Highlights of the drug-induced liver injury literature for 2021.

INTRODUCTION: In 2021, over 3,000 articles on Drug-Induced Liver Injury (DILI) were published, nearly doubling the annual number compared to 2011. This review selected DILI articles from 2021 we felt held the greatest interest and clinical relevance. AREAS COVERED: A literature search was conducted using PubMed between 1 March 2021 and 28 February 2022. 86 articles were included. This review discusses new and established cases of hepatotoxins, including new FDA approvals and COVID-19 therapeutics. Developments in biomarkers and causality assessment methods are discussed. Updates from registries are also explored. EXPERT OPINION: DILI diagnosis and prognostication remain challenging. Roussel Uclaf Causality Assessment Method (RUCAM) is the best option for determining causality and has been increasingly accepted by clinicians. Revised Electronic Causality Assessment Method (RECAM) may be more user-friendly and accurate but requires further validation. Quantitative systems pharmacology methods, such as DILIsym, are increasingly used to predict hepatotoxicity. Oncotherapeutic agents represent many newly approved and described causes of DILI. Such hepatotoxicity is deemed acceptable relative to the benefit these drugs offer. Drugs developed for non-life-threatening disorders may not show a favorable benefit-to-risk ratio and will be more difficult to approve. As the COVID-19 landscape evolves, its effect on DILI deserves further investigation.

Use of standard, contact, and droplet precautions with eye protection for the prevention of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission among home healthcare personnel in hospice and home healthcare settings-King and Snohomish counties, Washington, February-October 2020.

Among EvergreenHealth Home Care Service professionals, no coronavirus disease 2019 (COVID-19) cases were reported when they were instructed to use standard, contact, and droplet precautions with eye protection while providing home health care to patients diagnosed with laboratory-confirmed severe acute respiratory coronavirus virus 2 (SARS-CoV-2). These precautions might provide some level of protection against coronavirus disease 2019 (COVID-19) among home healthcare personnel.

Vaccine Effectiveness against SARS-CoV-2 Variant P.1 in Nursing-Facility Residents, Washington, USA, April 2021.

A SARS-CoV-2 P.1 (Gamma) variant outbreak occurred at a skilled nursing facility in Washington, USA, in April 2021. Effectiveness of 2 doses of mRNA vaccines against P.1 infection among residents in this outbreak was 75.0% (95% CI 44.5%-88.7%), similar to effectiveness for other pre-Delta variants among long-term care residents.

A novel digital rectoscope for the triage of lower gastrointestinal symptoms in primary care: a prospective multicentre feasibility study.

BACKGROUND: Access to community rectoscopy might help to ease the burden on hospital services and reduce costs for the NHS. To assess this, a prospective multicentre observational phase I feasibility study of a novel digital rectoscope and telestration software for the triage of lower gastrointestinal (GI) symptoms was undertaken. AIM: To determine if digital rectoscopy is feasible, acceptable, and clinically safe. DESIGN & SETTING: Evaluation of clinician case reports and patient questionnaires from patients recruited from five primary care centres. METHOD: Adults meeting 2-week wait (2WW) criteria for suspected lower GI cancer, suspected new diagnosis, or flare-up of inflammatory bowel disease (IBD) were enrolled. Examinations were performed by primary care practitioners using the LumenEye rectoscope. The CHiP platform allowed immediate remote review by secondary care. A prospective analysis was performed of patient and clinician experiences, diagnostic accuracy, and cost. RESULTS: A total of 114 patients were recruited and 110 underwent the procedure (46 [42%] females and 64 [58%] males). No serious adverse events were reported. Eighty-two (74.5%) patients reported that examination was more comfortable than expected, while 104 (94.5%) felt the intervention was most convenient if delivered in the community. Clinicians were confident of their assessment in 100 (87.7%) examinations. Forty-eight (42.1%) patients subsequently underwent colonoscopy, flexible sigmoidoscopy, or computed tomography virtual colonoscopy (CTVC). The overall sensitivity and specificity of LumenEye in identifying rectal pathology was 90.0% and 88.9%. It was 100% and 100% for cancer, and 83.3% and 97.8% for polyps. Following LumenEye examination, 19 (17.3%) patients were discharged, with projected savings of 11 305 GBP. CONCLUSION: Digital rectoscopy in primary care is safe, acceptable, and can reduce referrals. A phase III randomised controlled trial is indicated to define its utility in reducing the burden on hospital diagnostic services.

Risks of Development of COVID-19 Among Patients With Inflammatory Bowel Disease: A Comparative Assessment of Risk Factors for Incident Infection.

Background: Patients with inflammatory bowel disease (IBD) may be at risk for development of COVID-19 infection due to innate immune dysfunction and/or immunosuppressive medication use. Methods: In a prospective cohort of adult IBD patients, we captured data on clinical risk factors and IBD medication utilization. The outcome of interest was development of patient-reported laboratory confirmed COVID-19. We calculated incidence rate and performed bivariate analyses to describe the effects of risk factors (age, immunosuppression use, obesity, and race) on development of COVID-19. We utilized logistic regression models to determine the independent risks associated with each factor. Results: A total of 3953 patients with IBD were followed for a mean duration of 212 days (SD 157). A total of 103 individuals developed COVID-19 during follow-up (2.6%, rate of 45 per 1000 person-years). Severity of infection was generally mild. Clinical characteristics were similar among those who developed COVID-19 as compared to not. African American race was associated with incident COVID-19 infection (OR 3.37, 95% CI 1.18-9.59). Immunosuppression use was not associated with development of COVID-19 (OR 1.19, 95% CI 0.72-1.75), nor was age (OR 1.00, 95% CI 0.99-1.02), nor obesity (OR 1.01, 95% CI 0.61-1.66). Conclusions: Immunosuppression use did not increase the risk of development of COVID-19. Therapeutic management of IBD should not be altered to prevent a risk of developing COVID-19.

The Multiple Waves of COVID-19 in Patients With Inflammatory Bowel Disease: A Temporal Trend Analysis.

BACKGROUND: Cases of coronavirus disease 2019 (COVID-19) have emerged in discrete waves. We explored temporal trends in the reporting of COVID-19 in inflammatory bowel disease (IBD) patients. METHODS: The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry of IBD patients diagnosed with COVID-19. The average percent changes (APCs) were calculated in weekly reported cases of COVID-19 during the periods of March 22 to September 12, September 13 to December 12, 2020, and December 13 to July 31, 2021. RESULTS: Across 73 countries, 6404 cases of COVID-19 were reported in IBD patients. COVID-19 reporting decreased globally by 4.2% per week (95% CI, -5.3% to -3.0%) from March 22 to September 12, 2020, then climbed by 10.2% per week (95% CI, 8.1%-12.3%) from September 13 to December 12, 2020, and then declined by 6.3% per week (95% CI, -7.8% to -4.7%). In the fall of 2020, weekly reporting climbed in North America (APC, 11.3%; 95% CI, 8.8-13.8) and Europe (APC, 17.7%; 95% CI, 12.1%-23.5%), whereas reporting was stable in Asia (APC, -8.1%; 95% CI, -15.6-0.1). From December 13, 2020, to July 31, 2021, reporting of COVID-19 in those with IBD declined in North America (APC, -8.5%; 95% CI, -10.2 to -6.7) and Europe (APC, -5.4%; 95% CI, -7.2 to -3.6) and was stable in Latin America (APC, -1.5%; 95% CI, -3.5% to 0.6%). CONCLUSIONS: Temporal trends in reporting of COVID-19 in those with IBD are consistent with the epidemiological patterns COVID-19 globally.

Drug-Induced Liver Injury: Highlights and Controversies in the Recent Literature.

Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice. Several new drugs were approved by the US Food and Drug Administration including a number of drugs implicated in causing DILI, particularly among the chemotherapeutic classes. The COVID-19 pandemic was also a major focus of attention in 2020 and we discuss some of the notable aspects of COVID-19-related liver injury and its implications for diagnosing DILI. Updates in diagnostic and causality assessments related to DILI such as the Roussel Uclaf Causality Assessment Method are included, mindful that there is still no single biomarker or diagnostic tool to unequivocally diagnose DILI. Glutamate dehydrogenase received renewed attention as being more specific than alanine aminotransferase. There were a few new reports of previously unrecognized hepatotoxins, including immune modulators and novel gene therapy drugs that we highlight. Updates and new developments of previously described hepatotoxins, such as immune checkpoint inhibitors and anti-tuberculosis drugs are reviewed. Finally, novel technologies such as organoid culture systems to better predict DILI preclinically may be coming of age and determinants of hepatocyte loss, such as calculating PALT are poised to improve our current means of estimating DILI severity and the risk of acute liver failure.

Penetration and impact of COVID-19 in long term care facilities in England: population surveillance study.

BACKGROUND: Long-term care facilities (LTCF) worldwide have suffered high rates of COVID-19, reflecting the vulnerability of the persons who live there and the institutional nature of care delivered. This study describes the impact of the pandemic on incidences and deaths in LTCF across England. METHODS: Laboratory-confirmed SARS-CoV-2 cases in England, notified to Public Health England from 01 Jan to 25 Dec 2020, were address-matched to an Ordnance Survey reference database to identify residential property classifications. Data were analysed to characterize cases and identify clusters. Associated deaths were defined as death within 60 days of diagnosis or certified as cause of death. RESULTS: Of 1 936 315 COVID-19 cases, 81 275 (4.2%) and 10 050 (0.52%) were identified as resident or staff in an LTCF, respectively, with 20 544 associated deaths in residents, accounting for 31.3% of all COVID-19 deaths. Cases were identified in 69.5% of all LTCFs in England, with 33.1% experiencing multiple outbreaks. Multivariable analysis showed a 67% increased odds of death in residents [adjusted odds ratio (aOR): 1.67, 95% confidence interval (CI): 1.63-1.72], compared with those not residing in LTCFs. A total of 10 321 outbreaks were identified at these facilities, of which 8.2% identified the first case as a staff member. CONCLUSIONS: Over two-thirds of LTCFs have experienced large and widespread outbreaks of COVID-19, and just under one-third of all COVID-19 deaths occurring in this setting in spite of early policies. A key implication of our findings is upsurges in community incidences seemingly leading to increased outbreaks in LTCFs; thus, identifying and shielding residents from key sources of infection are vital to reduce the number of future outbreaks.

Epidemiology of COVID-19 in Prisons, England, 2020.

Using laboratory data and a novel address matching methodology, we identified 734 cases of coronavirus disease in 88 prisons in England during March 16-October 12, 2020. An additional 412 cases were identified in prison staff and household members. We identified 84 prison outbreaks involving 86% of all prison-associated cases.

COVID-19 Outcomes Among Racial and Ethnic Minority Individuals With Inflammatory Bowel Disease in the United States.

The coronavirus disease 2019 (COVID-19) has affected more than 29 million people and led to more than 542,000 deaths in the United States.1 Older age, comorbidities, and racial and ethnic minority status are associated with severe COVID-19.2 Among patients with inflammatory bowel disease (IBD), racial and ethnic minorities have worse outcomes, mediated in part by inequitable health care access.3 Racial and ethnic minority patients with IBD and COVID-19 may be an especially vulnerable population. The purpose of this study was to evaluate racial and ethnic disparities in COVID-19 outcomes among IBD patients and the impact of non-IBD comorbidities on observed disparities.

Risk factors for SARS-CoV-2 infection and course of COVID-19 disease in patients with IBD in the Veterans Affair Healthcare System.

OBJECTIVE: Our aim was to explore the risk of infection with all classes of inflammatory bowel disease (IBD) medications and the impact of these medications on the disease course in a nationwide cohort of patients with IBD. DESIGN: This was a retrospective national cohort study of patients with IBD in the Veterans Affairs Healthcare System. We categorised IBD medication use immediately prior to the COVID-19 pandemic and used survival analysis methods to study associations with SARS-CoV-2 infection, as well as a combined secondary outcome of COVID-19 hospitalisation or COVID-19-related mortality. RESULTS: The analytical cohort of 30 911 patients was primarily male (90.9%), white (78.6%) and with ulcerative colitis (58.8%). Over a median follow-up of 10.7 months, 649 patients (2.1%) were diagnosed with SARS-CoV-2 infection and 149 (0.5%) met the combined secondary outcome. In adjusted models, vedolizumab (VDZ) use was significantly associated with infection relative to mesalazine alone (HR 1.70, 95% CI 1.16 to 2.48, p=0.006). Patients on no IBD medications had increased risk of the combined secondary outcome relative to mesalazine alone (sub-HR 1.64, 95% CI 1.12 to 2.42, p=0.01), however, no other IBD medication categories were significantly associated with this outcome, relative to mesalazine alone (each p>0.05). Corticosteroid use was independently associated with both SARS-CoV-2 infection (HR 1.60, 95% CI 1.23 to 2.09, p=0.001) and the combined secondary outcome (sub-HR 1.90, 95% CI 1.14 to 3.17, p=0.01). CONCLUSION: VDZ and corticosteroid were associated with an increased risk of SARS-CoV-2 infection. Except for corticosteroids no medications including mesalazine were associated with an increased risk of severe COVID-19.

The importance of coaching and learning agility in a high change world

In a 2017 survey, 62 per cent of organisations were facing significant amounts of change. This level will clearly have risen since Covid-19. Psychologists have an understanding about some of the characteristics that allow leaders to remain resilient and engaged, even in the face of substantial change. This study takes the next step. It examined the characteristics of leaders that allow them to provide their teams with a positive work environment in order to keep them engaged. Different work environments, including those involving significant change, were studied. A number of traits and learning agilities were identified that were important. However, it emerged that using coaching as a leadership style is one of the most effective things a leader can do to build team commitment. [ABSTRACT FROM AUTHOR] Copyright of Assessment & Development Matters is the property of British Psychological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Community prevalence of SARS-CoV-2 in England from April to November, 2020: results from the ONS Coronavirus Infection Survey.

BACKGROUND: Decisions about the continued need for control measures to contain the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on accurate and up-to-date information about the number of people testing positive for SARS-CoV-2 and risk factors for testing positive. Existing surveillance systems are generally not based on population samples and are not longitudinal in design. METHODS: Samples were collected from individuals aged 2 years and older living in private households in England that were randomly selected from address lists and previous Office for National Statistics surveys in repeated cross-sectional household surveys with additional serial sampling and longitudinal follow-up. Participants completed a questionnaire and did nose and throat self-swabs. The percentage of individuals testing positive for SARS-CoV-2 RNA was estimated over time by use of dynamic multilevel regression and poststratification, to account for potential residual non-representativeness. Potential changes in risk factors for testing positive over time were also assessed. The study is registered with the ISRCTN Registry, ISRCTN21086382. FINDINGS: Between April 26 and Nov 1, 2020, results were available from 1 191 170 samples from 280 327 individuals; 5231 samples were positive overall, from 3923 individuals. The percentage of people testing positive for SARS-CoV-2 changed substantially over time, with an initial decrease between April 26 and June 28, 2020, from 0·40% (95% credible interval 0·29-0·54) to 0·06% (0·04-0·07), followed by low levels during July and August, 2020, before substantial increases at the end of August, 2020, with percentages testing positive above 1% from the end of October, 2020. Having a patient-facing role and working outside your home were important risk factors for testing positive for SARS-CoV-2 at the end of the first wave (April 26 to June 28, 2020), but not in the second wave (from the end of August to Nov 1, 2020). Age (young adults, particularly those aged 17-24 years) was an important initial driver of increased positivity rates in the second wave. For example, the estimated percentage of individuals testing positive was more than six times higher in those aged 17-24 years than in those aged 70 years or older at the end of September, 2020. A substantial proportion of infections were in individuals not reporting symptoms around their positive test (45-68%, dependent on calendar time. INTERPRETATION: Important risk factors for testing positive for SARS-CoV-2 varied substantially between the part of the first wave that was captured by the study (April to June, 2020) and the first part of the second wave of increased positivity rates (end of August to Nov 1, 2020), and a substantial proportion of infections were in individuals not reporting symptoms, indicating that continued monitoring for SARS-CoV-2 in the community will be important for managing the COVID-19 pandemic moving forwards. FUNDING: Department of Health and Social Care.

The Need for Antiviral Drugs for Pandemic Coronaviruses From a Global Health Perspective.

Respiratory failure due to SARS-CoV-2 has caused widespread mortality, creating an urgent need for effective treatments and a long-term need for antivirals for future emergent coronaviruses. Pharmacotherapy for respiratory viruses has largely been unsuccessful with the exception of early treatment of influenza viruses, which shortens symptom duration and prevents infection in close contacts. Under the rapidly evolving circumstances of the COVID-19 pandemic, most clinical trials of experimental treatments in the United States have focused on later stages of the disease process. Worldwide, the clinical studies of the most impactful drugs, remdesivir and dexamethasone in ACTT-1, RECOVERY, and Solidarity, have studied hospitalized patients. Less than half of clinical trials in the U.S. have investigated oral agents, and the majority have taken place in hospitals at a disease stage where the viral load is already decreasing. The limited success of treatments for respiratory viruses and the viral dynamics of COVID-19 suggest that an antiviral therapy with the greatest impact against pandemic coronaviruses would be orally administered, well-tolerated, target a highly conserved viral protein or host-coronavirus interaction and could be used effectively throughout the world, including resource-poor settings. We examine the treatment of respiratory viral infections and current clinical trials for COVID-19 to provide a framework for effective antiviral therapy and prevention of future emergent coronaviruses and call attention to the need for continued preclinical drug discovery.

An ecological study to evaluate the association of Bacillus Calmette-Guerin (BCG) vaccination on cases of SARS-CoV2 infection and mortality from COVID-19.

As the SARS-CoV2 pandemic has progressed, there have been marked geographical differences in the pace and extent of its spread. We evaluated the association of BCG vaccination on morbidity and mortality of SARS-CoV2, adjusted for country-specific responses to the epidemic, demographics and health. SARS-CoV2 cases and deaths as reported by 31 May 2020 in the World Health Organization situation reports were used. Countries with at least 28 days following the first 100 cases, and available information on BCG were included. We used log-linear regression models to explore associations of cases and deaths with the BCG vaccination policy in each country, adjusted for population size, gross domestic product, proportion aged over 65 years, stringency level measures, testing levels, smoking proportion, and the time difference from date of reporting the 100th case to 31 May 2020. We further looked at the association that might have been found if the analyses were done at earlier time points. The study included 97 countries with 73 having a policy of current BCG vaccination, 13 having previously had BCG vaccination, and 11 having never had BCG vaccination. In a log-linear regression model there was no effect of country-level BCG status on SARS-CoV2 cases or deaths. Univariable log-linear regression models showed a trend towards a weakening of the association over time. We found no statistical evidence for an association between BCG vaccination policy and either SARS-CoV2 morbidity or mortality. We urge countries to rather consider alternative tools with evidence supporting their effectiveness for controlling SARS-CoV2 morbidity and mortality.

The COVID-19 pandemic: a target for surfactant therapy?

INTRODUCTION: The dramatic impact of COVID-19 on humans worldwide has initiated an extraordinary search for effective treatment approaches. One of these is the administration of exogenous surfactant, which is being tested in ongoing clinical trials. AREAS COVERED: Exogenous surfactant is a life-saving treatment for premature infants with neonatal respiratory distress syndrome. This treatment has also been tested for acute respiratory distress syndrome (ARDS) with limited success possibly due to the complexity of that syndrome. The 60-year history of successes and failures associated with surfactant therapy distinguishes it from many other treatments currently being tested for COVID-19 and provides the opportunity to discuss the factors that may influence the success of this therapy. EXPERT OPINION: Clinical data provide a strong rationale for using exogenous surfactant in COVID-19 patients. Success of this therapy may be influenced by the mechanical ventilation strategy, the timing of treatment, the doses delivered, the method of delivery and the preparations utilized. In addition, future development of enhanced preparations may improve this treatment approach. Overall, results from ongoing trials may not only provide data to indicate if this therapy is effective for COVID-19 patients, but also lead to further scientific understanding and improved treatment strategies.

Physician Practice Patterns in Holding Inflammatory Bowel Disease Medications due to COVID-19, in the SECURE-IBD Registry.

BACKGROUND: We aimed to describe physician practice patterns in holding or continuing IBD therapy in the setting of COVID-19 infection, using the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease [SECURE-IBD] registry. METHODS: IBD medications that were stopped due to COVID-19 were recorded in the SECURE-IBD registry in addition to demographic and clinical data. We conducted descriptive analyses to understand characteristics associated with stopping IBD medications in response to active COVID-19 infection. RESULTS: Of 1499 patients, IBD medications were stopped in 518 [34.6%] patients. On bivariate and multivariable analyses, a diagnosis of ulcerative colitis or IBD-unspecified was associated with a lower odds of stopping medication compared with Crohn's disease (adjusted odds ratio [aOR] 0.6, 95% confidence interval [CI] 0.48, 0.75). When evaluating specific medications, 5-aminosalicylic acid was more likely to be continued [p <0.001] whereas anti-tumour necrosis factor therapy and immunomodulator therapy were more likely to be stopped [global p <0.001]. Other demographic and clinical characteristics did not affect prescription patterns. CONCLUSIONS: IBD medications other than immunomodulators were continued in the majority of IBD patients with COVID-19, in the international SECURE-IBD registry. Future studies are needed to understand the impact of stopping or continuing IBD medications on IBD- and COVID-19 related outcomes.

Effect of IBD medications on COVID-19 outcomes: results from an international registry.

OBJECTIVE: We sought to evaluate COVID-19 clinical course in patients with IBD treated with different medication classes and combinations. DESIGN: Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of IBD patients with confirmed COVID-19. We used multivariable regression with a generalised estimating equation accounting for country as a random effect to analyse the association of different medication classes with severe COVID-19, defined as intensive care unit admission, ventilator use and/or death. RESULTS: 1439 cases from 47 countries were included (mean age 44.1 years, 51.4% men) of whom 112 patients (7.8%) had severe COVID-19. Compared with tumour necrosis factor (TNF) antagonist monotherapy, thiopurine monotherapy (adjusted OR (aOR) 4.08, 95% CI 1.73 to 9.61) and combination therapy with TNF antagonist and thiopurine (aOR 4.01, 95% CI 1.65 to 9.78) were associated with an increased risk of severe COVID-19. Any mesalamine/sulfasalazine compared with no mesalamine/sulfasalazine use was associated with an increased risk (aOR 1.70, 95% CI 1.26 to 2.29). This risk estimate increased when using TNF antagonist monotherapy as a reference group (aOR 3.52, 95% CI 1.93 to 6.45). Interleukin-12/23 and integrin antagonists were not associated with significantly different risk than TNF antagonist monotherapy (aOR 0.98, 95% CI 0.12 to 8.06 and aOR 2.42, 95% CI 0.59 to 9.96, respectively). CONCLUSION: Combination therapy and thiopurines may be associated with an increased risk of severe COVID-19. No significant differences were observed when comparing classes of biologicals. These findings warrant confirmation in large population-based cohorts.MKH should be changed to MDK for co-last author line.