Risk of drug-related upper gastrointestinal bleeding in the total population of the Netherlands: a time-trend analysis

ObjectiveMany prescribed and over-the-counter medications, for example, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with upper gastrointestinal bleeding (UGIB). Recently, a decrease in prescribing of NSAIDs was observed in the Netherlands, but whether a similar decreasing trend could be observed in the incidence of severe UGIB (either fatal or requiring hospitalisation), contingent on medication prescription, is unknown.DesignWe conducted a cohort study using Dutch national statistics on pharmacy claims, hospitalisation and mortality between 2013 and 2018. We explored the incidence of sex-specific and age-specific severe UGIB in four (sub)populations: (A) total population, (B) without a filled prescrption for NSAIDs, (C) without filled prescriptions for NSAIDs and antithrombotic agents, (D) without any risk factors for UGIB.ResultsThe cumulative incidence of severe UGIB did not decrease throughout the study period, regardless of the subgroup analysis. In the total population, it was 199 per 100 000 inhabitants (95% CI 197 to 201) in 2013–2014 and 260 (95% CI 258 to 263) in 2017–2018. The absolute risk of severe UGIB was 50% lower in the subgroup B than in the full cohort. It decreased further by 50% in the subgroup D when compared with subgroup B. The risk of severe UGIB was 1.5–1.9 fold higher in young women than in young men; an indication of over-the-counter NSAIDs use being more prevalent in women than men in this age group.ConclusionWe found no evidence to support a relationship between reduced prescribing of NSAIDs and the incidence of severe UGIB in the Netherlands since 2013. The relationship was also not observed when we removed the effect of risk factors.

Effect of COVID-19 on presentations of decompensated liver disease in Scotland

Background and aimsSARS-CoV-2 and consequent pandemic has presented unique challenges. Beyond the direct COVID-related mortality in those with liver disease, we sought to determine the effect of lockdown on people with liver disease in Scotland. The effect of lockdown on those with alcohol-related disease is of interest; and whether there were associated implications for a change in alcohol intake and consequent presentations with decompensated disease.MethodsWe performed a retrospective analysis of patients admitted to seven Scottish hospitals with a history of liver disease between 1 April and 30 April 2020 and compared across the same time in 2017, 2018 and 2019. We also repeated an intermediate assessment based on a single centre to examine for delayed effects between 1 April and 31 July 2020.ResultsWe found that results and outcomes for patients admitted in 2020 were similar to those in previous years in terms of morbidity, mortality, and length of stay. In the Scotland-wide cohort: admission MELD (Model for End-stage Liver Disease) (16 (12–22) vs 15 (12–19); p=0.141), inpatient mortality ((10.9% vs 8.6%); p=0.499) and length of stay (8 days (4–15) vs 7 days (4–13); p=0.140). In the Edinburgh cohort: admission MELD (17 (12–23) vs 17 (13–21); p=0.805), inpatient mortality ((13.7% vs 10.1%; p=0.373) and length of stay (7 days (4–14) vs 7 days (3.5–14); p=0.525)).ConclusionThis assessment of immediate and medium-term lockdown impacts on those with chronic liver disease suggested a minimal effect on the presentation of decompensated liver disease to secondary care.

Iron deficiency anaemia: pathophysiology, assessment, practical management

The WHO has recognised iron deficiency anaemia (IDA) as the most common nutritional deficiency in the world, with 30% of the population being affected with this condition. Although the most common causes of IDA are gastrointestinal bleeding and menstruation in women, decreased dietary iron and decreased iron absorption are also culpable causes. Patients with IDA should be treated with the aim of replenishing iron stores and returning the haemoglobin to a normal level. This has shown to improve quality of life, morbidity, prognosis in chronic disease and outcomes in pregnancy. Iron deficiency occurs in many chronic inflammatory conditions, including congestive cardiac failure, chronic kidney disease and inflammatory bowel disease. This article will provide an updated overview on diagnosis and management of IDA in patients with chronic conditions, preoperative and in pregnancy. We will discuss the benefits and limitations of oral versus intravenous iron replacement in each cohort, with an overview on cost analysis between the different iron formulations currently on the market.

Impact of statin treatment on non-invasive tests based predictions of fibrosis in a referral pathway for NAFLD

ObjectiveIn non-alcoholic fatty liver disease (NAFLD), fibrosis determines the risk of liver complications. Non-invasive tests (NITs) such as FIB-4, NAFLD Fibrosis Score (NFS) and Hepamet, have been proposed as a tool to triage NAFLD patients in primary care (PC). These NITs include AST±ALT in their calculations. Many patients with NAFLD take statins, which can affect AST/ALT, but it is unknown if statin affects NITs fibrosis prediction.MethodsWe included 856 patients referred through a standardised pathway from PC with a final diagnosis of NAFLD. 832 had reliable vibration controlled transient elastography (VCTE) measurements. We assessed the effects of statins on the association between NITs and VCTE at different fibrosis thresholds.Results129 out of 832 patients were taking a statin and 138 additional patients had indication for a statin. For any given FIB-4 value, patients on a statin had higher probabilities of high VCTE than patients not on a statin. Adjusting for body mass index, diabetes and age almost completely abrogated these differences, suggesting that these were related to patient’s profile rather to a specific effect of statins. Negative predictive values (NPVs) of FIB-4 <1.3 for VCTE >8, 10, 12 and 16 were, respectively, 89, 94, 96% and 100% in patients on a statin and 92, 95, 98% and 99% in patients not on a statin. Statins had similar impact on Hepamet predictions but did not modify NFS predictions.ConclusionIn patients with NAFLD referred from PC, those on statins had higher chances of a high VCTE for a given FIB-4 value, but this had a negligible impact on the NPV of the commonly used FIB-4 threshold (<1.3).

An 18-year-old girl with retrosternal burning discomfort: a bitter pill to swallow

Caustic injury secondary to impaction of ingested batteries is a potentially severe cause of oesophageal injury with an increasing incidence that reflects consumer trends and the utilisation of compact electronic devices. Delays to recognition and management are associated with increased risk of complications, morbidity and mortality. In this manuscript, we describe a case presentation and literature review of a patient presenting with upper oesophageal odynophagia after the deliberate ingestion of multiple foreign bodies.

Ustekinumab is effective for perianal fistulising Crohn's disease: a real-world experience and systematic review with meta-analysis

BackgroundPerianal Crohn’s disease (pCD) is a debilitating complication affecting up to 30% of Crohn’s disease (CD) population, leading to increased morbidity, mortality and decreased quality of life. Despite the growing armamentarium of medications for luminal CD, their efficacy in pCD remains poorly studied.AimTo determine the efficacy of ustekinumab, a biologic approved for luminal CD, in pCD through a retrospective cohort study and systematic review.MethodsA retrospective cohort study on patients with CD with active perianal fistulae treated with ustekinumab from September 2013 to August 2019 was performed to determine perianal fistula response and remission at 6 and 12 months after ustekinumab induction. A systematic review was performed to further establish rates of fistula response and remission with ustekinumab.ResultsAt 6 months, 48.1% (13/27) patients achieved fistula response with none achieving fistula remission on provider exam, and 59.3% (16/27) achieved patient-reported symptomatic improvement with 3.7% (1/27) achieving symptomatic remission. At 1 year, on provider exam, 55.6% (5/9) had fistula response with none achieving fistula remission, and 100% (9/9) had symptomatic improvement with 22.2% (2/9) achieving symptomatic remission. There were no major safety signals during 1-year follow-up. The systematic review of 25 studies found 44% (92/209) of patients with active perianal fistulas had a clinical response within 6 months of follow-up, and 53.9% (85/152) of patients with 12 months of follow-up achieved clinical response.ConclusionUstekinumab presents a safe and effective therapy for treatment of pCD. Prospective, randomised trials are needed to further elucidate long-term efficacy of ustekinumab for pCD.

Treatment-refractory ulcerative colitis responsive to indigo naturalis

BackgroundIndigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model.MethodsThis open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression.ResultsTen of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN.ConclusionIN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation.Trial registration numberNCT02442960.

Bacteraemia, sepsis and antibiotic resistance in Australian patients with cirrhosis: a population-based study

ObjectiveMultiple factors predispose patients with cirrhosis to sepsis and/or bacteraemia and this has a high mortality rate. Within different geographical regions there are marked differences in the prevalence of infection with multidrug-resistant organisms (MDR). This study examined risk factors for and outcomes of sepsis/bacteraemia in public hospital admissions with cirrhosis in the state of Queensland, Australia, over the last decade, along with the bacterial pathogens responsible and their antibiotic susceptibility profiles.DesignA population-based retrospective cohort study of public hospital admissions was conducted from 1 January 2008 to 31 December 2017. Hospital admissions for patients with a diagnosis of cirrhosis were categorised by the presence or absence of sepsis/bacteraemia. Clinical and sociodemographic information including cirrhosis aetiology, complications and comorbidities, and in-hospital mortality were examined using bivariate and multivariate analyses. In patients with bacteraemia, the type and prevalence of bacteria and antibiotic resistance was assessed.ResultsSepsis/bacteraemia was present in 3951 of 103 165 hospital admissions with a diagnosis of cirrhosis. Factors associated with sepsis/bacteraemia included disease aetiology, particularly primary sclerosing cholangitis (adj-OR 15.09, 95% CI 12.24 to 18.60), alcohol (adj-OR 2.90, 95% CI 2.71 to 3.09), Charlson Comorbidity Index ≥3 (adj-OR 3.54, 95% CI 3.19 to 3.93) and diabetes (adj-OR 1.87, 95% CI 1.74 to 2.01). Overall case-fatality rate among admissions with sepsis/bacteraemia was 27.7% (95% CI 26.3% to 29.1%) vs 3.7% (95% CI 3.6% to 3.8%) without sepsis/bacteraemia. In-hospital death was significantly associated with sepsis/bacteraemia (adj-OR 6.50, 95% CI 5.95 to 7.11). The most common organisms identified were Escherichia coli and Staphylococcus aureus, present in 22.9% and 18.1%, respectively, of the 2265 admissions with a positive blood culture. The prevalence of MDR bacteria was low (5.6%)ConclusionMorbidity and mortality related to sepsis/bacteraemia in patients with cirrhosis remains a critical clinical problem.

Risk of a post-colonoscopy colorectal cancer in patients with type 2 diabetes: a Danish population-based cohort study

ObjectivePrevalent type 2 diabetes (T2D) is associated with an increased risk of colorectal cancer and could impair the quality of bowel preparation for colonoscopy. This may in turn increase the risk of overlooked precancerous polyps and subsequent risk of post-colonoscopy colorectal cancer (PCCRC). We investigated whether patients with T2D are at increased risk of PCCRC compared with patients without T2D.DesignWe conducted a population-based cohort study of patients with T2D and without T2D undergoing colonoscopy in Denmark (1995–2015). We investigated the risk of PCCRC by calculating >6 to 36 months cumulative incidence proportions (CIPs) treating death and colectomy as competing risks. Using Cox proportional-hazards regression analyses, we also computed HRs of PCCRC, comparing patients with T2D and non-T2D. According to the World Endoscopy Organization guidelines, we calculated PCCRC 3-year rates to estimate the proportions of T2D and non-T2D CRC patients experiencing PCCRC.ResultsWe identified 29 031 patients with T2D and 333 232 patients without T2D undergoing colonoscopy. We observed 250 PCCRCs among patients with T2D and 1658 PCCRCs among patients without T2D. The >6 to 36 months CIP after a first-time colonoscopy was 0.64% (95% CI 0.55% to 0.74%) for T2D and 0.36% (95% CI 0.34% to 0.38%) for patients without T2D. The HRs of PCCRC were 1.43 (95% CI 1.21 to 1.72) after a first-time colonoscopy and 1.18 (95% CI 0.75 to 1.85) after a second-time colonoscopy. The PCCRC 3-year rate was 7.9% for patients with T2D and 7.4% for patients without T2D.ConclusionT2D may be associated with an increased HR of PCCRC.

A pilot feasibility trial of cognitive–behavioural therapy for insomnia in people with inflammatory bowel disease

ObjectivePoor sleep is common in inflammatory bowel disease (IBD), associated with worse overall disease course and predominantly attributable to insomnia. While cognitive–behavioural therapy for insomnia (CBT-I) is the recommended first-line treatment for chronic insomnia, it is untested in IBD. It is unclear if CBT-I will be as effective in this group given the extent of night-time symptoms people with IBD experience. Thus, we evaluated the feasibility and preliminary efficacy of CBT-I in IBD.DesignWe comprehensively assessed sleep in people with mild-to-moderately active IBD using questionnaires, daily diaries and actigraphy. People with significant insomnia symptoms were allocated to a single-arm, uncontrolled pilot feasibility study of gold-standard CBT-I treatment. They were then reassessed post-treatment.Results20 participants with IBD completed a baseline assessment. 10 were experiencing insomnia and were allocated to CBT-I. All participants who were offered CBT-I elected to complete it, and all completed 5/5 sessions. Participants rated treatment acceptability highly and daily diary and actigraphy completion rates were >95%. At baseline, participants with insomnia evidenced significantly worse sleep than participants without insomnia. Following CBT-I, participants reported significant improvements in diary and actigraphy measures of sleep continuity, dysfunctional sleep-related beliefs and IBD disease activity.ConclusionCBT-I was feasible and acceptable and demonstrated a signal for efficacy in the treatment of insomnia in IBD. Importantly, the improvements in sleep continuity were consistent with the extant literature. Future fully powered randomised controlled studies should evaluate whether treatment of insomnia can improve other aspects of IBD, including pain and inflammation.Trial registration numberNCT04132024.