Medication adherence in women with IBD of childbearing age likely associated with disease knowledge.

Background: Medication adherence in inflammatory bowel disease (IBD) is crucial, particularly during pregnancy. Unplanned pregnancies are common; therefore, efforts to maximise adherence should not be restricted to pregnant women. Objectives: We aimed to assess medication adherence in women with IBD of childbearing age, regardless of their reproduction plans. Design: We performed a multi-centre pilot questionnaire study of women with IBD age 18-45 years. Methods: Survey questions included patient demographics, disease history, and validated assessments of IBD and pregnancy knowledge, medication adherence and quality of life. The primary outcome was rates and predictors of medication adherence. Results: In all, 72 women [58.3% Crohn's disease (CD) and 37.5% ulcerative colitis] completed the survey. The median patient age was 30 years [interquartile range (IQR): 24.8-36.0) and 37.5% had children. Medication adherence was high (84%; median Medication Adherence Report Scale: 19.0/20; IQR: 17.0-20.0). Knowledge scores were adequate for both the Crohn's and Colitis Knowledge (CCKnow; median: 15.5/30; IQR: 12.3-18.0) and Crohn's and Colitis Pregnancy Knowledge (CCPKnow; median: 8.0/17; IQR: 4.0-11.0). Disease knowledge was predictive of high medication adherence (CCPKnow: p = 0.02; CCKnow: p ⩽ 0.01). Higher adherence was significantly associated with a diagnosis of CD (p = 0.01), exposure to biological agents (p = 0.03) and immunomodulators (p = 0.04), childbearing after diagnosis with IBD (p = 0.03), and correctly understanding the importance of delivery modality (p = 0.02) and IBD activity in pregnancy (p = 0.01). Conclusions: Following dedicated education at the IBD clinic, medication adherence, disease-specific and pregnancy-specific knowledge in women with IBD of childbearing age tends to be high. Unplanned pregnancies are frequent; therefore, we should aim to maximise medication adherence in all women of childbearing age to optimise maternofoetal outcomes if unexpected pregnancies occur.

Predicting COVID-19 incidence in French hospitals using human contact network analytics.

Background  COVID-19 was first detected in Wuhan, China, in 2019 and spread worldwide within a few weeks. The COVID-19 epidemic started to gain traction in France in March 2020. Subnational hospital admissions and deaths were then recorded daily and served as the main policy indicators. Concurrently, mobile phone positioning data have been curated to determine the frequency of users being colocalized within a given distance. Contrarily to individual tracking data, these can be a proxy for human contact networks between subnational administrative units. Methods  Motivated by numerous studies correlating human mobility data and disease incidence, we developed predictive time series models of hospital incidence between July 2020 and April 2021. We added human contact network analytics, such as clustering coefficients, contact network strength, null links or curvature, as regressors. Findings  We found that predictions can be improved substantially (by more than 50%) at both the national level and the subnational level for up to 2 weeks. Our subnational analysis also revealed the importance of spatial structure, as incidence in colocalized administrative units improved predictions. This original application of network analytics from colocalization data to epidemic spread opens new perspectives for epidemic forecasting and public health.

Uptake of a Switching Program for Patients Receiving Intravenous Infliximab and Vedolizumab to Subcutaneous Preparations.

BACKGROUND: Recent trials support the clinical efficacy and safety of subcutaneous infliximab (IFX) or vedolizumab (VDZ) for Inflammatory Bowel Disease (IBD). We evaluated the uptake and rationale for choosing to switch from intravenous infusions to subcutaneous injections. METHODS: Retrospective analysis of all adult patients receiving standard dosing IFX or VDZ maintenance therapy to investigate uptake of subcutaneous injections and the rationale for switching to subcutaneous injections. RESULTS: Of 232 eligible patients (total = 258: IFX = 190, VDZ = 68, and no longer eligible = 26), 58% of patients on IFX and 59% of patients on VDZ chose to switch to subcutaneous treatment. Age, sex, diagnosis, drug, line of treatment, and duration of treatment were not predictors for willingness to switch. Questionnaire responses (n = 51) demonstrate that the decision to switch was not influenced by COVID-19 exposure risk, impact on wider IBD service provision, impact on patient mental health, financial savings, seeking support following a switch, or a sense of independence managing IBD. Switchers (68%) were more motivated by time savings than non-switchers (25%; p = 0.0042). CONCLUSIONS: Switch uptake rates were 58%, with 90% of patients eligible to switch. Switch decision was influenced by time savings for patients but not by other patient-related factors.

Uptake of a switching program for patients receiving intravenous infliximab and vedolizumab to subcutaneous preparations

BackgroundRecent trials support the clinical efficacy and safety of subcutaneous biologic treatment for IBD maintenance therapy. Administration of subcutaneous injections could reduce the financial burden and time required to attend for infusions and allow IBD service providers to manage increasing clinical demand. We evaluated the uptake and rationale for choosing to switch from intravenous infusions to subcutaneous injections, including the impact of the Covid-19 pandemic on IBD service provision.MethodsWe performed a retrospective analysis including all adult patients receiving standard dosing maintenance Infliximab (IFX) or Vedolizumab (VDZ) therapy at a tertiary IBD centre. We investigated the uptake of the switch from intravenous infusions to subcutaneous injections and utilised a standardised patient questionnaire to determine the rationale for switching to subcutaneous injections or not, and to identify areas for improvement in IBD service provision for the switching process.ResultsOf 232 eligible patients (total 258, IFX = 190, VDZ = 68, no longer eligible = 26), 58% of patients on IFX and 59% of patients on VDZ chose to switch to SC treatment. There were no significant predictors for willingness to switch relating to patient age, sex, diagnosis, drug, line of treatment or duration of treatment (p>0.05).Patient questionnaire responses (n=52) demonstrate that a decision to switch was not influenced by Covid-19 exposure risk, the impact on wider IBD service provision, impact on patient mental health, financial savings, seeking support following a switch or a sense of independence managing IBD. Switchers (69%) were more motivated by time savings than non-switchers (24%). Most patients value face-to-face support at the IBD unit (90% switchers, 96% non-switchers) and utilise this time to seek support for managing IBD (75% switchers, 95% non-switchers).Most patients felt they received enough time (84% switchers, 76% non-switchers) and information (84% switchers, 77% non-switchers) to make a decision about switching. 61% of switchers reported concerns about the efficacy of SC injections compared to only 28% of non-switchers. Most patients report being happy with their decision (80% switchers, 76% non-switchers). 31%of non-switchers are now considering a switch.ConclusionsSwitch uptake rates were 58% with 90% of patients eligible to switch. We found no evidence that a decision to switch was influenced by age, sex, diagnosis, drug, line of treatment or duration of treatment. Non-switchers value face-to-face support at the IBD unit highly, and switchers value the time saved by administering injections at home. Most patients felt they were given sufficient time and information to decide on switching and did not have concerns regarding the safety or efficacy of subcutaneous injections.

British Society of Gastroenterology interim framework for addressing the COVID-19-related backlog in inflammatory bowel disease colorectal cancer surveillance

Inflammatory bowel disease (IBD) continues to carry an increased risk of colon cancer and national protocols for endoscopic surveillance are in place. [...]we propose the patient factors to consider when withdrawal of surveillance may be contemplated. Alternative strategies, such as the qFIT and virtual colonoscopy (either via CT or capsule), have not been used in IBD surveillance. qFIT, which measures the concentration of degraded haemoglobin and is raised in ulcerative colitis (UC) patients with active inflammation,12 13 has not been validated as a marker of IBD-related dysplasia. A faecal calprotectin threshold of >250 [micro]g/g to indicate disease activity is based on consensus and published evidence. 31-33 A three-point colonoscopy indicates a 45-minute procedure. 1st DR, first degree relative;CRC, colorectal cancer;FH, family history;IBD, inflammatory bowel disease;PSC, primary sclerosing cholangitis;qFIT, quantitative Faecal Immunochemical Test for haemoglobin The Gastroenterology GIRFT report has recommended the use of stool biomarkers to aid in the prioritisation of colonoscopy procedures on waiting lists.

Analysing different exposures identifies that wearing masks and establishing COVID-19 areas reduce secondary-attack risk in aged-care facilities

Background The COVID-19 epidemic has spread rapidly within aged-care facilities (ACFs), where the infection-fatality ratio is high. It is therefore urgent to evaluate the efficiency of infection prevention and control (IPC) measures in reducing SARS-CoV-2 transmission. Methods We analysed the COVID-19 outbreaks that took place between March and May 2020 in 12 ACFs using reverse transcription–polymerase chain reaction (RT–PCR) and serological tests for SARS-CoV-2 infection. Using maximum-likelihood approaches and generalized linear mixed models, we analysed the proportion of infected residents in ACFs and identified covariates associated with the proportion of infected residents. Results The secondary-attack risk was estimated at 4.1%, suggesting a high efficiency of the IPC measures implemented in the region. Mask wearing and the establishment of COVID-19 zones for infected residents were the two main covariates associated with lower secondary-attack risks. Conclusions Wearing masks and isolating potentially infected residents appear to be associated with a more limited spread of SARS-CoV-2 in ACFs.

Epidemiological and clinical insights from SARS-CoV-2 RT-PCR crossing threshold values, France, January to November 2020.

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.

Risk stratifying gastric ulcers: development and validation of a scoring system.

Objective: Debate is ongoing regarding the need for universal endoscopic follow-up to ensure gastric ulcer healing. We aimed to assess the value of follow-up oesophago-gastro-duodenoscopies (OGDs) for gastric ulcer healing and stratify patients according to risk of malignancy by developing a risk score. Design/method: All patients in National Health Service (NHS) Lothian with an index OGD and a diagnosis of gastric ulcer between 1 January 2014 and 31 December 2018 were identified. Data were analysed with logistic regression to identify factors significantly associated with a diagnosis of cancer; a risk score was derived and externally validated. Results: 778 patients were identified and 60.3% (469/778) of patients had a follow-up OGD. 8.6% (66/778) of patients were diagnosed with cancer. No cases of cancer were found on follow-up OGD of a benign appearing ulcer with negative biopsies. Macroscopic suspicion of malignancy was present at index OGD in 100% (3/3) of those diagnosed with cancer on subsequent OGDs. Older age (p=0.014), increased ulcer size (p<0.001) and non-antral location (p=0.030) were significantly associated with malignancy. A risk score (area under the curve (AUC) 0.868, p<0.001, minimum score=0, maximum score=6) was derived from these variables. 78.0% of patients with malignant ulcers scored ≥3, only 15.8% with benign ulcers scored ≥3 (negative predictive value (NPV) 97.4%). External validation yielded an AUC of 0.862 (p<0.001) and NPV of 98.6%; 84.0% of those with malignant ulcers scored ≥3. Conclusion: Ulcers with a combination of macroscopically benign appearances, at least six negative biopsies and a low risk score do not necessarily need endoscopic follow-up.

Comparative Outcomes of Budesonide MMX versus Prednisolone for Ulcerative Colitis: Results from a British Retrospective Multi-Centre Real-World Study.

During the COVID-19 pandemic many IBD units chose Budesonide MMX (Cortiment) as the first-line treatment for flares of ulcerative colitis (UC) in outpatients for its favourable side effect profile. This retrospective study of all UC patients treated with oral steroids between 1 March 2019-30 June 2019 and 1 March 2020-30 June 2020 aimed to compare Cortiment with Prednisolone in routine clinical practice. Outcomes included the need for hospitalisation for acute severe ulcerative colitis, symptoms at four weeks and end of treatment, and the need for rescue Prednisolone. The 2019 and 2020 cohorts did not differ at the baseline. Cortiment prescriptions rose from 24.5% in 2019 to 70.1% in 2020 (p < 0.001). At week four there were significant differences between 2019 and 2020 in mean bowel frequency (3.49 vs. 5.85, p = 0.001), rectal bleeding <50% (89.7% vs. 73.1% of patients, p = 0.039), and physician global assessment (PGA) (39.2% vs. 19.8% in remission, p = 0.045). There was no significant difference in hospital admissions, rectal bleeding, and PGA at week eight. Rescue Prednisolone was required in 10% of Cortiment patients in 2019 vs. 31.3% in 2020 (p = 0.058). Active IBD is associated with worse COVID-19 outcomes prompting the careful evaluation of the choice of first-line steroid for UC, as Cortiment was associated with worse outcomes at four weeks.

Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab.

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.

Memory is key in capturing COVID-19 epidemiological dynamics.

SARS-CoV-2 virus has spread over the world rapidly creating one of the largest pandemics ever. The absence of immunity, presymptomatic transmission, and the relatively high level of virulence of the COVID-19 infection led to a massive flow of patients in intensive care units (ICU). This unprecedented situation calls for rapid and accurate mathematical models to best inform public health policies. We develop an original parsimonious discrete-time model that accounts for the effect of the age of infection on the natural history of the disease. Analysing the ongoing COVID-19 in France as a test case, through the publicly available time series of nationwide hospital mortality and ICU activity, we estimate the value of the key epidemiological parameters and the impact of lock-down implementation delay. This work shows that including memory-effects in the modelling of COVID-19 spreading greatly improves the accuracy of the fit to the epidemiological data. We estimate that the epidemic wave in France started on Jan 20 [Jan 12, Jan 28] (95% likelihood interval) with a reproduction number initially equal to 2.99 [2.59, 3.39], which was reduced by the national lock-down started on Mar 17 to 24 [21, 27] of its value. We also estimate that the implementation of the latter a week earlier or later would have lead to a difference of about respectively -13k and +50k hospital deaths by the end of lock-down. The present parsimonious discrete-time framework constitutes a useful tool for now- and forecasting simultaneously community incidence and ICU capacity strain.

SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement.

SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success.

Detecting Rapid Spread of SARS-CoV-2 Variants, France, January 26-February 16, 2021.

Variants of severe acute respiratory syndrome coronavirus 2 raise concerns regarding the control of coronavirus disease epidemics. We analyzed 40,000 specific reverse transcription PCR tests performed on positive samples during January 26-February 16, 2021, in France. We found high transmission advantage of variants and more advanced spread than anticipated.

Impact of the coronavirus infectious disease (COVID-19) pandemic on the provision of inflammatory bowel disease (IBD) antenatal care and outcomes of pregnancies in women with IBD.

BACKGROUND: The impact of COVID-19 on pregnant inflammatory bowel disease (IBD) patients is currently unknown. Reconfiguration of services during the pandemic may negatively affect medical and obstetric care. We aimed to examine the impacts on IBD antenatal care and pregnancy outcomes. METHODS: Retrospective data were recorded in consecutive patients attending for IBD antenatal care including outpatient appointments, infusion unit visits and advice line encounters. RESULTS: We included 244 pregnant women with IBD, of which 75 (30.7%) were on biologics in whom the treatment was stopped in 29.3% at a median 28 weeks gestation. In addition, 9% of patients were on corticosteroids and 21.5% continued on thiopurines. The care provided during 460 patient encounters was not affected by the pandemic in 94.1% but 68.2% were performed via telephone (compared with 3% prepandemic practice; p<0.0001). One-hundred-ten women delivered 111 alive babies (mean 38.2 weeks gestation, mean birth weight 3324 g) with 12 (11.0%) giving birth before week 37. Birth occurred by vaginal delivery in 72 (56.4%) and by caesarean section in 48 (43.6%) cases. Thirty-three were elective (12 for IBD indications) and 15 emergency caesarean sections. Breast feeding rates were low (38.6%). Among 244 pregnant women with IBD, 1 suspected COVID-19 infection was recorded. CONCLUSION: IBD antenatal care adjustments during the COVID-19 pandemic have not negatively affected patient care. Despite high levels of immunosuppression, only a single COVID-19 infection occurred. Adverse pregnancy outcomes were infrequent.

[Mathematical epidemiology and modeling of the Covid-19 pandemic: issues and diversity]. / Épidémiologie mathématique et modélisation de la pandémie de Covid-19 : enjeux et diversité.

During the COVID-19 pandemic, the field of mathematical epidemiology experienced an exceptional production and media coverage of its work. Even though data and knowledge on the emerging disease were patchy, a wide variety of models were developed and applied in unprecedented timeframes, with the aim of estimating the reproduction number, the starting date of the epidemic or the cumulative incidence, but also to explore different scenarios of non-pharmaceutical interventions. Their results have made a major contribution to epidemiological surveillance and informed public health policy decisions.

Organisational changes and challenges for inflammatory bowel disease services in the UK during the COVID-19 pandemic.

OBJECTIVE: To determine the challenges in diagnosis, monitoring, support provision in the management of inflammatory bowel disease (IBD) patients and explore the adaptations of IBD services. METHODS: Internet-based survey by invitation of IBD services across the UK from 8 to 14 April 2020. RESULTS: Respondents from 125 IBD services completed the survey. The number of whole-time equivalent gastroenterologists and IBD nurses providing elective outpatient care decreased significantly between baseline (median 4, IQR 4-7.5 and median 3, IQR 2-4) to the point of survey (median 2, IQR 1-4.8 and median 2, IQR 1-3) in the 6-week period following the onset of the COVID-19 pandemic (p<0.001 for both comparisons). Almost all (94%; 112/119) services reported an increase in IBD helpline activity. Face-to-face clinics were substituted for telephone consultation by 86% and video consultation by 11% of services. A variation in the provision of laboratory faecal calprotectin testing was noted with 27% of services reporting no access to faecal calprotectin, and a further 32% reduced access. There was also significant curtailment of IBD-specific endoscopy and elective surgery. CONCLUSIONS: IBD services in the UK have implemented several adaptive strategies in order to continue to provide safe and high-quality care for patients. National Health Service organisations will need to consider the impact of these changes in current service delivery models and staffing levels when planning exit strategies for post-pandemic IBD care. Careful planning to manage the increased workload and to maintain IBD services is essential to ensure patient safety.