Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial.

PURPOSE: Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness. METHODS: Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation. RESULTS: We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019). CONCLUSION: These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.

P2/N95 fit testing and the risk of COVID-19 in Healthcare Workers.

BACKGROUND: Guidelines recommend healthcare workers (HCWs) undertake fit testing of P2/N95 respirators to mitigate the risk of infectious aerosols, however few studies have assessed whether fit testing reduces COVID-19 infection. METHODS: A retrospective cohort study was conducted amongst HCWs across two tertiary health services in Melbourne, Australia during a period of low community transmission. Institution-wide quantitative fit testing and detailed questionnaires assessing COVID-19 acquisition risk factors were undertaken from September 2020. HCWs diagnosed with COVID-19 in the period prior to the fit testing program (February 1st - August 31st 2020) were matched on a 1:3 ratio to HCWs who had not been diagnosed with COVID-19. Risk factors for COVID-19 acquisition, including fit testing outcome, were compared between groups. RESULTS: A total of 1571 HCWs took part in fit testing programs. Seventy-two (4.6%) were diagnosed with COVID-19 within the study period. Younger age, nursing staff, close contact with a COVID-19 case, and working longer periods in wards with COVID-19 patients, were associated with COVID-19 infection. After matching for intensity of occupational exposure to infectious aerosols, close contact was the only independent variable associated with COVID-19 infection (OR 3.50, 95% CI:1.65-7.44, p = 0.001). Adequate fit test for the respirator predominately worn before the fit testing period was not associated with COVID-19 (OR 1.08, 95% CI:0.59-1.98, p = 0.815). CONCLUSION: After controlling for intensity of occupational exposure to infectious aerosols, P2/N95 respirator fit testing was not associated with reduced risk of COVID-19 infection. The utility of widespread fit testing to reduce HCW COVID-19 infections should be reconsidered.

Quality of life outcomes in children with Hirschsprung disease.

BACKGROUND: Morbidity following repair of Hirschsprung disease (HD) is common. However, quality of life (QoL) results focused on HD children are contradictory. We aimed to measure QoL outcomes in HD children using validated questionnaires. METHODS: Patients with HD, managed at a large tertiary pediatric institution between 2004 and 2013, were identified. Parents completed validated questionnaires. Results were compared with published healthy population controls. QoL outcomes were measured using Pediatric Quality of Life (PedsQL) and Fecal Incontinence and Constipation Quality of Life (FIC QOL). Functional outcomes were assessed using Baylor Continence Scale, Cleveland Clinic Constipation Scoring System, and Vancouver Dysfunctional Elimination Syndrome Survey. RESULTS: Parents of 60 HD patients [M:F 49:11; median age 6.4years (2.3-10.9)] were interviewed (59% participation). The majority (47/60, 78%) had rectosigmoid disease. There was significant reduction in psychosocial (social and emotional) QoL compared with healthy children (p=0.03). Psychosocial functioning was affected by increasing age (r=-2.72, p<0.001), fecal incontinence (r=-0.475, p=0.007), constipation (r=-1.58, p=0.006), and dysfunctional elimination (r=-2.94, p=0.004). Fecal incontinence also reduced physical functioning QoL (r=-0.306, p=0.007). Children with HD had significantly higher levels of fecal incontinence (p<0.01). CONCLUSIONS: We have demonstrated that HD children have significant reductions in psychosocial QoL and functional outcomes. LEVEL OF EVIDENCE: Prognosis Study - Level II (Prospective cohort study).