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Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
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INTRODUCTION: There is wide variation in the management of simple subcutaneous abscesses in the UK and no national guidelines describing best practice. During the SARS-CoV-2 pandemic, regional or local anaesthesia (LA) use was recommended instead of general anaesthesia. This study aimed to assess the effect of anaesthetic use on outcomes following incision and drainage (I&D) of simple subcutaneous abscesses. METHODS: Two cohorts of patients undergoing abscess incision and drainage at St. James' University Hospital in Leeds were identified retrospectively over a 14-week period before (P1) and after (P2) the introduction of the COVID-19 anaesthetic guidelines. The number of follow-up appointments for repacking and representation to healthcare services 30 days after I&D were used as surrogate endpoints for wound healing. RESULTS: A total of 133 patients were included (n=70, P1 and n=63, P2). Significantly more procedures were performed under LA after the intervention (84.1% vs 5.7%; p<0.0001) with a significant reduction in wound packing (68.3% vs 87.1%; p=0.00473). Follow-up analysis found no significant difference in the median number of follow-up appointments (7.46 vs 5.11; p=0.0731) and the number of patients who required ongoing treatment after 30 days (n=14, P1 vs n=14, P2; p=0.921). CONCLUSIONS: Drainage of simple subcutaneous abscess under 5cm in diameter is safe under LA, with no significant difference in surrogate endpoints of wound healing observed in this patient cohort. Recurrent packing may not be required. Future work should explore patient-reported outcomes, including pain management, cosmesis and the cost and sustainability implications of a change in this common procedure.
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Aims: Despite being the most common surgical procedure, there is wide variation that exists in the management of simple subcutaneous abscesses with no national guideline describing best practice. During the COVID-19 Pandemic national guidelines promoted the use of regional or local anaesthetic (LA) instead of general anaesthesia (GA) to avoid aerosol generating intubation associated with GA. This study aimed to assess the impact of anaesthetic choice in outcomes following incision and drainage of subcutaneous abscesses. Methods: Two cohorts of patients undergoing abscess incision and drainage at St. James' University Hospital Leeds were retrospectively identified over a 14-week period before and after the introduction of the new COVID-19 anaesthetic guidelines. Wound healing surrogate endpoints were used: i) total number of follow up appointments and ii) attendance to healthcare services after 30 days from I&D. Result: 133 patients were included. Significantly more procedures were performed under LA after the intervention (84.1% vs 5.7%;p<0.0001) with a significant reduction in wound packing (68.3% vs 87.1%. p=0.00473). Follow up data found no significant difference in the average number of follow-up appointments (7.46 vs 5.11;p=0.0731) and the number of patients who required ongoing treatment after 30 days (n=14 vs n=14, p=0.921). Conclusion: Drainage of simple subcutaneous abscess under 5cm is safe under local anaesthetic with no significant difference in surrogate endpoints of wound healing observed in this patient cohort. Recurrent packing may not be required. Future work should explore patient reported measures such as pain management and the health economics of this intervention.
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Issue: Co-enrollment of patients in trials of complex interventions is an emerging phenomenon. Co-enrollment can provide efficiencies, pertinent in the era of a pandemic, but is not without issue. Management of patient co-enrollment, especially in trials investigating multiple interacting components, such as surgical randomized controlled trials, is considered. Setting: IntAct is an international surgical trial which has recruited throughout the COVID pandemic. It is a prospective, parallel group, randomized controlled trial comparing surgery with intraoperative fluorescence angiography against standard care (surgery alone) to determine the effect on anastomotic leak in patients undergoing resection for rectal cancer. Co-enrollment of patients has been requested by nine other trials to date, ranging from interventional drug trials to observational studies. There is minimal published literature regarding co-enrollment to inform discussion and decision-making by the IntAct Trial Management group. Background: Co-enrollment of patients in clinical trials poses a number of potential issues spanning ethical, safety, statistical, and practical concepts, which require careful consideration. Effort has been made to quantify the potential impacts of co-enrollment on statistical power (Myles, 2014). For example, the interaction of treatment effects and substantial or imbalanced co-enrollment have been shown to possess the potential for a large detrimental effect on the sample size. In practice, the nature of such an interaction, or the level of co-enrollment, will not be known in advance. Furthermore, where the intervention is complex in nature, such as in surgical trials of multiple component parts like IntAct, not only is there the possibility of an interaction between the treatment effects of co-enrolling interventions, but also of how the co-enrolling intervention may alter the individual intervention components. There is no published guidance on how to assess these risks a priori. Nonetheless, there are also many potential benefits to allowing co-enrollment. These include increased availability of research opportunities to patients and increased efficiencies to sites when patients contribute to multiple research projects. Disallowing co-enrollment could pose a risk to a trial's recruitment by narrowing the pool of potential participants. Likewise, there is no published guidance on how to assess these benefits a priori. Key considerations for co-enrolling trials: the IntAct Trial Management group decision-making process was informed by discussions regarding: • Internal validity: the ability of the co-enrolling intervention to change the typical operative setting, as well as the post-operative care pathway. • Potential interaction of treatment effects: particularly with regard to the primary endpoint and participant safety. • Generalizability: the possible implications for the trial results. • Recruitment impact: the probable restrictions imposed if co-enrollment was disallowed. • Compliance: the likely effects of co-enrollment on data collection, follow-up visits and withdrawal, and ethical considerations of overburdening participants. We present our rationale and recommendations for guiding Trial Management group discussions when considering and approving co-enrollment of patients in clinical trials. By presenting the experiences of the IntAct international surgical trial Trial Management group, we provide a practical reference for trials considering co-enrollment.
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Introduction: In the United Kingdom, there are no widely used guidelines within the management of subcutaneous abscesses by incision and drainage (I&D) to direct the use of local anaesthesia (LA) vs genal anaesthesia (GA);or the use of wound packing vs no packing. Method: Two cohorts of patients undergoing I&D procedures were retrospectively identified from attendance records over a 3.5-month period. The first cohort was between 16th October 2018 to 31st January 2019. The second cohort of patients was during the COVID-19 pandemic following the introduction of new RCS guidance (intervention) between 29th March 2020 and 15th June 2020. Results: Seventy-one patients before and 63 after the intervention were included. There were significantly more procedures performed under LA after the introduction of the intervention (n=52;82.5%) vs before (n=4;5.6%) p<0.0001. The incidence of wound packing decreased after the intervention (n=43;68.3% vs n=62;87.3%) p=0.00452. Conclusions: The results demonstrate that during the pandemic, change in practice resulted in more subcutaneous abscesses being treated with LA. The majority of abscesses were packed in both cohorts although the incidence declined after the intervention. Future research should explore the patient satisfaction regarding pain management and the abscess recurrence rate.
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What are the new findings? ►► The COVID-19 pandemic prevented physical innovation formats and virtual innovation strategies such as the virtual hackathon proposed in this article may address this challenge. ►► Virtual interdisciplinary collaboration between students and early career professionals can ead to rapid innovations to address urgent unmet clinical needs in times of global emergencies. How might it impact on healthcare in the future? ►► Innovation pathways should be augmented with virtual innovation strategies to break down barriers to engagement in healthcare innovation, improve global interdisciplinary collaboration and enhance rapid innovation adoption moving into the future. ►► Particular healthcare technologies likely to be positively impacted by this include those in digital health, global health and medical device sectors. © 2021 Georg Thieme Verlag. All rights reserved.