Real-World Outcomes of Patients Starting Intravenous and Transitioning to Subcutaneous Vedolizumab in Inflammatory Bowel Disease.

BACKGROUND: Real-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce. AIMS: To assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care. METHODS: Adult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP). RESULTS: Altogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (µg/g) decreased from 459 (185-1001) to 65 (26-227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152-1450) to 49 (20-275) in ulcerative colitis (n = 58; p < 0.001). CONCLUSION: Initiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ.

SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study.

OBJECTIVE: To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes considering testing policy and test-positivity-to-delivery interval. DESIGN: Nationwide cohort study. SETTING: Sweden. POPULATION: From the Pregnancy-Register we identified 88 593 singleton births, 11 March 2020-31 January 2021, linked to data on SARS-CoV-2-positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing-policy and test-positivity-to-delivery interval. MAIN OUTCOME MEASURES: Five-minute Apgar score, neonatal care admission, stillbirth and preterm birth. RESULTS: During pregnancy, SARS-CoV-2 test-positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non-universal testing. There were generally lower risks associated with SARS-CoV-2 under universal than non-universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62-3.11) in women testing positive ≤10 days before delivery under universal testing. There was no significant association with 5-minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24-1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10-5.20). Compared with term births (2.1%), test-positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60-4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62-2.02). CONCLUSIONS: Testing policy and timing of test-positivity impact associations between SARS-CoV-2-positivity and pregnancy outcomes. Under non-universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. TWEETABLE ABSTRACT: Testing policy and time from SARS-CoV-2 infection to delivery influence the association with pregnancy outcomes.

Direct oral anticoagulant use and risk of severe COVID-19.

BACKGROUND: Hypercoagulability and thromboembolism are prominent features of severe COVID-19, and ongoing anticoagulant use might be protective. METHODS: We conducted a nationwide register-based cohort study in Sweden, February through May, 2020, to assess whether ongoing direct oral anticoagulant (DOAC) use was associated with reduced risk of hospital admission for laboratory-confirmed COVID-19, or a composite of intensive care unit (ICU) admission or death due to laboratory-confirmed COVID-19. RESULTS: DOAC use (n = 103 703) was not associated with reduced risk of hospital admission for COVID-19 (adjusted hazard ratio [aHR] [95% confidence interval] 1.00 [0.75-1.33] vs. nonuse atrial fibrillation comparator [n = 36 875]; and aHR 0.94 [0.80-1.10] vs. nonuse cardiovascular disease comparator [n = 355 699]), or ICU admission or death due to COVID-19 (aHRs 0.76 [0.51-1.12], and 0.90 [0.71-1.15], respectively). CONCLUSION: Ongoing DOAC use was not associated with reduced risk of severe COVID-19, indicating that prognosis would not be modified by early outpatient DOAC initiation.

Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study.

BACKGROUND AND PURPOSE: Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD. METHODS: We performed a population-based cohort study using Swedish national register data. Adults aged ≥35 years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics. RESULTS: Amongst the study population (N = 4 670 423), 34 868 (0.75%) had a history of CDI. A total of 165 and 47 035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2 years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups. CONCLUSIONS: Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.

Decrease in primary but not in secondary abdominal surgery for Crohn's disease: nationwide cohort study, 1990-2014.

BACKGROUND: Treatment of patients with Crohn's disease has evolved in recent decades, with increasing use of immunomodulatory medication since 1990 and biologicals since 1998. In parallel, there has been increased use of active disease monitoring. To what extent these changes have influenced the incidence of primary and repeat surgical resection remains debated. METHODS: In this nationwide cohort study, incident patients of all ages with Crohn's disease, identified in Swedish National Patient Registry between 1990 and 2014, were divided into five calendar periods of diagnosis: 1990-1995 and 1996-2000 with use of inpatient registries, 2001, and 2002-2008 and 2009-2014 with use of inpatient and outpatient registries. The cumulative incidence of first and repeat abdominal surgery (except closure of stomas), by category of surgical procedure, was estimated using the Kaplan-Meier method. RESULTS: Among 21 273 patients with Crohn's disease, the cumulative incidence of first abdominal surgery within 5 years of Crohn's disease diagnosis decreased continuously from 54·8 per cent in 1990-1995 to 40·4 per cent in 1996-2000 (P < 0·001), and again from 19·8 per cent in 2002-2008 to 17·3 per cent in 2009-2014 (P < 0·001). Repeat 5-year surgery rates decreased from 18·9 per cent in 1990-1995 to 16·0 per cent in 1996-2000 (P = 0·009). After 2000, no further significant decreases were observed. CONCLUSION: The 5-year rate of surgical intervention for Crohn's disease has decreased significantly, but the rate of repeat surgery has remained stable despite the introduction of biological therapy.

ANTECEDENTES: El tratamie nto de pacientes con enfermedad de Crohn ha evolucionado en las últimas décadas con un uso cada vez mayor de medicamentos inmunomoduladores desde 1990 y tratamientos biológicos desde 1998. Al mismo tiempo, ha aumentado la utilidad de la vigilancia activa de la enfermedad. Hasta qué punto estos cambios han influido en la incidencia de la resección quirúrgica primaria y repetida sigue siendo objeto de debate. MÉTODOS: Estudio de cohortes a nivel nacional de pacientes incidentes con enfermedad de Crohn de todas las edades identificados en el registro sueco nacional de pacientes entre 1990-2014, que se dividió en cinco períodos de diagnóstico: 1990-1995 y 1996-2000 con el uso de registros de pacientes hospitalizados, 2001, y 2002-2008 y 2009-2014 con uso de registros de pacientes ambulatorios y hospitalizados. Se estimó la incidencia acumulada de la primera cirugía abdominal y de las cirugías abdominales subsiguientes (excepto el cierre de estomas), por categoría de procedimiento quirúrgico, mediante el método de Kaplan-Meier. RESULTADOS: Entre 21.273 pacientes con enfermedad de Crohn, la incidencia acumulada de la primera cirugía abdominal durante los 5 años posteriores al diagnóstico de la enfermedad disminuyó continuamente del 54,8% en la cohorte 1990-1995 al 40,4% en la cohorte 1996-2000 (P < 0,001) y nuevamente del 19,8% en cohorte 2002-2008 al 17,3% en la cohorte 2009-2014 (P < 0,001). Las tasas cirugías iterativas a los 5 años disminuyeron de 18,9% en la cohorte 1990-1995 a 16,0% en la cohorte 1996-2000 (P = 0,017). Después del 2000, no se observaron más disminuciones significativas. CONCLUSIÓN: La tasa de intervención quirúrgica a los 5 años para la enfermedad de Crohn ha disminuido significativamente, pero la cirugía iterativa se ha mantenido estable a pesar de la introducción de la terapia biológica.

The risk of epilepsy in children with celiac disease: a population-based cohort study.

BACKGROUNDAND PURPOSE: The purpose was to estimate the risk of epilepsy in a cohort of young individuals with celiac disease (CD) compared to that of matched references. METHODS: The cohort consisted of 213 635 individuals born during 1989-2011 and residing in Friuli-Venezia Giulia (Italy). 1215 individuals affected by CD and 6075 reference individuals matched by sex and age were identified. Epilepsy was defined by means of hospital diagnosis or drug prescriptions. Conditional logistic regression was used to estimate the odds ratios (ORs) of having epilepsy amongst individuals with CD, before CD diagnosis and in the entire period, compared with those of their matched references. Cox regression was used to calculate the hazard ratios for epilepsy diagnosed after CD diagnosis. Different definitions of epilepsy were used for sensitivity analyses. RESULTS: Thirty-one (2.6%) individuals with CD and 78 (1.3%) reference individuals had epilepsy [adjusted OR 2.03; 95% confidence interval (CI) 1.33-3.10]. The risk of epilepsy was increased prior to CD (adjusted OR 2.29; 95% CI 1.33-3.94), with similar estimates after CD diagnosis (adjusted hazard ratio 1.96; 95% CI 0.95-4.02). The increased risk of epilepsy was not explained by a peak in epilepsy diagnosis just around CD diagnosis. Sex stratification found a significantly higher risk of epilepsy amongst female individuals with CD. Sensitivity analyses confirmed the positive association between CD and epilepsy. CONCLUSION: Children and youths with CD were at increased risk of epilepsy. Patients with epilepsy without a clear etiology should be screened for CD since an early diagnosis and treatment might improve the response to antiepileptic therapies.

Investigating fetal growth restriction and perinatal risks in appropriate for gestational age infants: using cohort and within-sibling analyses.

OBJECTIVE: Fetal growth restriction refers to fetuses that fail to reach their growth potential. Studies within siblings may be useful to disclose fetal growth restriction in appropriate for gestational age (AGA) infants. We analysed associations between birthweight percentiles and perinatal risks in AGA infants, using both population-based and within-sibling analyses. DESIGN: Population-based cohort study. SETTING AND SAMPLE: Using nation-wide Swedish registries (1987-2012), we identified 2 134 924 singleton AGA births (10th-90th birthweight percentile for gestational age), of whom 1 377 326 were full siblings. METHODS: Unconditional Poisson regression was used for population analyses, and conditional (matched) Poisson regression for within-sibling analyses. We estimated associations between birthweight percentiles and stillbirth, neonatal mortality, and morbidity, using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: Stillbirth and neonatal mortality risks declined with increasing birthweight percentiles, but the declines were larger in within-sibling analyses. Compared with the reference group (40th to <60th percentile), IRRs (95% CIs) of stillbirth for the lowest and highest percentile groups (10th to <25th and 75th-90th percentiles, respectively) were 1.87 (1.72-2.03) to 0.76 (0.68-0.85) in population analysis and 2.60 (2.27-2.98) and 0.43 (0.36-0.50) in within-sibling analysis. Neonatal morbidity risks in term non-malformed infants with low birthweight percentiles were generally only increased in within-sibling analyses. CONCLUSION: Using birthweight information from siblings may help to define fetal growth restriction in AGA infants. TWEETABLE ABSTRACT: Size of siblings helps to detect growth-restricted infants with seemingly normal birthweights.

Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis.

BACKGROUND: Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis. AIMS: To investigate the prevalence of CD among individuals with osteoporosis. METHODS: We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with "fractures", "bone disease", "bone density", "densitometry", "osteoporos*", "osteomal*", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression. RESULTS: We identified eight relevant studies, comprising data from 3188 individuals with osteoporosis. Of these, 59 individuals (1.9%) had CD. A weighted pooled analysis demonstrated biopsy-confirmed CD in 1.6% (95% CI = 1.1%-2.0%) of individuals with osteoporosis. The heterogeneity was moderate (I2  = 40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n = 814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI = 1.2%-2.0%). CONCLUSIONS: About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.

Persistent mucosal damage and risk of epilepsy in people with celiac disease.

BACKGROUND AND PURPOSE: Celiac disease (CD) is associated with an increased risk of developing epilepsy, a risk that persists after CD diagnosis. A significant proportion of patients with CD have persistent villous atrophy (VA) on follow-up biopsy. The objective of this study was to determine whether persistent VA on follow-up biopsy affected long-term epilepsy risk and epilepsy-related hospital emergency admissions. METHODS: This was a nationwide cohort study. We identified all people in Sweden with histological evidence of CD who underwent a follow-up small intestinal biopsy (1969-2008). We compared those with persistent VA with those who showed histological improvement, assessing the development of epilepsy and related emergency hospital admissions (defined according to relevant International Classification of Diseases codes in the Swedish Patient Register). Cox regression analysis was used to assess outcome measures. RESULTS: Villous atrophy was present in 43% of 7590 people with CD who had a follow-up biopsy. The presence of persistent VA was significantly associated with a reduced risk of developing newly-diagnosed epilepsy (hazard ratio, 0.61; 95% confidence interval, 0.38-0.98). On stratified analysis, this effect was primarily amongst males (hazard ratio, 0.35; 95% confidence interval, 0.15-0.80). Among the 58 patients with CD with a prior diagnosis of epilepsy, those with persistent VA were less likely to visit an emergency department with epilepsy (hazard ratio, 0.37; 95% confidence interval, 0.09-1.09). CONCLUSIONS: In a population-based study of individuals with CD, persisting VA on follow-up biopsy was associated with reduced future risk of developing epilepsy but did not influence emergency epilepsy-related hospital admissions. The mechanism as to why persistent VA confers this benefit requires further exploration.

Duration and magnitude of postoperative risk of venous thromboembolism after planned inguinal hernia repair in men: a population-based cohort study.

PURPOSE: Little is known regarding the magnitude and timing of the risk of VTE following inguinal hernia surgery. We aimed to determine the absolute and relative rates of venous thromboembolism (VTE) following planned inguinal hernia repair. METHODS: We analysed male adults with a first inguinal hernia repair with no prior record of VTE from the Clinical Practice Research Datalink, linked to the Hospital Episode Statistics (2001-2011). Crude rates and adjusted hazard ratios (HR) of the first VTE were calculated using Cox regression analysis to compare specific time periods following the surgery compared to the general population. RESULTS: We identified 28,782 men who underwent an inguinal hernia repair with 53 (0.18%) having a first VTE in the 90 days following surgery. The overall rate of VTE in the first 90 days following surgery was 7.61 per 1000 person years (pyrs) (95% CI 5.82-9.96). Increasing age, a body mass index > 30 kg/m2 and an in-patient procedure were associated with an increased risk of VTE, when compared to the general population. The risk of VTE was highest in the 1st month following the surgery with a 2.3- (aHR 2.33; 95% CI 1.09-4.99) and 3.5- (aHR 3.47; 95% CI 2.07-5.83) fold increased risk compared to the general population for both day case and planned in-patient procedures, respectively. CONCLUSIONS: Reassuringly, the absolute rates of VTE following inguinal hernia repair are low. Patients should be informed that their peak risk of VTE is during the 1st month following the surgery. Further studies on the optimum duration of thromboprophylaxis following surgery are required in high-risk patients undergoing hernia repair.

Childhood onset inflammatory bowel disease and risk of cancer: a Swedish nationwide cohort study 1964-2014.

Objective To assess risk of cancer in patients with childhood onset inflammatory bowel disease in childhood and adulthood.Design Cohort study with matched general population reference individuals using multivariable Cox regression to estimate hazard ratios.Setting Swedish national patient register (both inpatient and non-primary outpatient care) 1964-2014.Participants Incident cases of childhood onset (<18 years) inflammatory bowel disease (n=9405: ulcerative colitis, n=4648; Crohn's disease, n=3768; unclassified, n=989) compared with 92 870 comparators from the general population matched for sex, age, birth year, and county.Main outcome measures Any cancer and cancer types according to the Swedish Cancer Register.Results During follow-up through adulthood (median age at end of follow-up 27 years), 497 (3.3 per 1000 person years) people with childhood onset inflammatory bowel disease had first cancers, compared with 2256 (1.5 per 1000 person years) in the general population comparators (hazard ratio 2.2, 95% confidence interval 2.0 to 2.5). Hazard ratios for any cancer were 2.6 in ulcerative colitis (2.3 to 3.0) and 1.7 in Crohn's disease (1.5 to 2.1). Patients also had an increased risk of cancer before their 18th birthday (2.7, 1.6 to 4.4; 20 cancers in 9405 patients, 0.6 per1000 person years). Gastrointestinal cancers had the highest relative risks, with a hazard ratio of 18.0 (14.4 to 22.7) corresponding to 202 cancers in patients with inflammatory bowel disease. The increased risk of cancer (before 25th birthday) was similar over time (1964-1989: 1.6, 1.0 to 2.4; 1990-2001: 2.3, 1.5 to 3.3); 2002-06: 2.9, 1.9 to 4.2; 2007-14: 2.2, 1.1 to 4.2).Conclusion Childhood onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both in childhood and later in life. The higher risk of cancer has not fallen over time.

Anti-TNF treatment in Crohn's disease and risk of bowel resection-a population based cohort study.

BACKGROUND: TNF inhibitors (TNFi) have been shown to reduce the need for surgery in Crohn's disease, but few studies have examined their effect beyond the first year of treatment. AIM: To conduct a register-based observational cohort study in Sweden 2006-2014 to investigate the risk of bowel resection in bowel surgery naïve TNFi-treated Crohn's disease patients and whether patients on TNFi ≥12 months are less likely to undergo bowel resection than patients discontinuing treatment before 12 months. METHODS: We identified all individuals in Sweden with Crohn's disease through the Swedish National Patient Register 1987-2014 and evaluated the incidence of bowel resection after first ever dispensation of adalimumab or infliximab from 2006 and up to 7 years follow-up. RESULTS: We identified 1856 Crohn's disease patients who had received TNFi. Among these patients, 90% treatment retention was observed at 6 months after start of TNFi and 65% remained on the drug after 12 months. The cumulative rates of surgery in Crohn's disease patients exposed to TNFi years 1-7 were 7%, 13%, 17%, 20%, 23%, 25% and 28%. Rates of bowel resection were similar between patients with TNFi survival <12 months and ≥12 months respectively (P=.27). No predictors (eg, sex, age, extension or duration of disease) for bowel resection were identified. CONCLUSIONS: The risk of bowel resection after start of anti-TNF treatment is higher in regular health care than in published RCTs. Patients on sustained TNFi treatment beyond 12 months have bowel resection rates similar to those who discontinue TNFi treatment earlier.

Prevalence of paediatric inflammatory bowel disease in Sweden: a nationwide population-based register study.

BACKGROUND: We evaluated the impact of different case definition algorithms on the prevalence of paediatric inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) and to compare the occurrence of certain diseases compared to matched controls. METHODS: Paediatric patients (<18 years) were identified via ICD codes for UC and CD in Swedish registers between 1993 and 2010 (n = 1432). Prevalence was defined as ≥2 IBD-related visits. Prevalence of treated children in 2010 was defined as ≥2 IBD-related visits with one visit and ≥1 dispensed IBD-related drug prescription in 2010. To test the robustness of the estimates, prevalence was also calculated according to alternative case definitions. The presence of rheumatic, hepatobiliary, pancreatic, and dermatologic diseases were compared with age-/sex-/county-of-residence-matched general population controls. RESULTS: The IBD prevalence was 75/100,000 (CD: 29/100,000; UC: 30/100,000; patients with IBD-U: 16/100,000). Prevalence of treated disease in 2010 was 62/100,000 (CD: 23/100,000; UC: 25/100,000; patients with IBD-U: 13/100,000). When age restrictions were employed, the prevalence estimate decreased (<17y: 61/100,000, <16y: 49/100,000 and <15y: 38/100,000). Compared to general population controls (n = 8583), children with IBD had a higher prevalence of dermatologic (4.7% vs. 0.6%), hepatobiliary (including primary sclerosing cholangitis) (5.5% vs. 0.1%), pancreatic (1.7% vs. 0%) and rheumatic diseases (7.2% vs. 1.2%; all P < 0.01). CONCLUSIONS: The overall prevalence of paediatric IBD in Sweden was similar to that in earlier regional cohorts. IBD patients had a higher prevalence of comorbid conditions than matched general population controls.

Coeliac disease and invasive pneumococcal disease: a population-based cohort study.

Severe infections are recognized complications of coeliac disease (CD). In the present study we aimed to examine whether individuals with CD are at increased risk of invasive pneumococcal disease (IPD). To do so, we performed a population-based cohort study including 29 012 individuals with biopsy-proven CD identified through biopsy reports from all pathology departments in Sweden. Each individual with CD was matched with up to five controls (n = 144 257). IPD events were identified through regional and national microbiological databases, including the National Surveillance System for Infectious Diseases. We used Cox regression analyses to estimate hazard ratios (HRs) for diagnosed IPD. A total of 207 individuals had a record of IPD whereas 45/29 012 had CD (0·15%) and 162/144 257 were controls (0·11%). This corresponded to a 46% increased risk for IPD [HR 1·46, 95% confidence interval (CI) 1·05-2·03]. The risk estimate was similar after adjustment for socioeconomic status, educational level and comorbidities, but then failed to attain statistical significance (adjusted HR 1·40, 95% CI 0·99-1·97). Nonetheless, our study shows a trend towards an increased risk for IPD in CD patients. The findings support results seen in earlier research and taking that into consideration individuals with CD may be considered for pneumococcal vaccination.

Risk of symptomatic venous thromboembolism following emergency appendicectomy in adults.

BACKGROUND: Appendicectomy is the commonest intra-abdominal emergency surgical procedure, and little is known regarding the magnitude and timing of the risk of venous thromboembolism (VTE) after surgery. This study aimed to determine absolute and relative rates of symptomatic VTE following emergency appendicectomy. METHODS: A cohort study was undertaken using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data of patients who had undergone emergency appendicectomy from 2001 to 2011. Crude rates and adjusted incidence rate ratios (IRRs) for VTE were calculated using Poisson regression, compared with baseline risk in the year before appendicectomy. RESULTS: A total of 13 441 patients were identified, of whom 56 (0·4 per cent) had a VTE in the first year after surgery. The absolute rate of VTE was highest during the in-hospital period, with a rate of 91·29 per 1000 person-years, which was greatest in those with a length of stay of 7 days or more (267·12 per 1000 person-years). This risk remained high after discharge, with a 19·1- and 6·6-fold increased risk of VTE in the first and second months respectively after discharge, compared with the year before appendicectomy (adjusted IRR: month 1, 19·09 (95 per cent c.i. 9·56 to 38·12); month 2, 6·56 (2·62 to 16·44)). CONCLUSION: The risk of symptomatic VTE following appendicectomy is relatively high during the in-hospital admission and remains increased after discharge. Trials of extended thromboprophylaxis are warranted in patients at particularly high risk.