Treatment outcome of tofacitinib dose reduction to 5 mg BID vs remaining on 10 mg BID in patients with Ulcerative Colitis who were in stable remission on 10 mg BID: Updated 30-month data from the double-blind, randomised RIVETING study

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. The long-term, Phase 3b/4 RIVETING study (NCT03281304) assessed the efficacy and safety of tofacitinib dose reduction from tofacitinib 10 mg twice daily (BID) maintenance therapy to 5 mg BID in patients (pts) in stable remission. 1 We present a final analysis of the RIVETING study after >=30 months of treatment. Method(s): RIVETING was a double-blind, randomised, parallelgroup study with a 42-month (M) duration. Eligible pts had received tofacitinib 10 mg BID for >=2 consecutive years in an open-label, long-term extension study (NCT01470612), had been in stable remission for >=6 months and corticosteroid-free for >=4 weeks prior to baseline. The primary efficacy endpoint was remission at M6 based on modified Mayo (mMayo) score (endoscopic and stool frequency subscores of <=1 and rectal bleeding subscore of 0).1 RIVETING was terminated (primary objective met) when all pts had passed M30 (or discontinued);some pts had already completed all visits up to M42. Here, we assess efficacy at M30 and safety throughout. Result(s): Overall, 140 pts were randomised (1:1) to tofacitinib 5 or 10 mg BID;50.0% and 62.9% were in remission based on mMayo score at M30 in the 5 and 10 mg BID dose groups, respectively, with consistent findings observed for other secondary efficacy endpoints (Table 1). At M30, observed differences for mMayo remission between tofacitinib 10 and 5 mg BID were generally greater in the subgroup with a baseline endoscopic subscore of 1 vs 0 and in the subgroup with vs without prior tumour necrosis factor inhibitor (TNFi) failure (Table 1). The percentage of pts who experienced loss of remission by M30, as estimated from Kaplan-Meier curves, was numerically higher in the 5 vs the 10 mg BID dose group (28.1%;95% confidence interval [CI], 17.68-39.49 vs 21.7%;95% CI, 12.21-32.95, respectively). Table 2 shows adverse events of special interest, by dose group. One death occurred due to fatal coronavirus disease 2019 pneumonia (10 mg BID). Conclusion(s): These long-term data showed that most pts in stable remission on tofacitinib 10 mg BID maintenance therapy maintained mMayo score remission through M30 after dose reduction to 5 mg BID. Dose group difference in remission at M30 was consistent with that at M6.1 Differences in remission between the tofacitinib 5 and 10 mg BID groups were greater in subgroups with an endoscopic subscore of 1 vs 0 and in subgroups with vs without prior TNFi failure. Overall, safety findings were consistent with tofacitinib's known safety profile;incidence of serious infections and herpes zoster was numerically higher in the tofacitinib 10 vs 5 mg BID group. (Table Presented).

The Effect of COVID-19 Pandemic in Intestinal Rehabilitation and Transplant Patients - International Multicenter Survey

Purpose: It has been proposed that patients with intestinal failure (IF) and intestine transplant (IT) are at higher risk of severe complications of COVID-19 due to weakened immunity and comorbidities. Multidisciplinary teams had to adapt their clinical approaches in order to keep these patients as safe as possible during the pandemic. Data is lacking. Method(s): Retrospective, observational, multicenter study performed with 3 surveys to assess COVID-19 practice changes in IF and IT patients. Result(s): 17 centers were included in the analysis;six had a 3 (+/- 4) months moratorium on performing transplant. Nine delayed their routine follow up including "protocol" biopsies. Nine reported decrease in new referrals. Sixteen incorporated telemedicine. Two reported rehabilitation services (home health, PN deliveries) being affected. In the first survey, 10 centers (59%) reported having IF and IT patients with COVID-19. In the other 2 surveys, a total of 25 IF and IT patients were reported positive for COVID-19. Of the 11 IF patients, 8 were male;7 were adults, with a mean age of 60 (+/- 8) years. Nine of them were symptomatic at presentation, with the most prevalent symptoms being fever/chills, cough and sore throat;hospitalization was required in 45.5%, all patients survived. A total of 14 IT patients were positive;8 were female;all of them were adults, mean age: 47 (+/- 16) years. All of them were symptomatic at presentation, with the most prevalent symptoms being fever/chills, dyspnea and cough. Hospitalization was required in 50%. Immunosuppression was discontinued in 1 patient, decreased in 5 (all on tacrolimus), and left unchanged in 8 cases;3 patients (21%) died. Conclusion(s): Many aspects of healthcare have been impacted by the COVID-19 pandemic. Centers adapted to new paradigms in patient care. Despite the availability of telemedicine, hospitals that treat IF and IT patients have found difficulties to sustain an appropriate home care regimen and referrals. IF patients did not have increased mortality, but IT recipients did, with similar results to those reported for other solid organs.

Consumer preferences for grocery purchasing during the COVID-19 pandemic: a quantile regression approach

Purpose The objective is to determine if consumer preferences for grocery purchasing are impacted by the severity of the COVID-19 pandemic and whether these preferences differ by demographic and psychographic characteristics. Design/methodology/approach The authors conduct an online discrete choice experiment (DCE) with 900 U.S. consumers to assess grocery shopping preferences under various scenarios of the COVID-19 pandemic (i.e. decreasing, constant and increasing cases). The attribute of interest is the purchasing method (i.e. in-store purchase, in-store pickup, curbside pickup and home delivery) with minimum order requirements, time windows and fees as secondary attributes. Heterogeneity in individual-level willingness-to-pay (WTP) estimates for the main attribute is analyzed by means of mixed logit and quantile regression techniques. Findings The mixed logit model reveals heterogeneity in WTP estimates for grocery purchasing methods across participants. According to estimates from quantile regressions, the heterogeneity is partly explained by the severity of the COVID-19 pandemic. For example, the home delivery purchasing method is less preferred when the number of cases is decreasing. The results also show that consumer preferences for grocery shopping methods are affected more by psychographic characteristics than demographic characteristics. Consumers who comply with COVID-19 directives (e.g. wear face coverings) have stronger preferences for curbside pickup and home delivery, particularly at the tails of the WTP distributions. Originality/value Although there is much data on food consumer behavior during the COVID-19 pandemic at the aggregate level, there are few analyses of grocery shopping preferences at the individual level. The study represents a first attempt to relate individuals' demographic and psychographic characteristics to their grocery shopping preferences during the COVID-19 pandemic, thus yielding numerous recommendations in terms of consumer segmentation.

Peri-COVID trends on the intestinal transplant waiting list

Purpose: We aim to describe the trends in intestinal and multivisceral transplant waiting list activity and outcomes before and after the COVID-19 pandemic. Methods: We used the cohort of intestinal and multivisceral transplant candidates who were on the waiting list November 1, 2020 - June 12, 2020 as recorded in the UNOS STAR files pulled on June 12, 2020. March 1, 2020 was considered “post- COVID.” We used the INTESTINE-WLHISTORY-DATA file to evaluate the frequency of waitlist additions, modifications, and removals over time. Monthly regional Expected events were calculated using the average monthly number of events February 2019-February 2020, and compared to monthly regional Observed events during March 2020-May 2020 Results: In the four months pre-COVID, 193 changes were made to the intestine waiting list, compared with 257 post-COVID. One center reported a dramatic increase in waiting list activity in May 2020, with high activation & inactivation of candidates. All other centers combined exhibited a decrease in intestinal transplant waitlist additions and activations post-COVID. Observed:Expected ratios (O:E) for waitlist activity and transplants stratified by intestine-only and multivisceral candidates are shown in Figure 1. Regions 6 and 7 had no recorded multivisceral waiting list additions, removals, or modifications after March 1, 2020. After March 1, 2020, most regions performed fewer transplants, with a minority increasing their monthly transplant volume. National monthly transplant rates remained stable. Figure 2. There were very few waiting list deaths, with only two recorded post-COVID. Conclusions: Though most regions reduced intestinal and multivisceral transplant volumes after March 1, 2020, national transplant rates remained stable demonstrating significant regional variation in COVID-19 effect on practice.

The effect of the COVID-19 pandemic in intestinal rehabilitation and transplant patients, initial results of an international survey

Introduction: On January 30, 2020 the World Health Organization (WHO) declared the 2019-CoV outbreak in China as a global public health emergency and subsequently, a pandemic on March 11th. It was considered that intestinal failure and intestinal transplant patients might have a higher risk of severe complications from the COVID-19 disease, multidisciplinary intestinal failure teams had to adapt their clinical approaches in order to keep this vulnerable group of patients as safe as possible during the pandemic;but data was lacking. Therefore, in order to improve our knowledge, we designed a voluntary, international survey aiming to address the impact of the COVID-19 disease in intestinal failure and transplant patients worldwide. Patient and Methods: A retrospective, observational, multicenter survey was sent to all centers registered at the Intestinal Rehabilitation and Transplant Association (IRTA). The survey contained three modules: the 1st one consisted of 14 questions about the hospital's activity during the COVID-19 pandemic. The 2nd one, contained 43 questions, was about intestinal failure patient management and outcome and the 3rd one (52 questions) focused on intestinal transplant patients. We used the Google Form platform. We aim to present the preliminary results of the first module. Statistical analysis was performed with the IBM SPSS Statistic version 25.0® program. Results: 13/42 (41%) centers responded;including centers from France, Netherlands, Italy, United States, UK, Sweden, Germany and Argentina. Only 2 centers reported moratorium on intestinal (IT) or multivisceral transplant (MVT), with a mean of 3 months (±4) [Table 1]. Since the pandemic started, 2 institutions reported 4 patients with intestinal rehabilitation or on TPN diagnosed with COVID-19 while 7 centers hospitals claimed to have had 9 patients post-IT/MTV affected by the disease. While 7 centers had their routine follow up and 'protocol biopsies' in the post-IT/MTV affected, none reported higher rates of rejection or complications. At the same time, 8 centers (77%) were affected by a mean of 15% decrease in referrals for new evaluations of intestinal failure or transplantation (compared to 2019) [Figure 1]. All centers adapted to utilizing telemedicine to follow up on IT/MVT patients Conclusions: Many aspects of healthcare have been impacted by the COVID-19 pandemic. The survey showed that the number of affected patients has been lower than expected, the reduced number of centers required transient moratorium of their activity, but a secondary observation was that despite the availability of telemedicine, and probably related to the lockdown, there has been a significant reduction in the referrals for evaluation of intestinal failure and transplant patients, that may have the deleterious effect of the delay of treatment in health care system.

Ivermectin reduces in vivo coronavirus infection in a mouse experimental model.

The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.