ABSTRACT
COVID-19 lockdowns accelerated the take up of video calls and other digital communication between people in prison and the outside world. This has altered relationships with families and practice within rehabilitative and reintegration services. Little work has discussed the significance of these changes or articulated a normative agenda for shaping changes in future. This article aims to identify strategies that might help reintegration services and justice system agencies maximise the benefits and minimise the harms from information communication technology (ICT) use between people in prison and their families and services. Drawing from empirical literature, practical insights from service delivery and theoretical insights from assemblage theory and carceral geography, this article proposes three strategies: design spatial, scheduling and security measures to minimise stigma and disruption;actively support ICT users to equitably access the potential of ICT systems;and develop program practices in parallel with the evolutions of the technology they employ. Each of these strategies is set out with sub-components and suggestions for further research.
ABSTRACT
Background: Anti-tumour necrosis factor drugs such as infliximab are associated with attenuated antibody responses after COVID-19 vaccination It is unknown how infliximab impacts vaccine-induced serological responses against highly transmissible Omicron variants, which possess the ability to evade host immunity and are now the dominating variants causing current waves of infection Methods: In this prospective, multicentre, observational cohort study we investigated neutralising antibody responses against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants after three doses of COVID-19 vaccination in 1288 patients with IBD without prior COVID-19 infection, who were established on either infliximab (n=871) or vedolizumab (n=417). Cox proportional hazards models were constructed to investigate the risk of breakthrough infection in relation to neutralising antibody titres Results: Following three doses of COVID-19 vaccine, neutralising titre NT50 (half-inhibitory neutralising titre) was significantly diminished in patients treated with infliximab as compared to patients treated with vedolizumab, against wild-type, BA.1 and BA.4/5 variants (Fig 1). Patients with Crohn's disease showed lower antibody NT50 compared to patients with ulcerative colitis against wild-type strain and BA.4/5 (Fig 2). Older age and thiopurine were independently associated with lower NT50 against wild-type strain and BA.4/5 (Fig 2). Non-white ethnicity was associated with higher NT50 compared to white ethnicity against wild-type strain, BA.1 and BA.4/5 (Fig 2). Breakthrough infection was significantly more frequent in patients treated with infliximab compared to patients treated with vedolizumab (Fig 3). Cox proportional hazards models of time to breakthrough infection after the third dose showed infliximab treatment to be associated with a higher hazard risk (HR) of 1.71 (95% CI [1.08 to 2.71], p=0.022) compared to vedolizumab (Fig 4). Higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and a longer time to breakthrough infection (HR 0.87 [0.79 to 0.95] p=0.0028) (Fig 4) Conclusion(s): Following a third COVID-19 vaccine dose, patients established on infliximab treatment have significantly lower neutralising titres against SARS-CoV-2, which were especially low against Omicron variants. Increased breakthrough infection in infliximab recipients was associated with lower neutralising antibody titres against BA.4/5. These data underline the importance of continued COVID-19 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy may be reduced.
ABSTRACT
Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .
ABSTRACT
Background: Fatigue, pain and faecal incontinence are common in people with IBD. However, little is known about co-existence of these multiple symptoms, how they inter-relate and whether people want help for these symptoms. In qualitative interviews, patients have reported that these symptoms are often ignored in clinical consultations where the focus is on inflammation, but that they are very bothered by these symptoms, even when disease is apparently in remission The aim of this study was to determine the presence and relationship between fatigue, pain and incontinence in people with inflammatory bowel disease, and desire for intervention for these symptoms Methods: A purpose-designed survey (online or postal), incorporating validated tools and demographic details, was sent to unselected UK clinic and UK IBD-BioResource adult patients. When the covid-19 pandemic halted clinic recruitment, additional self-selected UK recruits were solicited via social media. Using the validated PROMIS tools the following definitions were used for presence of symptoms: Fatigue: PROMIS fatigue T-score of 60 or more;pain: PROMIS pain intensity T-score of 60 or more;PROMIS bowel incontinence: Raw score of 50 or more. Participants also reported disease activity using the relevant PRO-2 score, IBD-Control, anxiety (GAD-7), depression (PHQ-9) and quality of life (EQ-5D-5L) which will all be reported elsewhere Results: A total of 8486 useable responses were received (7716 online 770 postal). 4176 reported Crohn's disease, 4255 had ulcerative colitis or other form of IBD. There were 3281 men and 4883 women. Median age was 51 years (range 18 - 92). 2550 (30%) reported fatigue 1766 (21%) pain and 4565 (54%) faecal incontinence according to the above definitions;925 (10.9%) reported having all three symptoms Demographics by symptom are shown in Table 1. Table 2 reports those participants indicating the presence of each symptom and each combination of symptoms. Table 3 shows a summary of self-defined severity and impact of symptoms (scoring scale 0-10 for both severity and impact of each symptom). Participants scored severity and impact a mean between 3.3 and 4.8, with a wide variation. 56% of all respondents (not just those with symptoms) "definitely" wanted help for fatigue;42% wanted help for pain;53% wanted help for incontinence. 29% reported "definitely" wanting help for all three symptoms (Table 4) Conclusion(s): This study confirms that fatigue, pain and urgency are common in IBD and for the first time reports the co-existence and unmet need for help with these symptoms.
ABSTRACT
Purpose: In this study, the authors investigated ways to cultivate resilience through a social justice lens among ethnic minorities against COVID-19 in Hong Kong. Design/methodology/approach: A qualitative (case study) methodology was adopted to interview 15 social service providers from diverse ethnic backgrounds serving disadvantaged ethnic minority groups (South and Southeast Asian groups from low-income households, foreign domestic workers and asylum seekers/refugees). Findings: Two major protective factors were identified, contributing to the development of resilience among diverse ethnic groups: (1) individual-based resilience (including being optimistic) and (2) socio-environmental factors (including ongoing support from strong family, peer and religious settings' support, consulates' support, on-going material and nonmaterial donations, support of young volunteers and importance of online connection and communication) using the integration of resilience and social justice frameworks. Originality/value: This study showed that the protective factors were found to dynamically interact with each other and the environment. The present study recommends additional culturally sensitive service and policy implications for preventing the long-term impact of mass crises among Hong Kong's marginalized minorities. © 2023, Emerald Publishing Limited.
ABSTRACT
Background: Systemic AL amyloidosis is an incurable relapsing plasma cell disorder. Despite therapeutic advances, there are no approved treatments for relapse disease. Treatment is often challenging due to underlying organ dysfunction. Belantamab mafodotin is an antibody-drug conjugate targeting B-cell maturation antigen with approval for relapsed refractory myeloma. In multiply pre-treated myeloma, the DREAMM-2 phase II trial showed an overall response rate of 32% for those with 2.5 mg/kg dose administered every three weeks with 2/3rd patients reporting keratopathy. A small case series of 6 patients with relapsed AL amyloidosis (Zhang et al , ASH 2021) was recently reported and a phase 2 trial is recruiting for patients with refractory amyloidosis (NCT04617925). Aims: We report our initial results using Belantamab monotherapy for the treatment of patients with AL amyloidosis with relapsed disease. Methods: Data for consecutive patients who were administered Belantamab at a specialist referral centre, National Amyloidosis Centre, University College London, was analysed. Results: Eleven patients were included 8 male, 3 female. Median age at Belantamab initiation was 65 (range 42-74) years. Eight patients had λ AL-type and three κ AL-type. At diagnosis, median involved free light-chain concentration was 534 (range 73-7181) mg/l. A median of two organs involved at baseline (range 1-3): 4 had cardiac involvement (half Mayo stage 2;half Mayo stage 3a) and 8 had renal involvement. The median prior lines of therapy was 3 (range 2-5) with all exposed to prior immunomodulatory drugs, proteasome inhibitors and 73% to anti-CD38 antibody treatments. Thirty-six percent had relapsed after melphalan-conditioned autologous stem cell transplantation. A median of 3 cycles of belantamab were delivered (range 1-8). The most frequent adverse event was ocular toxicity which was experienced in 8 patients (grade 1-3), necessitating dose modification of the three-weekly schedule. One patient developed transient grade 1 dyspnoea and liver dysfunction. No patients developed cytopenias, unlike previous reports (Zhang et al , 2021), nor infections beyond COVID (2 patients mild with no hospital admissions). The majority of the cohort required dose reduction either at initiation (patient 4, due to end stage renal failure;patient 11, post-renal transplant) or during therapy (n=5;three to 1.9mg/kg, two to 1.25mg/kg) due to ocular toxicity. Only one patient remained on the standard dose of 2.5mg/kg for >3 cycles. Ocular toxicity improved after treatment interruption (drug intervals 4-6 weeks) and no patients required complete treatment cessation. One patient is too early to assess response. Haematological responses (PR or better) were seen in 7 patients with 3 complete responses and two very good partial responses (VGPR) which are ongoing. Both renal patients (patients 4 and 11) commenced a dose of 1.25mg/kg and sustained a VGPR with no additional toxicity. Patient 3 had a 42% reduction in sFLC after two doses but then a prolonged gap due to keratopathy and has lost the response. There were no cardiac or renal toxicities observed. Summary/Conclusion: Belantamab mafodotin demonstrates significant activity in patients with heavily pre-treated AL amyloidosis with 70% achieving a ≥PR. Apart from keratopathy requiring dose modification, no other substantial toxicity was observed. Two patients with renal impairment (stage V CKD and ESRD) and one patient post-renal transplant tolerated treatment with no additional toxicity. Belantamab mafodotin shows promise in treatment of relapsed AL and needs further prospective trials.
ABSTRACT
Introduction Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods Faecal and serum samples were prospectively collected from patients with IBD established on infliximab therapy (for >12 weeks) who were undergoing vaccination against SARS-CoV-2. The Roche Elecsys Anti-SARS-CoV-2 spike (S) and nucleocapsid (N) immunoassays were used to measure antibody responses following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Seroconversion was defined by a cut-off anti-S concentration of 15 U/ml, which correlated with 20% viral neutralization;anti-S antibody concentration of < 380 U/ml was indicative of poor response to vaccination. Patients with serological evidence of prior SARS-CoV-2 infection were excluded from the analysis. Faecal calprotectin measurement, 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-performance liquid chromatography mass spectrometry (UPLC-MS) were performed on faecal samples. Results Forty-five infliximab-treated patients were recruited (median age 40 [range 19-67];32 Crohn's disease, 13 ulcerative colitis;28 with concomitant immunomodulator therapy;six with prior infection). 14 patients (35%) had seroconverted after one dose of vaccine and 37 (95%) seroconverted after two doses. 18 patients (46%) had a poor response after two doses of vaccine. There was no association between faecal calprotectin and vaccine response (p=0.41). No differences between satisfactory and poor vaccine responders were noted in alpha or beta diversity of the gut microbiota. The faecal metabolome of satisfactory responders was enriched in the microbial metabolite trimethylamine (q=0.03). Trends were noted linking the short chain fatty acid butyrate with satisfactory response (P=0.01) and succinate with poor response (P=0.06). No significant differences in primary or secondary bile acids were found to associate with vaccine response. The butyrate-producing genus Roseburia was positively correlated with faecal butyrate abundance (q=0.03). Conclusions Our data suggest an association between gut microbiota function and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine and butyrate may be important in mitigating anti-TNF-induced attenuation of the immune response.
ABSTRACT
Introduction: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods: Faecal and serum samples were prospectively collected from patients with IBD established on infliximab therapy (for >12 weeks) who were undergoing vaccination against SARS-CoV-2. The Roche Elecsys Anti-SARS-CoV-2 spike (S) and nucleocapsid (N) immunoassays were used to measure antibody responses following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Seroconversion was defined by a cut-off anti-S concentration of 15 U/ml, which correlated with 20% viral neutralization;anti-S antibody concentration of < 380 U/ml was indicative of poor response to vaccination. Patients with serological evidence of prior SARS-CoV-2 infection were excluded from the analysis. Faecal calprotectin measurement, 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-performance liquid chromatography mass spectrometry (UPLC-MS) were performed on faecal samples. Results: Forty-five infliximab-treated patients were recruited (median age 40 [range 19-67];32 Crohn's disease, 13 ulcerative colitis;28 with concomitant immunomodulator therapy;six with prior infection). 14 patients (35%) had seroconverted after one dose of vaccine and 37 (95%) seroconverted after two doses. 18 patients (46%) had a poor response after two doses of vaccine. There was no association between faecal calprotectin and vaccine response (p=0.41). No differences between satisfactory and poor vaccine responders were noted in alpha or beta diversity of the gut microbiota. The faecal metabolome of satisfactory responders was enriched in the microbial metabolite trimethylamine (q=0.03). Trends were noted linking the short chain fatty acid butyrate with satisfactory response (P=0.01) and succinate with poor response (P=0.06). No significant differences in primary or secondary bile acids were found to associate with vaccine response. The butyrate-producing genus Roseburia was positively correlated with faecal butyrate abundance (q=0.03). Conclusion: Our data suggest an association between gut microbiota function and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine and butyrate may be important in mitigating anti-TNF-induced attenuation of the immune response.
ABSTRACT
Background : Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccineinduced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods: We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti- SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/ml, which correlated with 20% viral neutralization). Results: Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/ml;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/ml;p<0.0001) and uste (561U/ml;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/ml;p=0.62), nor between controls and vedo-treated patients (944U/ml;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69], p=0.002) and uste (0.56 [95% CI 0.31-1.00], p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11], p=0.17) or vedo (1.01 [95% CI 0.61-1.68], p=0.96). mRNA vaccines (3.67 [95% CI 2.72-4.96], p<0.0001) and older age (0.82 [95% CI 0.73-0.91], p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste. Conclusions : COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual's immunosuppressive treatment. (Figure Presented) (Figure Presented)
ABSTRACT
The aim was to evaluate patient satisfaction with virtual care, and identify factors associated with level of satisfaction. Surveys were mailed to all patients who had a phone visit at The Ottawa Hospital Rheumatology division. Patients' satisfaction with various aspects of the phone visits was assessed on a 5-point scale and analyzed according to demographic variables using chi-square and regression analyses. Of 2423 surveys mailed, we received 742 responses (31%). Eighty-nine percent of patients were satisfied overall with the phone visit. Statistically significant less satisfaction was seen in patients who spoke to a resident compared to their rheumatologist (p < 0.001), were not called on time (p < 0.001), had difficulty using a telephone (p < 0.001), needed assistance of a second person (p < 0.01), or had new consultations (versus routine follow-up, p = 0.01), the former 3 factors being significant in a multivariate regression analysis. Rheumatology patients expressed a high level of satisfaction with virtual care; however, areas of improvement were identified. Patients' satisfaction will be important to inform future decisions regarding the sustainability of virtual care. Further research is required to understand the impacts of virtual care on patients' Key Points ⢠Patients in rheumatology practice were satisfied with phone visits and preferred this method to in-person visits during the pandemic. ⢠Speaking directly to the rheumatologist, being phoned on time, and the capability of using the telephone were the major determinants of high patient satisfaction. ⢠Based on the identified factors, further improvement of the quality of and satisfaction with phone visits can be pursued given that virtual care may continue longer, beyond the pandemic.
Subject(s)
COVID-19 , Rheumatology , Telemedicine , Humans , Outpatients , Pandemics , Patient Satisfaction , TelephoneABSTRACT
Background: To investigate the outcome (30-day in-hospital mortality, length of stay and readmission within 28 days) of emergency inflammatory bowel disease (IBD) care in the Covid-19 pandemic. To quantify the reduction in provision of IBD investigations and procedures during the pandemic. Methods: Nationwide observational study using administrative data (Hospital Episode Statistics) for England (2015-2020). Autoregressive integrated moving average (ARIMA) forecast models were run to estimate the counterfactual IBD admissions and procedures for February 2020 onwards had the pandemic not occured. Results: Large decreases in attendances to hospital for emergency treatment were noted for both acute ulcerative colitis (UC) and Crohn's disease (CD) (17.4% and 10.3%). The prevalence of concomitant Sars-CoV- 2 infection during the same episode was low for UC and CD [1.7% (247/14,708) and 1.3% (179/14,126), respectively]. All IBD procedures and investigations showed marked decreases in volume to December 2020 compared to the counterfactual estimates. The largest absolute deficits were in lower gastrointestinal endoscopy (16,223, 35.7% reduction), reversal of ileostomy (2,489, 39.7% reduction) and right sided/ileal resection or strictureplasty for Crohn's disease (879, 12.5% reduction). There were no significant clinical differences in case mix or outcome of emergency admission for IBD in the pandemic compared to a historical cohort. Conclusion: There is likely a significant burden of untreated IBD in the community exacerbated by the pandemic based on reductions in emergency IBD care and IBD procedures undertaken in 2020. Patients with IBD may experience significant clinical harm or a protracted decrease in quality of life if care is not prioritised.
ABSTRACT
The year 2020 presented significant challenges to the field of kidney transplantation. After increasing each year since 2015 and reaching the highest annual count to date in 2019, the total number of kidney trans- plants decreased slightly, to 23642, in 2020. The decrease in total kidney transplants was due to a decrease in living donor transplants; the number of deceased donor transplants rose in 2020. The number of patients waiting for a kidney transplant in the United States declined slightly in 2020, driven by a slight drop in the number of new candidates added in 2020 and an increase in patients removed from the waiting list owing to death-important patterns that correlated with the COVID-19 pandemic. The complexities of the pandemic were accompanied by other ongoing challenges. Nationwide, only about a quarter of waitlisted patients receive a deceased donor kidney transplant within 5 years, a proportion that varies dramatically by donation service area, from 14.8% to 73.0%. The nonutilization (discard) rate of recovered organs rose to its highest value, at 21.3%, despite a dramatic decline in the discard of organs from hepatitis C-positive donors. Nonutilization rates remain particularly high for Kidney Donor Profile Index ≥85% kidneys and kidneys from which a biopsy specimen was obtained. Due to pandemic-related disruption of living donation in spring 2020, the number of living donor transplants in 2020 declined below annual counts over the last decade. In this context, only a small proportion of the waiting list receives living donor transplants each year, and racial disparities in living donor transplant access persist. As both graft and patient survival continue to improve incrementally, the total number of living kidney transplant recipients with a functioning graft exceeded 250,000 in 2020. Pediatric transplant numbers seem to have been impacted by the COVID-19 pandemic. The total number of pediatric kidney transplants performed decreased to 715 in 2020, from a peak of 872 in 2009. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients, with continued racial disparities among recipients. Of concern, the rate of deceased donor transplant among pediatric waitlisted candidates continued to decrease, reaching its lowest point in 2020. While this may be partly explained by the COVID-19 pandemic, close attention to this trend is critically important. Congenital anomalies of the kidney and urinary tract remain the leading cause of kidney disease in the pediatric population. While most pediatric de- ceased donor recipients receive a kidney from a donor with KDPI less than 35%, most pediatric deceased donor recipients had four or more HLA mis- matches. Graft survival continues to improve, with superior survival for living donor recipients versus deceased donor recipients.
Subject(s)
COVID-19 , Tissue and Organ Procurement , COVID-19/epidemiology , Child , Graft Survival , Humans , Kidney , Living Donors , Pandemics , Registries , SARS-CoV-2 , Tissue Donors , United States/epidemiology , Waiting ListsABSTRACT
Background: Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody. Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination. Methods: Anti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine. Results: Anti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/ mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1). Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 - 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2). There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumabtreated patients after one or two doses of either vaccine. Antibody half-life was shorter in infliximab- than vedolizumabtreated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 - 4.1] vs 7.2 weeks [95% CI 6.8 - 7.6]) and ChAdOx1 nCoV- 19 (5.3 weeks [95% CI 5.1 - 5.5] vs 9.3 weeks [95% CI 8.5 - 10.2], p value < 0.0001). Breakthrough SARS-CoV-2 infections were more frequent (5.8% (202/3467) vs 3.9% (66/1691), p = 0.0032) and the time to breakthrough shorter in patients treated with infliximab than vedolizumab (p = 0.0023) (Fig. 3). Higher anti-S RBD antibody concentrations following a second dose of SARS-CoV-2 vaccine protected against breakthrough SARS-CoV-2 infection: overall, for every 10-fold rise in anti-S RBD antibody level we observed a 0.8-fold reduction in odds of breakthrough infection ([95% CI 0.70 - 0.99], p = 0.035). Conclusion: Infliximab was associated with attenuated, less durable vaccine induced anti-S RBD antibody responses and a 50% increase in breakthrough SARS-CoV-2 infection. Further follow-up is required to assess whether third primary doses can mitigate the effects of infliximab on anti-S RBD antibody responses.
ABSTRACT
Background: Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods: We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti- SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/mL, which correlated with 20% viral neutralization). Results: Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/mL;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/mL;p<0.0001) and uste (561U/mL;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy- treated patients (1020U/mL;p=0.62), nor between controls and vedo-treated patients (944 U/mL;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69], p=0.002) and uste (0.56 [95% CI 0.31-1.00], p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11], p=0.17) or vedo (1.01 [95% CI 0.61-1.68], p=0.96). mRNA vaccines (3.67 [95% CI 2.72- 4.96], p<0.0001) and older age (0.82 [95% CI 0.73-0.91], p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste. Conclusion: COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual's immunosuppressive treatment.
ABSTRACT
Background : Management of ITP became increasingly challenging during the COVID-19 pandemic. Immunosuppressive treatments increase susceptibility of patients to COVID-19. Therapies increasing the thrombotic risk are suboptimal due to coagulopathy observed with COVID-19. The need to minimize office visits to limit potential viral exposure renders intravenous administration or injections less suitable. Consequently, ITP management requires careful patientcentric consideration during the pandemic. Fostamatinib is a potent oral SYK inhibitor that abrogates SYKmediated destruction of platelets and may abrogate SYK-mediated thromboinflammation. Aims : To evaluate fostamatinib as an ITP treatment during the COVID-19 era. Methods : Review of safety, immunotoxicology, and mechanism of action and administration for fostamatinib. Results : Preclinical studies demonstrated intact innate and humoral responses to immune challenges in fostamatinib (R406) treated rodents. 1 In ITP clinical trials, the incidence of adverse events (including infections) was somewhat higher with fostamatinib vs placebo (83% vs 75%), which is consistent with the 2.4-fold increase in exposure to fostamatinib vs. placebo (29 vs. 12 patient-exposure years, respectively). No patients had opportunistic infections. The rate of thromboembolic events with fostamatinib (0.7% over 5 years) was low compared with similar studies with other ITP treatments (2.6-8.9% over 2-8 years). Office visits can be minimized due to oral administration of fostamatinib and simplified titration: fostamatinib is initiated at 100mg BID and increased to 150mg BID after 4 weeks if needed. Thrombocytosis was uncommon (1.4% over 5 years). Conclusions : Fostamatinib is an immunomodulatory treatment for ITP that may lower the risk of thrombosis. The need for office visits may be reduced due to oral administration, simplified titration, and infrequency of thrombocytosis. Fostamatinib is an appropriate option for the treatment of ITP in the COVID-19 era.
ABSTRACT
Manufacturing processes is a key subject in undergraduate engineering curricula, and ideally blends theory with hands-on activities and exposure to manufacturing practice. Therewith, the emergence of scalable, versatile digital learning tools and techniques suggests that manufacturing courses should explore how to maximize the use and value of in-person teaching time. This paper describes the application of a flipped classroom model to undergraduate manufacturing processes courses at the Massachusetts Institute of Technology and the University of Michigan. In the flipped classroom approach, pre-recorded lecture videos are provided to students, and in-class time is used for hands-on activities and/or labs, thereby promoting discussion and interaction among students and staff. Together, the combination of online preparation and in-person learning is designed to: (1) study manufactured products, and relate observations to fundamental principles;(2) encourage formulation of questions based on open-ended topics;(3) practice written, verbal, and graphical communication skills;and (4) build a layered understanding of manufacturing as a complex system that connects process physics to overarching principles of rate, quality, cost, and flexibility. We also share our experiences teaching during the COVID-19 pandemic, which necessitated a balance of remote and in-person learning, and comment on emerging curriculum elements including use of augmented reality. © 2021 The Authors. Published by Elsevier B.V.
ABSTRACT
Purpose: COVID-19 causes more severe complications in older patients and disproportionately leads to poor outcomes in racial minorities. High offer acceptance rates indicate better access to transplant. Because access to transplant is critical for patients with end-stage organ failure, we investigated the effect of COVID-19 on offer acceptance rates by candidate age and race before and after the national emergency declaration on March 13, 2020 for kidney, liver, lung, and heart transplant. Methods: We used match run data from March 13, 2019 to August 31, 2020 and included offers that resulted in at least 1 acceptance. Logistic regressions estimated differences in offer acceptance by candidate age and race before and after COVID-19 (i.e., the effects for age and race interacted with an indicator of donors recovered after March 12, 2020), and the regressions adjusted for the location of the offer in the match run and other candidate and donor characteristics. Results: Overall, offer acceptance rates were lower for kidney, liver, and heart transplant after COVID-19 than before (Table 1). Differences in kidney offer acceptance across candidate age had a dose-response relationship: offer acceptance rates were higher in younger kidney candidates before and after COVID-19 than in older candidates. Offer acceptance rates for Black and Asian candidates decreased more before and after COVID-19 than for White candidates (Table 1). Offer acceptance rates for liver, lung, and heart candidates did not notably differ before and after COVID-19 by candidate age and race. Conclusions: Thus, COVID-19 inequitably affected kidney offer acceptance rates across candidate age and racial groups.
ABSTRACT
Background: Management of immune thrombocytopenia (ITP) has become increasingly challenging during the COVID-19 pandemic. Immunosuppressive treatments used to treat ITP can increase the susceptibility of patients to develop COVID-19. Additionally, therapies which increase the risk of thrombosis may not be optimal due to the hypercoagulable state also observed in patients with COVID-19 infection. The need to minimize office visits, to limit potential exposure to the virus, renders therapies requiring intravenous administration or injections as well as treatments requiring frequent titration less suitable. Consequently, ITP management requires careful patient-centric consideration during the pandemic. Aims: To evaluate fostamatinib as an ITP treatment during the COVID- 19 era Methods: Review of the safety data from the phase 3 studies for fostamatinib in ITP as well as titration and mode of administration. Results: Patients (n=146) in the trials had a median age of 53 years (range 20-88), a median of 5 prior ITP treatments, and 229 years of fostamatinib exposure. An increase in platelet count ≥50,000/μL was observed in 54% of patients on fostamatinib treatment. These patients maintained their response to treatment for 86% of treatment days. In the placebo-controlled phase, there was a 2.4-fold difference in duration of exposure to fostamatinib vs. placebo (29 vs. 12 patient-exposure years, respectively). Consequently, the incidence of infections with fostamatinib was somewhat higher than with placebo (27% vs. 21%). The incidence of overall adverse events was similarly higher with fostamatinib vs placebo (83% vs 75%). No patients had opportunistic infections. Office visits can be minimized due to oral administration of fostamatinib and simplified titration. Fostamatinib dosing is initiated at 100mg BID in patients and increased to 150mg BID after 4 weeks if needed. Titration visits are also minimized due to the low incidence of thrombocytosis (1.4% over 5 years). ITP patients have an increased risk of thrombotic events, which may be due to SYK-dependent platelet activation in patients with ITP.2 In the randomized fostamatinib studies, 87% of patients had at least one risk factor for thrombosis, and 58% had multiple risk factors. Over the 62-month study, one (0.7%) thrombotic event was reported: a patient with pre-existing atherosclerosis had a mild transient ischemic attack, which resolved spontaneously. This rate is lower than seen in long-term ITP clinical trials (2-8 years duration), which ranged from 2.6% to 8.9%. Summary/Conclusion: Fostamatinib is an immunomodulatory treatment that elevates platelet counts and may lower the risk of thrombosis in ITP. There is also a reduced need for office visits due to oral administration, simplified titration, and infrequency of thrombocytosis. Fostamatinib is an appropriate therapeutic option for the treatment of ITP in the COVID-19 era.