specific regulatory elements. Among direct Notch target genes are multiple DNA damage response genes, includingIER5, which we show is required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes.IER5is epistatic toPPP2R2A, a gene that encodes the PP2A B55α subunit, which we show interacts with IER5 in cells and in purified systems. Thus, Notch and DNA-damage response pathways converge in squamous cells on common genes that promote differentiation, which may serve to eliminate damaged cells from the proliferative pool. We further propose that crosstalk involving Notch and PP2A enables tuning and integration of Notch signaling with other pathways that regulate squamous differentiation.

Background With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records. Methods A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Individuals were classified according to BMI category and metabolic abnormalities (diabetes, hypertension and dyslipidaemia). Diagnosis of NAFLD during follow-up was the primary outcome measure. NAFLD was identified by Read codes. Results During a median follow-up period of 4.7 years, 12,867 (0.3%) incident cases of NAFLD were recorded in the cohort of 4,121,049 individuals. Compared to individuals with normal weight and no metabolic abnormalities, equivalent individuals who were overweight, or obese were at significantly greater risk of incident NAFLD (Adjusted HR 3.32 (95%CI 2.98–3.49), and 6.92 (6.40–7.48, respectively). Metabolic risk factors further increased risk, including in those with normal weight and 1 (2.27, 1.97–2.61) or = Conclusions MHO individuals are at greater risk of developing NAFLD compared to those with normal weight. This finding supports that the MHO phenotype is a temporary state, and weight must be considered a risk factor even before other risk factors develop. Being normal weight with metabolic abnormalities was also associated with risk of NAFLD.

Notch signaling regulates normal squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is a key tumor suppressive pathway. To identify the direct targets of Notch that produce these phenotypes, we introduced a conditional Notch transgene into squamous cell carcinoma cell lines, which respond to Notch activation in 2D culture and in organoid cultures by undergoing differentiation. RNA-seq and ChIP-seq analyses show that in squamous cells Notch activates a context-specific program of gene expression that depends on lineage-specific regulatory elements, most of which lie in long- range enhancers. Among the direct Notch target genes are multiple DNA damage response genes, includingIER5, which is regulated by Notch through several enhancer elements. We show thatIER5is required for Notch-induced differentiation in squamous carcinoma cells and in TERT-immortalized keratinocytes. Its function is epistatic toPPP2R2A, which encodes the B55αsubunit of PP2A, and IER5 interacts with B55αin cells and in purified systems. These results show that Notch and DNA-damage response pathways converge in squamous cells and that some components of these pathways promote differentiation, which may serve to eliminate DNA-damaged cells from the proliferative pool in squamous epithelia. Crosstalk involving Notch and PP2A may enable Notch signaling to be tuned and integrated with other pathways that regulate squamous differentiation. Our work also suggests that squamous cell carcinomas remain responsive to Notch signaling, providing a rationale for reactivation of Notch as a therapeutic strategy in these cancers.ImpactOur findings highlight context-specific crosstalk between Notch, DNA damage response genes, and PP2A, and provide a roadmap for understanding how Notch induces the differentiation of squamous cells.

BACKGROUND Perianal abscess [PA] is associated with inflammatory bowel disease [IBD]. The incidence of IBD after a diagnosis of PA and potential predictors of a future diagnosis of IBD are unknown. METHODS The Health Improvement Network [THIN] is a primary care database representative of the UK population. Incident cases of PA were identified between 1995 and 2017. Subjects with PA were matched to controls within the same general practice. The primary outcome was a subsequent diagnosis of Crohn's Disease [CD] or ulcerative colitis [UC]. A Cox regression model was used to assess potential predictors of a new diagnosis of CD or UC following PA. RESULTS The risk of CD was higher in the PA cohort compared with controls; adjusted hazard ratio [HR] 7.51 (95% confidence interval [CI] 4.86-11.62), p < 0.0001. The risk of UC was also higher in the PA cohort compared with controls; adjusted HR 2.03 [1.38-2.99], p < 0.0001. Anaemia in men (HR 2.82 [1.34-5.92], p = 0.002), and use of antidiarrhoeal medications (HR 2.70 [1.71-4.25], p < 0.0001) were associated with an increased risk of CD following PA. Anaemia in men (HR 2.58 [1.09-6.07], p = 0.03), diarrhoea (HR 2.18 [1.23-3.85], p = 0.007), and use of anti-diarrhoeal medication (HR 2.27 [1.19-4.30], p = 0.012) were associated with an increased risk of UC following PA. CONCLUSION Subjects with PA are at an increased risk of subsequent diagnosis of CD and UC. Clinicians should strongly consider investigation for IBD in young patients presenting with diarrhoea and anaemia [in males] following PA. Future research should discern appropriate screening strategies for this high-risk cohort.

This study presents results from an investigation into the effect of positive incentives on cycling behaviour among 1802 commuters in the Twente region of the Netherlands. The authors used an on-line survey, which included mock-up apps with incentives to commute to work by bicycle. They tested five reward schemes, namely social rewards (such as badges), in-kind gifts, money, competition, and cooperation. They used the survey data in a multinomial logit model to estimate to what extent travellers will use the app and increase their cycling frequency and which incentives they prefer. The model results show that respondents who sometimes cycle to work are more positive about incentive schemes than respondents who never cycle and that offering an app with in-kind gifts is probably most effective. Interestingly, non-cyclists are more likely to change their behaviour for a reward if they care about travel costs, while occasional cyclists are more likely to cycle more often in response to incentives if they care about attributes that are related to the cycling itself. This also depends on attitudes towards cycling and on socio-demographic variables.

BackgroundAchalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited.MethodsHospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality.ResultsThere were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), pConclusionThe incidence of achalasia is 1.99 per 100 000 population in secondary care data and 1.53 per 100 000 person-years in primary care data. Subjects with achalasia have an increased incidence of oesophageal cancer, aspiration pneumonia, lower respiratory tract infections and higher mortality. Clinicians treating patients with achalasia should be made aware of these associated morbidities and its increased mortality.

Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer. We evaluated the efficacy of everolimus in aggressive, radioactive iodine–refractory (RAIR) thyroid cancer and correlated tumor mutational profiling with response. Exploratory medullary and anaplastic thyroid cancer cohorts were included. Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009 to 2013 in patients with incurable RAIR thyroid cancer who had radiographic progression six months prior to enrollment. The primary endpoint was progression-free survival (PFS) with a median follow-up of 31.8 months. The study is closed to enrollment but treatment and follow-up are ongoing. A targeted next-generation sequencing platform was used for mutational analysis. Results: Thirty-three patients with differentiated thyroid cancer (DTC), 10 with medullary thyroid cancer (MTC), and 7 with anaplastic thyroid cancer (ATC) enrolled. For the DTC cohort, median PFS was 12.9 months (95% CI, 7.3–18.5) with a 2-year PFS of 23.6% (95% CI, 10.5–39.5). Median OS was not reached; 2-year OS was 73.5% (95% CI, 53.8–85.8). Among ATC patients, 1 had a partial response and was progression-free until 17.9 months after study entry and one had disease stability for 26 months, respectively. The genomically profiled cohort enriched for PI3K/mTOR/Akt alterations. PI3K/mTOR/Akt–mutated ATC subgroups appeared to benefit from everolimus. Treatment-related adverse events were as anticipated. Conclusions: Everolimus has significant antitumor activity in thyroid cancer. While genomic profiling does not currently guide therapeutic selection in thyroid cancer patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine. Clin Cancer Res; 24(7); 1546–53. ©2018 AACR.

Background and Aims: Transversus abdominis plane (TAP) block is a technique proposed to minimise pain after anterior iliac crest bone harvesting. This study aims to evaluate the postoperative pain in patients who receive ultrasound-guided TAP block to supplement routine wound infiltration. Material and Methods: A total of 143 patients aged between 6 and 22 years were randomised into two groups. Patients in group A received supplemental TAP block on the same side. Patients in group B received local anesthetic wound infiltration alone. Pain scores were compared at the first and 24th postoperative hours. Results: TAP block significantly reduced pain and delirium in the immediate postoperative period. The mean FLACC (Face, Legs, Activity, Cry, Consolability) score after 10 min was 0.8 in group A versus 1.8 in group B (P = 0.001). The mean Watcha scale at 10 min was 1.0 in group A versus 1.2 in group B (P = 0.001). After 24 h, 81.7% of patients in group A had no pain versus 59.7% in group B (P = 0.004). The incidence of intolerable pain at 24 h was 5.6% in group B versus 0% in group A (P = 0.04). Cumulative ambulation scores were significantly better in group A (P < 0.05). There was a strong and positive correlation between the analgesia and ability to ambulate comfortably at 24 h postop (Pearson's coefficient 0.95). Conclusion: Supplemental ultrasound-guided TAP block given intraoperatively reduces the postoperative pain. The incidence of emergence delirium was low. These patients were also able to ambulate earlier.

To assess the relationship between Intimate partner violence (IPV) (a highly prevalent form of domestic abuse) with the subsequent development of temporomandibular joint disorder (TMD).A retrospective open cohort study using a UK primary care database was undertaken. 18,547 women exposed to IPV were matched by age to 74,188 unexposed women. Defined through clinical codes the outcome of interest was TMD, and adjusted incidence rates (aIRR) were used to describe the relationship after considering covariates of interest.94 individuals in the exposed group were clinically coded with TMD during the study period translating to an incidence rate (IR) or 1.59 per 1000 person years. This was in comparison to 342 outcomes in the unexposed group (IR 1.21 per 1000 person years). The unadjusted IRR was 1.31 (95% CI 1.04-1.65; p 0.020) and after adjustment for important covariates increased to 1.45 (95% CI 1.14-1.84; p 0.002).Our results suggest that the development of TMD may be associated with exposure to IPV in women.In the first cohort to do so, we have identified a moderate association between Intimate partner violence exposure and subsequent development of TMD. This highlights an opportunity for screening of abuse in individuals presenting with TMD.

Cancer metabolism has emerged as one of the most interesting old ideas being revisited from a new perspective. In the early 20th century Otto Warburg declared metabolism the prime cause in a disease of many secondary causes, and this statement seems more prescient in view of modern expositions into the true nature of tumor evolution. As the complexity of tumor heterogeneity becomes more clear from a genetic perspective, it is important to consider the inevitably heterogeneous metabolic components of the tumor and the tumor microenvironment. High grade gliomas remain one of the most difficult to treat solid tumors, due in part to the highly vascularized nature of the tumor and the maintenance of more resistant stem-like subpopulations within the tumor. Maintenance of glioma stem cells (GSCs) requires specific alterations within the cells and the greater tumor microenvironment with regards to signaling and metabolism. Specific niches within gliomas help foster the survival of stem-like sub-populations of cells with high tumorigenicity and high metabolic plasticity. Understanding these maintenance pathways and the metabolic dependencies within the niche may highlight potential avenues of addressing tumor resistance and recurrence in glioma patients.

A 33-year-old man with ulcerative colitis presented with 5-day history of fever, night sweats, abdominal pain and increased stool frequency. He was on mesalazine M/R 1 g once daily, 6-mercaptopurine (6-MP) 75 mg once daily and prednisolone 40 mg once daily. Examination revealed fever and tachycardia. Blood examinations identified a persistent leucopenia, C reactive protein of 23 mg/L and an initial alanine transaminase of 855 IU/L. Flexible sigmoidoscopy revealed well-demarcated, punched-out ulcers in the proximal rectum and distal sigmoid, with histology pathognomonic of cytomegalovirus (CMV). CMV DNA PCR was 51 140 copies/mL. Despite prompt withdrawal of 6-MP, steroids and initiation of intravenous ganciclovir on day 2 of admission, his systemic illness, diarrhoea and fever persisted until day 19 of antiviral therapy. Other copathogens and lymphoma were ruled out on serology and CT scan, respectively. After an unusually prolonged course of antiviral therapy, the patient made a full clinical recovery, bloods normalised and there were two consecutive undetectable CMV DNA PCRs.

Objectives Pediatric eustachian tube dysfunction (ETD), otitis media with effusion (OME), and tympanic membrane retraction (TMR) have been well studied, but no large analyses have described the associated burden beyond childhood. The potential impact and feasibility of prospective trials designed to optimize management of affected adults are thus unclear. Our objectives were therefore (1) to determine the national visit burden associated with ETD/OME/TMR beyond childhood and (2) to examine risk factors specific to adults, highlighting differences in comparison with children. Study Design Cross-sectional analysis of a national database. Setting Ambulatory visits in the United States. Methods Epidemiologic analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (2005-2012) included data from 761,291 observations representing 9,369,388,092 visits. Chi-square test with Bonferroni adjustment for multiple comparisons was utilized for hypothesis testing. Results Visits related to ETD/OME/TMR exceeded 2 million per annum in patients 0 to 20 years of age (mean 2,625,965; range 2,239,288-3,329,858). Among those20 years old, visits also exceeded 2 million (mean, 2,025,050; range, 1,550,669-2,353,799). Characteristics differed according to age: whereas ETD/OME/TMR affected more males20 years, females were more frequently diagnosed in the older age group ( P.0001). Patients20 to 40 years of age were the most likely to visit the emergency department ( P = .0022). There were no statistically significant differences per season or region. The related diagnoses of cholesteatoma and chronic otitis media prompted additional visits. Conclusions ETD/OME/TMR is associated with a visit burden for adults that extends beyond childhood. Among adults, there may also be age-related differences in patient characteristics.

Background: Fresh frozen plasma (FFP) should be thawed before transfusing to the patient. Prolonged or uncontrolled thawing can denature plasma proteins. The potential risk of contamination by wet thawing had always been a point of concern. Aims: Here, we compared and evaluated the effect of thawing on clotting factor activities by two different methods (wet and dry) and other factors such as risk of bacterial contamination, throughput, turnaround time, and efficacy of thawing. Subjects and Methods: All FFPs were prepared from Group O donors and stored at −40°C. Twenty-one FFPs were thawed in Plasmatherm II at 45°C for 15 min and another 21 were thawed in thawing bath at 37°C for 20–30 min randomly. Analysis of prothrombin time, activated partial thromboplastin time, fibrinogen, and factor VIII was done in ACL TOP 300 (IL) at the time of preparation and immediately after thawing of FFPs. Volume, duration of thawing, ease of use, accessibility, and equipment maintenance were also compared. Results: There was a statistically significant difference in coagulation parameters after thawing in both methods compared to the time of preparation (P < 0.05), but all values were within normal limits. There was no significant difference in coagulation parameters between the two methods (P > 0.05). Mixed bacterial growth was observed from swabs taken from the water bath. Conclusion: Plasmatherm II can be a good alternative to water bath to rapidly thaw FFPs by preserving coagulation factors and eliminating the risk of bacterial contamination.

Background and Aims Patients with ulcerative colitis [UC] may present as emergencies and require rapid escalation of therapy. This study aimed to assess the mortality, colectomy, and readmission risks, during and following a first emergency admission with UC. Methods Using Hospital Episode Statistics, subjects aged between 18 and 60 years, coded with a first emergency admission with UC, were identified between 2007 and 2017. Influences of demographic factors, comorbidity, anti-tumour necrosis factor [TNF] therapy, and provider UC activity on mortality and colectomy were examined. Results A total of 10 051 subjects (46% female; median age 33 years [interquartile range [IQR] 25–44]) were identified. Mortality was 0.2% in hospital and 0.5% at 12 months and, following colectomy during acute admission, it was 1.4% in hospital and 2.1% at 12 months. Females had reduced risk of colectomy during admission: odds ratio [OR] 0.73 (95% confidence interval [CI] 0.62–0.85). Comparing the period 2007–2011 with 2012–2017, the rate of colectomy fell during acute admissions: OR 0.85 [0.72–0.99], p = 0.038 and at 12 months after admission: OR 0.73 [0.61–0.87]. Anti-TNF therapy increased 4-fold in acute UC admissions from 2007–2017. Those receiving anti-TNF therapy had a 70% increased risk of colectomy during index admission compared with those not receiving anti-TNF: OR 1.72 [1.29–2.31]. Increased time to colectomy during first admission was associated with female sex: hazard ratio [HR] 0.84 [0.72–0.98] and Asian ethnicity: HR 0.61 [0.44–0.85], whereas reduced time was associated with increased comorbidity, lower deprivation, and high provider volume of colectomies for UC: HR 1.59 [1.31–1.93]. Conclusions Mortality following colectomy was 1.4% in hospital and 2.1% at 12 months, and no significant change over time was observed. Colectomy during emergency admission for UC was less common in females. Rates of anti-TNF therapy during emergency admission for UC have increased and overall colectomy rates have fallen. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

BackgroundInternationally, intimate partner violence (IPV) cohorts have demonstrated associations with depression and anxiety. However, this association has not yet been described in a UK population, nor has the association with serious mental illness (SMI).AimsTo explore the relationship between IPV exposure and mental illness in a UK population.MethodWe designed a retrospective cohort study whereby we matched 18 547 women exposed to IPV to 74 188 unexposed women. Outcomes of interest (anxiety, depression and SMI) were identified through clinical codes.ResultsAt baseline, 9174 (49.5%) women in the exposed group had some form of mental illness compared with 17 768 (24.0%) in the unexposed group, described as an adjusted odds ratio of 2.62 (95% CI 2.52–2.72). Excluding those with mental illness at baseline, 1254 exposed women (incidence rate 46.62 per 1000 person-years) went on to present with any type of mental illness compared with 3119 unexposed women (incidence rate 14.93 per 1000 person-years), with an aIRR of 2.77 (95% CI 2.58–2.97). Anxiety (aIRR 1.99, 95% CI 1.80–2.20), depression (aIRR 3.05, 95% CI 2.81–3.31) and SMI (aIRR 3.08, 95% CI 2.19–4.32) were all associated with exposure to IPV.ConclusionsIPV remains a significant public health issue in the UK. We have demonstrated the significant recorded mental health burden associated with IPV in primary care, at both baseline and following exposure. Clinicians must be aware of this association to reduce mental illness diagnostic delay and improve management of psychological outcomes in this group of patients.

Aims Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the leading causes of liver transplantation in the West. This study seeks to examine whether women with gestational diabetes mellitus (GDM) are at increased risk of developing NAFLD compared to women without GDM. Methods We conducted a population-based retrospective matched-controlled cohort study utilising The Health Improvement Network (THIN), a large primary care database representative of the United Kingdom population, between 01/01/1990 to 31/05/2016 followed by systematic review of available literature. The study population included 9640 women with GDM and 31,296 controls without GDM, matched for age, body mass index (BMI) and time of pregnancy. All study participants were free from NAFLD diagnosis at study entry. Patients with GDM and patients developing NAFLD were identified by clinical codes. Results The median (range) follow-up duration was similar in women with and without GDM (2.95 (1.21–6.01) vs 2.85 (1.14–5.75) years respectively). Unadjusted incidence rate ratio (IRR) for NAFLD development in women with vs without GDM was 3.28 (95% CI 2.14–5.02), which remained significant after adjustment for wide range of potential confounders (IRR 2.70; 95% CI 1.744–4.19). The risk of NAFLD in GDM remained high (IRR 2.46: 95% CI 1.51–4.00) despite women being censored after they developed type 2 diabetes. The meta-analysis of 3 studies (including the current study) showed increased NAFLD risk in women with vs without GDM (OR 2.60; 95% CI 1.90–3.57, I2 = 0%). As our study is based on routine clinical diagnosis of NAFLD, this study could potentially have underestimated the risk of NAFLD development. Conclusions Women with GDM are at increased risk of developing NAFLD in their later life compared to women without GDM regardless of the development of type 2 diabetes. Clinicians should have a low threshold to investigate women with history of GDM for the presence of NAFLD. Further studies to identify screening strategies are needed.

Purpose: The clinical impact of next-generation sequencing (NGS) in patients with head and neck squamous cell carcinoma (HNSCC) has not been described. We aimed to evaluate the clinical impact of NGS in the routine care of patients with HNSCC and to correlate genomic alterations with clinical outcomes. Experimental Design: Single-center study examining targeted NGS platform used to sequence tumor DNA obtained from 213 HNSCC patients evaluated in outpatient head and neck oncology clinic between August 2011 and December 2014. We correlated tumor genomic profiling results with clinical outcomes. Results: PI3K/RTK pathway activation occurred frequently [activating PIK3CA mutation or amplification (13%), PTEN inactivation (3%), RAS activation (6%), EGFR or ERBB2 activation (9%)]. Alterations in pathways affecting cell-cycle regulation [CCND1 amplification (9%), CDKN2A inactivation (17%), BRCA2 inactivation (2%)] and squamous differentiation [NOTCH1 inactivation (8%) andEP300 inactivation (6%)] were identified. PIK3CA amplification (n = 43), not PIK3CA mutation, was associated with significantly poorer progression-free survival (P = 0.0006). Oncogenic RAS mutations (n = 13) were associated with significantly poorer progression-free survival (P = 0.0001) and lower overall survival (P = 0.003). Eight patients with advanced, treatment-refractory HNSCC enrolled on clinical trials matched to tumor profiling results, and 50% achieved a partial response. Conclusions: Incorporation of NGS clinical assays into the routine care of patients with HNSCC is feasible and may readily facilitate enrollment into clinical trials of targeted therapy with a higher likelihood of success. Data can be utilized for discovery of genomic biomarkers of outcome. PIK3CA amplification and RAS mutations were frequently identified and associated with poorer prognosis in this cohort. Clin Cancer Res; 22(12); 2939–49. ©2016 AACR.

Background: Medical education is at cross roads today with a mismatch between students’ expectations of their performance and the reality. This led us to explore the reason for the academic decline. During our search, we found that metacognitive awareness plays a key role in moulding the learning skills of adult learners. Hence this study was conducted to evaluate the metacognitive awareness of medical students studying in the first year of MBBS. Methods: 100 first year medical students were included in the study and metacognitive awareness inventory questionnaire, a validated tool was administered to the students. This measures metacognitive knowledge and regulation. The results were obtained, tabulated and analysed. Results: Metacognitive awareness among medical students was average. Metacognitive knowledge was found to be significantly better than regulation. On comparing the genders, we note that females have better metacognitive regulation while males score higher in metacognitive knowledge which was statistically significant. Conclusions: The findings of the present study points towards the need of introduction of metacognitive strategies in the medical curriculum with more emphasis on problem based learning in order to make our learners become independent thinkers and efficient care givers.

BACKGROUND Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti-TNF therapies. Biosimilar anti-TNF monoclonal antibodies are increasingly used. Anti-TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately. AIM To cover the range of potential adverse reactions as a result of biologic therapy and specifically management of these events. METHODS A Medline and Pubmed search was undertaken. Search terms included were "anti-TNF," "infliximab" or "adalimumab" or "golimumab" combined with the keywords "ulcerative colitis" or "Crohn's disease" or "inflammatory bowel disease" and then narrowed to articles containing the keywords "complications," "side effects" or "adverse events" or "safety profile." International guidelines were also reviewed where relevant. RESULTS Adverse events discussed in this review include infusion reactions, blood disorders and infections (including bacterial, viral, fungal and opportunistic infections) as well as autoimmune, dermatological disorders, cardiac and neurological conditions. Malignancies including solid organ, haematological and those linked to viral disease are discussed. CONCLUSIONS Anti-TNF therapy has wide-ranging effects on the immune system resulting in a spectrum of potential adverse events in a small proportion of patients. Research advances are improving the understanding, recognition and management of these adverse events.

Objective: To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens. Methods: ZEB1 alterations were retrospectively identified from a cohort of 1,160 diffuse glioma patients. Epigenome-wide association scans (EWAS) were performed on available data. We determined the utility of ZEB1 as a prognostic indicator of patient survival in diffuse gliomas and assessed the value of ZEB1 to predict the efficacy of treating diffuse glioma patients with procarbazine, CCNU, and vincristine along with radiation at diagnosis. Decision curve analysis (DCA) was used to determine if ZEB1 added benefit to clinical decision-making over and above conventional methods. Results: Fifteen percent of diffuse glioma patients had a ZEB1 deletion. ZEB1 deletion was associated with poor overall survival (OS) with and without adjustment for age and tumor grade (adjusted HR: 4.25; 95% CI: 2.35 to 7.66; P < 0.001). Decision curve analysis confirmed that ZEB1 status with or without IDH1 was more beneficial to clinical decision making than conventional information such as age and tumor grade. We showed that ZEB1 regulates TERT expression, and patients with ZEB1 deletions likely subsume patients with mutant TERT expression in diffuse gliomas. ZEB1 influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment. Conclusion: We demonstrate the prognostic value of ZEB1 in diffuse glioma patients. We further determine ZEB1 to be a vital and influential molecular marker in clinical decisions that exceed conventional methods regarding whether to treat or not treat patients with diffuse glioma.

BackgroundIn 2014, in the United Kingdom, the government made a commitment to spend £3.6 million on the introduction of Skype video calling consultations in general practice, however the efficacy of such technology has not yet been explored fully.AimThe study aimed to explore the views and attitudes of General Practitioners (GPs) towards video consultation in primary care; specifically, in three broad areas∙The benefits of video consultations to patients and healthcare professionals.∙Potential problems with video consultation and its implementation.∙The cost-effectiveness of video consultation in this setting.MethodA convenience sample of the views of 12 general practitioners across two primary care centres in North London were identified using topic guide based semi-structured interviews. A thematic framework approach was used to analyse the data collected to isolate main and sub-themes.FindingsThree main themes were identified1.Technology – GPs expressed concerns about the ability of patients to use technology, the availability of technology and the quality of technology available.2.Utility – encompassing GP’s ideas about the usefulness of video consultations to patients, practitioners and the doctor–patient relationship. GPs presented mixed views on the extent to which video consultation would be useful.3.Practicality – covering the views of GPs on implementation and effects on workload. GPs unanimously felt that it was not a practical substitute for face-to-face consultation. There were mixed feelings about it being used as an alternative to telephone consultation.ConclusionGPs did see potential benefits to using video consultations but also expressed concerns that need to be addressed if they are to have full confidence in the system. The views of those who are going to use video consultation as a means of increasing patient access are paramount if such tools are to be a core part of primary care.

Background: Nutritional status can be difficult to assess. Bioelectrical impedance analysis (BIA)-derived phase angle (PA), and the plasma markers citrulline and transthyretin (pre-albumin) have the potential to assist, but the protocol of fasting and resting for BIA renders the investigation impractical for routine use, especially so in populations at high risk of malnutrition. Aims: 1- To clarify whether starving and resting are necessary for reliable measurement of PA. 2- To identify whether PA, citrulline and transthyretin correlate with nutritional status. Methods: Eighty consenting adult in-patients were recruited. Nutritional status was determined by subjective global assessment (SGA) used as gold standard. The Malnutrition Universal Screening Tool (MUST) was used and anthropometric measurements were performed. Serum was analysed for citrulline and transthyretin. PA was measured using Bodystat 4000. The PA was considered to define malnutrition when lower than reference ranges for sex and age, and severe malnutrition if more than 2 integers below the lower limit. Anthropometric measurements were categorised according to WHO reference centiles. Ordinal logistic regression estimated the strength of association of PA, citrulline and transthyretin with SGA. PA values in the different metabolic states were compared using paired t tests. Results: All 80 subjects completed the BIA and the nutritional assessments in the 3 different states; 14 declined to provide blood samples for the biochemical assays. Malnutrition was identified in 32 cases, severe malnutrition in 14 cases, the remaining 34 cases were deemed not to be malnourished. PA was strongly inversely associated with SGA (Odds Ratio [OR] per unit increase = 0.21, CI 0.12-0.37, p < 0.001). PA was not influenced by exercise (p=0.134) or food intake (p=0.184). Transthyretin was inversely associated with malnourished/severely malnourished states (OR = 0.98, 95% CI 0.97 – 0.99, p = 0.001), but had poorer predictive values than PA. There was no significant association between citrulline concentration and SGA (OR = 1.01, 95% CI 0.99-1.04, p = 0.348). Conclusions: The BIA-derived PA reliably identifies malnutrition. It is strongly associated with SGA but requires less skill and experience, and out-performs circulating transthyretin, rendering it a promising and less operator-dependent tool for assessing nutritional status in hospital patients. Our novel demonstration that fasting and bed-rest are unnecessary consolidates that position.

Background Identification of a microRNA (miRNA) pattern to be used as a biomarker for HNSCC is challenging given the heterogeneity of the disease and different methodologies used. To better define the field, we performed a prospective analysis of blood, tumor, and paired benign tissues in tongue squamous cell carcinoma (SCC) patients. Methods Plasma samples were collected prior to surgery, and paired tumor and benign tissue blocks were collected from tongue cancer resections. Circulating free and exosomal miRNA, and paired tumor and benign tissues miRNA were analyzed. TaqMan-based miRNA arrays were used to quantitate the expression of 747 human miRNAs. The comparative Ct method assessed the miRNA profile results, and Student’s t-test determined statistical significance between tumor and benign samples. Results Sixteen of 359 miRNAs detected were differentially expressed between paired tumor and benign tissue. Nine were upregulated, and seven downregulated in tumor tissue. All nine upregulated and six of seven downregulated tumor miRNAs were expressed in circulating exosomes. In contrast, eight of nine upregulated and four of seven downregulated tumor miRNAs were circulating free in the plasma. Conclusion An aberrantly expressed pattern of miRNA was identified in both tumor and plasma of patients with tongue SCC, suggesting this may be a biomarker for SCC of the oral tongue. Circulating exosomes appear to be a more reliable method for evaluation of circulating tumor-miRNA expression. Further studies with a larger cohort of patients and serial blood samples are needed to validate our findings.

Essentials We estimated the cardiovascular risk of patients with idiopathic thrombocytopenic purpura (ITP). The risk of cardiovascular disease was 38% higher in ITP patients compared with controls. Among the ITP patients, splenectomy was associated with higher cardiovascular disease. Clinicians should consider cardiovascular risk when managing ITP patients.Background Idiopathic thrombocytopenic purpura (ITP) is classically characterized by a transient or persistent decrease of platelet count. Mortality is higher in the ITP population than the general population, with a possible association with increased cardiovascular disease (CVD). Objectives The objective was to assess the strength of the association between ITP and CVD, with a secondary aim to assess the impact of splenectomy on CVD. Methods A population-based retrospective, open cohort study using clinical codes was performed using data from 6591 patients with ITP and 24 275 randomly matched controls (up to 1:4 ratio matched by age, sex, body mass index and smoking status). The main outcome was the risk of CVD, which included ischemic heart disease, stroke, trans-ischemic attack and heart failure. Adjusted incidence rate ratios were calculated using Poisson regression. Results During a median 6-year observation period there was a CVD diagnosis recorded in 392 (5.9%) ITP patients and 1114 (4.5%) control patients. There was an increased risk of developing CVD in the ITP cohort (incidence rate ratio [IRR], 1.38; 95% confidence interval [CI], 1.23-1.55), which remained robust even after a sensitivity analysis only including incident cases of ITP. Findings suggested that patients who had undergone splenectomy were at even further increased risk of developing CVD when compared with the ITP population who had not undergone splenectomy (adjusted IRR, 1.69; 95% CI, 1.22-2.34). Conclusion There is an increased risk of developing CVD in patients with ITP and even further increased risk for those patients with ITP who underwent splenectomy.

Background Osteoradionecrosis of the jaw (ORN) is an infrequent yet potentially devastating complication of radiation therapy to the head and neck region. Treatment options include antimicrobial therapy, local sequestrectomy, resection, and the use of hyperbaric oxygen (HBO). Published data on ORN are difficult to compare because of the lack of a universally accepted classification and staging system, and the literature on the use of HBO to either prevent or successfully manage ORN is controversial and inconclusive. Therefore, we aimed to establish a standard approach for using HBO at our institution. Materials and Methods A literature search was conducted of articles published in the English language between January 1980 and January 2016. Retrieved articles were evaluated by two independent reviewers. Isolated case reports, abstracts, case series, review articles, and cohort studies without a control group were excluded; summary data were extracted from the remaining studies. A panel of experts from Head and Neck Oncology and Oral Medicine from the Dana-Farber Cancer Institute and Brigham and Women’s Hospital reviewed the summary data and established multidisciplinary guidelines on the use of HBO for the prevention and management of ORN. Results Seven studies were evaluated and reviewed by the multidisciplinary panel. There was no consistent evidence in support of HBO for either the prevention or management of ORN. Conclusion Based on the available evidence and expert opinion, routine use of HBO for the prevention or management of ORN is not recommended and is rarely used at our institution.

Inflammatory bowel disease (IBD) mainly comprises of two separate inflammatory conditions: Crohn's disease (CD) and ulcerative colitis (UC). The aetiology of these conditions is still being explored with current evidence pointing towards a combination of environmental and genetic components. However, the pathophysiology is understood as a cytokine driven inflammatory response. There is significant association between IBD and dental conditions such as dental caries, other infections and periodontitis. Anti-inflammatory medications such as 5 aminosalicylic acid (5ASA), steroids and biological therapies are the treatment of choice for these chronic conditions, dependent on aetiology. Therefore, this article aims to educate dentists regarding possible implications IBD and its treatment can have for clinical practice and future research.

Purpose: Cancers may resist single-agent targeted therapies when the flux of cellular growth signals is shifted from one pathway to another. Blockade of multiple pathways may be necessary for effective inhibition of tumor growth. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR/PI3K or combined RAF/MEK inhibition but experienced a dramatic response when both drug regimens were combined. Experimental Design: Multi-region whole-exome sequencing of five diagnostic and four autopsy tumor biopsies was performed. Meta-analysis of DNA and RNA sequencing studies of ATC was performed. Results: Sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways, respectively. Meta-analysis demonstrated 10.3% cooccurrence of MAPK and PI3K pathway alterations in ATC. These tumors display a separate transcriptional profile from other ATCs, consistent with a novel subgroup of ATC. Conclusions: BRAF and PIK3CA mutations define a distinct subset of ATC. Blockade of the MAPK and PI3K pathways appears necessary for tumor response in this subset of ATC. This identification of synergistic activity between targeted agents may inform clinical trial design in ATC. Clin Cancer Res; 23(9); 2367–73. ©2016 AACR.

Ewing sarcoma (EWS) is an aggressive bone malignancy that mainly affects children and young adults. The mechanisms by which EWS (EWSR1) fusion genes drive the disease are not fully understood. CRM1 (XPO1) traffics proteins from the nucleus, including tumor suppressors and growth factors, and is overexpressed in many cancers. A small-molecule inhibitor of CRM1, KPT-330, has shown therapeutic promise, but has yet to be investigated in the context of EWS. In this study, we demonstrate that CRM1 is also highly expressed in EWS. shRNA-mediated or pharmacologic inhibition of CRM1 in EWS cells dramatically decreased cell growth while inducing apoptosis, cell-cycle arrest, and protein expression alterations to several cancer-related factors. Interestingly, silencing of CRM1 markedly reduced EWS–FLI1 fusion protein expression at the posttranscriptional level and upregulated the expression of the well-established EWS-FLI1 target gene, insulin-like growth factor binding protein 3 (IGFBP3), which inhibits IGF-1. Accordingly, KPT-330 treatment attenuated IGF-1–induced activation of the IGF-1R/AKT pathway. Furthermore, knockdown of IGFBP3 increased cell growth and rescued the inhibitory effects on IGF-1 signaling triggered by CRM1 inhibition. Finally, treatment of EWS cells with a combination of KPT-330 and the IGF-1R inhibitor, linsitinib, synergistically decreased cell proliferation both in vitro and in vivo. Taken together, these findings provide a strong rationale for investigating the efficacy of combinatorial inhibition of CRM1 and IGF-1R for the treatment of EWS. Cancer Res; 76(9); 2687–97. ©2016 AACR.

Background and Purpose: The purpose of this study was to assess factors causing delay in treatment of acute stroke in a tertiary care institute in South India. Methods: All clinically suspected cases of acute stroke presenting to the emergency department over a period of 1 year were prospectively followed up and data collected as per a preset pro forma. The various time intervals from stroke onset to definitive management and other pertinent data were collected. The time delays have been evaluated in the decision tree model: Chi-squared Automatic Interaction Detection. Significance was assessed at 5% level of significance (P < 0.05). Results: The mean prehospital time delay for all clinically suspected stroke (n = 361) in our institute was 716 min and the median time 190 min. The mean total in-hospital delay was 94.17 ± 54.5 min and median time being 82 min. The onset of symptoms to first medical contact was the main interval that influenced the prehospital delay. Computed tomographic (CT) diagnosis to stroke unit admission influenced the in-hospital delay the most. Conclusions: Lack of awareness regarding stroke leads to delayed seeking of treatment for the same. The factors that contribute to the in-hospital delay included patient admission procedure delay, lack of staff to transport the patient, and the distance between the stroke unit and CT room. Educating the community with regard to “stroke” and implementation of a better pre- and in-hospital stroke care system is a need of the hour in the country.

Background and Aim: Medicine, as we know, is a demanding career and students of medicine are prone to various forms of stress. Medical curriculum is stressful and requires the right type of personality to cope with the vast curriculum and study schedule. Stress adversely affects the students' academic performance and clinical skills. The sources of stress if studied along with the physiology of the learners' personality will help the students make the right career choice, thereby minimizing stress. Hence, if a student's personality is analyzed, a right career option may be made and stress may be reduced, to produce competent doctors. Therefore, the present study looks into the relationship of personality with the types of stresses faced by medical students. Methods: This cross-sectional study was conducted in a medical college in East India. Students were given two validated questionnaires. Medical student stress questionnaire assesses the sources of stresses in medical students and classifies it into six types. The big-five personality questionnaire classifies students as having five major personality traits. The data were analyzed by Student's t -test and Chi-square test using SPSS version 22. Results: Most of the medical students have academic stressors and agreeable personality traits with uniform gender distribution. Agreeable females have more academic stress. Overall, agreeable students have more statistically significant academic stress ( P Conclusion: An ideal doctor has an agreeable personality which most of our students have. The right blend of personality traits helps in alleviating stress, improving the academic outcome. The type of stress faced by the students and his/her personality should be kept in mind while helping students make a career choice and in curriculum designing.