Post-migration HIV acquisition: A systematic review and meta-analysis.

Migrants in Europe face a disproportionate burden of HIV infection; however, it remains unclear if this can be prevented through public health interventions in host countries. We undertake a systematic review and meta-analysis to estimate post-migration HIV acquisition (PMHA) as a proportion of all HIV cases in European migrants. MEDLINE, EMBASE, Global Health, HMIC, and Cochrane Library were searched with terms capturing 'HIV', 'migration', and 'Europe'. Data relating to the proportion of HIV acquired following migration were extracted and random-effects model (REM) meta-analysis was undertaken to calculate a pooled estimate for the proportion of PMHA in European countries. Subgroup meta-analysis was undertaken for PMHA by migrant demographic characteristics and host country. Fifteen articles were included for systematic review following retrieval and screening of 2,320 articles. A total of 47,182 migrants in 11 European countries were included in REM meta-analysis, showing an overall PMHA proportion of 0.30 (95% CI: 0.23-0.38). Subgroup analysis showed no significant difference in PMHA between host country and migrant demographic characteristics. This work illustrates that migrants continue to be at high risk of HIV acquisition in Europe. This indicates the need for targeted screening and HIV prevention interventions, ensuring resources are appropriately directed to combat the spread of HIV.

Impact of immunosuppressive therapy on SARS-CoV-2 mRNA vaccine effectiveness in patients with immune-mediated inflammatory diseases: a Danish nationwide cohort study.

OBJECTIVE: Patients receiving immunosuppressives have been excluded from trials for SARS-CoV-2 vaccine efficacy. Investigation of immunosuppressants' impact on effectiveness of vaccines, particularly in patients with immune-mediated inflammatory diseases (IMID), is therefore required. DESIGN: We performed a nationwide cohort study to assess the risk of COVID-19 infection in vaccinated patients with IMID exposed to immunosuppressives compared with IMID unexposed to immunosuppressives. Exposure to immunosuppressives in the 120 days before receiving the second SARS-CoV-2 mRNA vaccination was assessed. Patients were followed from date of second vaccination and weighted Cox models were used to estimate the risk of infection associated with immunosuppressives. Secondary outcomes included hospitalisation and death associated with a positive SARS-CoV-2 test. Risk of infection by immunosuppressant drug class was also analysed. SETTING: This study used population-representative data from Danish national health registries in the period from 1 January to 30 November 2021. RESULTS: Overall, 152 440 patients were followed over 19 341 person years. Immunosuppressants were associated with a significantly increased risk of infection across IMID (HR: 1.4, 95% CI 1.2 to 1.5), in inflammatory bowel disease (IBD) (HR: 1.6, 95% CI 1.4 to 1.9) and arthropathy (HR: 1.3, 95% CI 1.1 to 1.4) but not psoriasis (HR: 1.1, 95% CI 0.9 to 1.4). Immunosuppressants were also associated with an increased risk of hospitalisation across IMID (HR: 1.4, 95% CI 1.1 to 2.0), particularly in IBD (HR: 2.1, 95% CI 1.0 to 4.1). No significantly increased risk of death in immunosuppressant exposed patients was identified. Analyses by immunosuppressant drug class showed increased COVID-19 infection and hospitalisation with anti-tumour necrosis factor (TNF), systemic corticosteroid, and rituximab and other immunosuppressants in vaccinated patients with IMID. CONCLUSION: Immunosuppressive therapies reduced effectiveness of mRNA SARS-CoV-2 vaccination against infection and hospitalisation in patients with IMID. Anti-TNF, systemic corticosteroids, and rituximab and other immunosuppressants were particularly associated with these risks.

Risk of Cervical Cancer in Inflammatory Bowel Disease: A Meta-Analysis of Population-Based Studies.

INTRODUCTION: There is increased risk of several malignancies in inflammatory bowel disease (IBD). However, evidence regarding risk of cervical cancer in IBD is conflicting. We aimed to investigate the risk of cervical cancer in IBD by undertaking a systematic review and meta-analysis of unselected, population-based studies. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched using Medical Subject Heading terms, and 2 reviewers independently screened results. Pooled hazard ratios (HRs) were calculated using random effects model meta-analysis for risk of cervical cancer in IBD. Subgroup meta-analysis was undertaken to assess risk of cervical cancer by IBD subtype (Crohn's disease and ulcerative colitis), treatment exposure, and grade of lesion. RESULTS: We screened 1,393 articles to identify 5 population-based studies, including 74,310 patients with IBD and 2,029,087 reference patients, across 5 different countries. Pooled random effects model meta-analysis of these studies did not show statistically significant increased risk for cervical cancer in IBD compared with reference populations (HR: 1.24; 95% confidence interval [CI]: 0.94-1.63). Meta-analysis by grade of lesion showed increased risk of low-grade cervical lesions (HR: 1.15; 95% CI: 1.04-1.28). Meta-analysis by disease subtype indicated no statistically significant increased risk in Crohn's disease (HR: 1.36; 95% CI: 0.83-2.23) or ulcerative colitis (HR: 0.95; 95% CI: 0.72-1.25) or in patients treated with antitumor necrosis factor (HR: 1.19; 95% CI: 0.64-2.21) or thiopurines (HR: 0.96; 95% CI: 0.60-1.50). DISCUSSION: This meta-analysis of high-quality, unselected population-based studies shows no statistically significant increased risk of cervical cancer in patients with IBD. There is, however, increased risk of low-grade cervical lesions compared with the general population.

Shared environment and colorectal cancer: A Nordic pedigree registry-based cohort study.

Risk of colorectal cancer (CRC) increases in relatives of patients with CRC. The extent to which this is attributable to genetic predisposition or shared environment is unclear. We explored this question using nationwide cohorts from Denmark, Finland and Sweden. From 1977 to 2013, we identified 359 879 individuals with a CRC diagnosis and 2 258 870 of their relatives who we followed for CRC incidence. We calculated standardized incidence ratios (SIR) and 95% confidence intervals (CI) for CRC in individuals with an affected relative. We used nationwide household and pedigree data along with national SIR estimates to calculate risk ratios (RR) for the contribution of shared household environment, childhood environment and genetic relationship to CRC risk in those with an affected relative. SIR of CRC was increased for individuals with an affected relative, across all countries and ages. For those with an affected parent, the SIR was 1.65 (95% CI: 1.61-1.69), 1.98 (95% CI: 1.87-2.09), for those with an affected sibling and 2.14 (95% CI: 1.84-2.49) for those with an affected halfsibling. In those <65 years old, shared childhood (RR: 1.41, 95% CI: 1.26-1.57) and household (RR: 2.08, 95% CI: 1.25-3.46) environments were significantly greater contributors to familial risk of CRC than genetics (RR: 0.88, 95% CI: 0.53-1.46). This large-scale Nordic population-based study of excess risk of CRC among relatives of those with CRC addresses the difficult disentangling of shared environment from genetic predisposition in the heritability of CRC. We found shared environment to be the most important contributor to CRC risk.

Increased risk of genital warts in inflammatory bowel disease: A Danish registry-based cohort study (1996-2018).

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of human papillomavirus (HPV) related cancers such as anal squamous cell carcinoma. However, risk of non-malignant HPV infection has never been systematically studied in IBD. This study aims to assess the risk of genital warts (GW) in IBD patients. METHODS: Using the Danish nationwide registries, we identified 49,163 patients with IBD between 1996 and 2018 and matched them to 491,665 individuals from the general population by age, sex, and HPV immunisation. Cumulative incidence rates for GW in IBD and non-IBD patients were calculated by age. Cox proportional regression analysis was used to calculate hazard ratios (HR) for GW in IBD compared to matched population and in Crohn's disease (CD) compared to ulcerative colitis (UC). We undertook subgroup analysis for risk of GW by sex, year of IBD diagnosis, contraceptive exposure and IBD treatment exposure. RESULTS: The fully adjusted HR for GW in IBD patients compared to the matched non-IBD population was 1.33 (95% CI: 1.19-1.49) and 1.13 (95% CI: 1.01, 1.27) in CD as compared to UC. This increased risk was particularly observed in female (HR: 1.54, 95% CI: 1.33-1.79) over male (HR: 1.14, 95% CI: 0.97-1.34) IBD patients, but was also found across all periods of diagnosis with IBD, regardless of contraceptive treatment exposure, and also seen in IBD patients who had never been exposed to immunosuppressive treatment (HR: 1.33, 95% CI: 1.19-1.49). CONCLUSION: In this nationwide, population-representative cohort study, we observed a 33% increased risk of GW in patients with IBD compared to the matched population and a 13% increased risk of GW in CD compared with UC. This risk was particularly increased in female over male IBD patients and seen independent of IBD treatment exposure.

Development of Cancer Among Patients With Pediatric-Onset Inflammatory Bowel Disease: A Meta-analysis of Population-Based Studies.

IMPORTANCE: Because the incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing, knowledge of the long-term risk of cancer in this patient population is required. OBJECTIVE: To evaluate the relative rate of cancer among patients with pediatric-onset IBD. DATA SOURCES: A comprehensive systematic search was performed of MEDLINE and Embase from the date of database inception to October 31, 2021. STUDY SELECTION: All unselected, population-based cohort studies of pediatric-onset IBD assessing the risk of cancer were included. Tertiary center referrals and insurance database studies were excluded. All articles were assessed by 2 independent reviewers. DATA EXTRACTION AND SYNTHESIS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline for data extraction and used the Newcastle-Ottawa Scale for assessment of the risk of bias and the quality of included articles. MAIN OUTCOMES AND MEASURES: A random-effects model meta-analysis was conducted of included studies using the inverse-variance method to assess the relative rate of cancer overall and by IBD subtype (Crohn disease or ulcerative colitis), sex, and thiopurine exposure among patients with pediatric-onset IBD. Pooled relative rates (pRRs) along with 95% CIs were calculated for combined studies. RESULTS: Of 4628 articles screened, 5 population-based studies from North America and Europe were eligible for inclusion. These studies comprised 19 812 individuals with pediatric-onset IBD followed up for 283 540 person-years in which 715 cases of cancer were identified. Meta-analysis of pRR estimates showed a 2.4-fold increased rate of cancer among patients with pediatric-onset IBD (pRR, 2.46; 95% CI, 2.06-2.93), seen among patients with Crohn disease (pRR, 2.03; 95% CI, 1.67-2.46) and those with ulcerative colitis (pRR, 2.61; 95% CI, 2.00-3.40). This increased rate is primarily due to an increased rate of liver (pRR, 55.45; 95% CI, 19.59-156.99), colorectal (pRR, 20.29; 95% CI, 15.90-25.90), and small bowel (pRR, 16.20; 95% CI, 3.52-74.66) cancers. The incidence rate of cancer among patients with pediatric-onset IBD was reported by 4 studies and ranged from 1.0 to 3.3 cases per 1000 person-years. CONCLUSIONS AND RELEVANCE: This meta-analysis of unselected, population-based studies showed a greater than 2-fold increased rate of cancer among patients with pediatric-onset IBD compared with the general pediatric populations, primarily owing to an increased rate of gastrointestinal cancers.

Impact of thiopurine discontinuation at anti-tumour necrosis factor initiation in inflammatory bowel disease treatment: a nationwide Danish cohort study.

BACKGROUND: Escalation to anti-tumour necrosis factor (anti-TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing thiopurine at escalation is unclear. AIM: To assess the impact of discontinuing versus continuing thiopurine therapy at anti-TNF initiation. METHODS: We used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti-TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti-TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD-related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Of the 10,352 anti-TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti-TNF. After anti-TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti-TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10-1.36), particularly for IBD-related hospitalization (aHR: 1.14; 95% CI: 1.00-1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13-1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02-1.34) and UC (aHR: 1.32; 95% CI: 1.12-1.55). CONCLUSIONS: In a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti-TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required.

Low levels of HIV test coverage in clinical settings in the U.K.: a systematic review of adherence to 2008 guidelines.

OBJECTIVES: To quantify the extent to which guideline recommendations for routine testing for HIV are adhered to outside of genitourinary medicine (GUM), sexual health (SH) and antenatal clinics. METHODS: A systematic review of published data on testing levels following publication of 2008 guidelines was undertaken. Medline, Embase and conference abstracts were searched according to a predefined protocol. We included studies reporting the number of HIV tests administered in those eligible for guideline recommended testing. We excluded reports of testing in settings with established testing surveillance (GUM/SH and antenatal clinics). A random effects meta-analysis was carried out to summarise level of HIV testing across the studies identified. RESULTS: Thirty studies were identified, most of which were retrospective studies or audits of testing practice. Results were heterogeneous. The overall pooled estimate of HIV test coverage was 27.2% (95% CI 22.4% to 32%). Test coverage was marginally higher in patients tested in settings where routine testing is recommended (29.5%) than in those with clinical indicator diseases (22.4%). Provider test offer was found to be lower (40.4%) than patient acceptance of testing (71.5%). CONCLUSIONS: Adherence to 2008 national guidelines for HIV testing in the UK is poor outside of GUM/SH and antenatal clinics. Low levels of provider test offer appear to be a major contributor to this. Failure to adhere to testing guidelines is likely to be contributing to late diagnosis with implications for poorer clinical outcomes and continued onwards transmission of HIV. Improved surveillance of HIV testing outside of specialist settings may be useful in increasing adherence testing guidelines.