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Background: Filter paper (FP) or dried blood spot testing is the preferred method of monitoring blood levels of phenylalanine and tyrosine for patients diagnosed with phenylketonuria (PKU) in the state of Georgia. This cost effective and convenient at-home approach simplifies the nutritional assessment and management of patients with PKU and lessens the burden on patients and caretakers. Emory and a local specialty laboratory had a long-standing contract for FP testing, which included patient insurance and grant billing. When this laboratory abruptly ended FP testing in September 2020, an emergent alternative plan became essential to prevent potential disruptions in patient care while working on a sustainable solution for PKU monitoring, especially given the ongoing COVID-19 pandemic. Method(s): Emory's in-house laboratory was not contracted with outside laboratories to process FP testing and bill insurance. To mitigate any delays in FP testing, the MNT4P program conducted a vendor search and selected ARUP Laboratories to perform PKU FP testing. Eligible patients included those referred, enrolled, and consented to the MNT4P program. To streamline the FP submission process, customized FP cards and business reply envelopes were developed and distributed in collaboration with PerkinElmer, Emory Mail Services and the United States Postal Service. Patient outreach efforts were facilitated through email campaigns, MNT4P website updates, and in collaboration with Georgia PKU Connect. Result(s): 95 patients were referred to MNT4P program for FP paper monitoring. During the 4-month period, a total of 239 FPs were collected from patients with PKU and processed with corresponding results reported to Emory Clinic, allowing registered dietitians to continue nutrition management without disruption. Once the patient-centered business prototype was established, FP testing was successfully transferred from the MNT4P program to Emory's inhouse laboratory. FP testing is now a part of Emory's test catalog, and results are available to providers through electronic health records. Conclusion(s): The MNT4P program successfully worked with Emory's in-house laboratory to develop a sustainable solution for FP monitoring. It prevented interruption in long-term follow up of patients with PKU. MNT4P continues to be the payor of FP tests for uninsured and underinsured patients.Copyright © 2022 Elsevier Inc. All rights reserved.
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INTRODUCTION: Redeployment of orthopaedic consultants to a minor injuries unit (MIU) during the COVID-19 pandemic provided a unique opportunity to assess the impact of early senior specialist input on patient management. METHODS: Patient demographics, diagnosis, location of injury and disposal method were compared between three 7-day periods: during the April 2020 COVID-19 lockdown (period A), one month prior to period A (period B) and one year prior to period A (period C). Orthopaedic consultants staffed the MIU during period A, and emergency nurse practitioners staffed the MIU during periods B and C. RESULTS: Period A witnessed higher injury severity either due to modified activities or altered healthcare-seeking behaviour during lockdown. For fractures, compared with periods B and C, period A saw a lower rate of referral to fracture clinic (41% vs 100% vs 86%, p<0.001) and higher rate of discharge (38% vs 0% vs 9%, p<0.001). The median time to fracture clinic was also longer (15 days vs 6 days vs 10 days, p<0.001), indicating earlier institution of definitive care. There were no other significant differences between periods with radiology alerts and complaints received remaining largely unchanged. CONCLUSION: Early senior orthopaedic input in the patient journey from MIU had clear benefits, this being most true for fracture diagnoses. Earlier definitive management planning was observed as lower rates of fracture clinic referral, higher rates of discharge and deferred first fracture clinic reviews. This study highlights the benefits of greater partnership between MIU and orthopaedics. As the pandemic subsides and redeployed staff return to normal duties, a modification of this model could be utilised to ensure this partnership is sustainable.
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Background. There remain important gaps in knowledge concerning the effects of SARS-CoV-2 infection or vaccination on the human blood proteome. Methods. The CCRP is a longitudinal surveillance study with information on SARS-CoV-2 infections, vaccinations and associated humoral immune responses in over 37,000 individuals. We selected a sample of blood spots cards (n=510) from serum antibody studies obtained between October 2020 and April 2021 for mass spectrometry proteomics analysis covering 540 unique plasma proteins. We analyzed the quantified protein differences based on dried blood samples obtained before and after infection or vaccination among previously non-infected individuals (immune naive) after adjustment for batch effects, age, sex, or prior diagnosis of cancer, cardiovascular or autoimmune disease, or diabetes. The majority of infected individuals were minimally symptomatic. Differentially expressed proteins were considered significant with an FDR adjusted p-value of < 0.05 and log2 fold change (L2FC) >0.2. Results. We found 11 and 12 proteins differentially expressed proteins in the naive/infected and naive/vaccinated people respectively, of which 10 were shared. Hepatocyte growth factor receptor (HGF) was upregulated (L2FC 0.24;p < 0.001) only in those who were infected while fibrillarin (L2FC -0.24;p< 0.001) and lambdacrystallin homolog (L2FC -0.29, p < 0.001) were downregulated only in the vaccinated samples (Fig 1). The remaining DE protein were associated with a wide array of functions including metabolic, cytostructural, extracellular matrix and DNA regulatory processes. Conclusion. We found changes in the proteome both from infection and vaccination. HGF, elevated in the infected, has been associated with endothelial inflammation, upregulation of pro-inflammatory cytokines to reduce lung fibrosis and is known to promote tissue repair. Fibrillarin, downregulated in the vaccinated, has been associated with higher rates of bacterial and viral clearance, inflammation reduction, and increased cell survival. These findings suggest detectable complex inflammation from mild to moderate infections. Further investigation is required to understand the mechanism of action and clinical implication of these findings.
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Background. The COVID-19 Community Research Partnership (CCRP) is a large multicenter healthcare system-based study of the COVID-19 pandemic, including factors impacting risk of infection and hospitalization. The CCRP includes a subset of immunocompromised (IC) participants with varying vaccination status over time. Methods. We conducted an observational cohort study of 2,515 IC and 41,941 non-IC CCRP participants who contributed electronic health record data and daily electronic surveys to self-report COVID-19 symptoms, test results, and vaccinations from April 2020 to March 2022. The IC population included those with stem cell transplant, HIV, cancer, autoimmune disease, or solid organ transplant. The latter 3 must have also had an active systemic therapy to meet the IC condition (e.g. chemotherapy, immune modulator, steroid). Logistic regression was used to investigate risk of COVID-19 and hospitalization among IC participants and according to vaccine status within viral variant time periods (pre-delta, delta, omicron). Results. IC conditions included cancer (51%), autoimmune (41%), solid organ/ stem cell transplant (9%), and HIV (7%). The IC group was older and had more comorbidities. 95% of vaccine recipients received an mRNA vaccine. More vaccine breakthrough infections occurred in the IC group than non-IC group (36.1% vs 29.5%, p< 0.001). IC participants were less likely to remain COVID-19 free over time if vaccinated but not boosted (Fig 1A). However, after receiving a booster there was no difference in COVID-19 cases between the groups (Fig 1B). IC participants were more likely to be hospitalized with COVID-19 (OR 2.85;95% CI 1.69-4.76), but vaccination reduced risk for hospitalization (OR 0.26;95% CI 0.08-0.8). Receipt of a booster dose reduced risk of COVID-19 among IC participants during the delta wave (IRR 0.52;95% CI 0.28-0.94) but not during omicron. However, during omicron risk of hospitalization in the IC group was reduced by a booster dose (OR 0.13;95% CI 0.02-0.72). Conclusion. IC individuals were at increased risk for COVID-19 hospitalizations and breakthrough infections. After receiving a booster, IC participants were conferred the same level of protection from infection as their non-IC counterparts, highlighting the importance of boosters for these individuals. (Figure Presented).
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As the COVID-19 pandemic has demonstrated, barriers to vaccination uptake are heterogeneous and vary according to the local context. We argue that a more systematic consideration of local social and behavioural mechanisms could improve the development, assessment and refinement of vaccination uptake interventions. The EBM+ approach to evidence appraisal, which is a development of a recent line of work on the epistemology of causality, provides a means to evaluate mechanistic studies and their role in assessing the effectiveness of an intervention. We argue that an EBM+ methodology offers several potential benefits for research on vaccination uptake interventions. It also motivates the use of detailed mechanistic models, rather than the high-level logic models used by process evaluations, for example. © 2021 University of Sassari
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Background. Studies have shown the proportion of critically ill patients with COVID-19 receiving empiric antibiotics (ABX) greatly exceeds those with culture-proven bacterial co-infections. However, the benefits of continuing ABX in culture-negative (CxN) cases is unknown;this practice may increase the risks associated with ABX overuse. The purpose of this study was to evaluate outcomes and antibiotic use (AU) in intensive care unit (ICU) patients with COVID-19 based on culture results. Methods. This was a multicenter, retrospective cohort study evaluating adults in an ICU for the first episode of ABX initiated following a confirmed COVID-19 diagnosis between September to December 2020. Blood and/or respiratory cultures must have been obtained within 24 hours (h) of ABX initiation. Patients were categorized into three groups: 1) CxN, ABX discontinued ≤ 72 h, 2) CxN, ABX continued > 72 h, or 3) Culturepositive (CxP). Data on AU was obtained from electronic medication administration records. The primary outcome was clinical success, defined as being discharged alive or > 2-point decrease in the World Health Organization Clinical Progression Scale score from day of ABX initiation to day 30. Results. A total of 65 patients were included with 35.4% being CxP. ABX were discontinued ≤ 72 h in 23.8% of CxN patients. Methicillin-susceptible Staphylococcus aureus was the most common organism in 52.2% of CxP patients (66.7% respiratory;16.7% blood;16.7% both). Anti-methicillin-resistant Staphylococcus aureus and anti-pseudomonal antibiotics were the most prescribed for the initial regimen (Table 1). ABX de-escalation occurred in 58.5% of patients. Initial ABX duration was significantly longer in the CxP group (P < 0.01). No significant difference in clinical success was observed (Table 2). Although not significantly different, the highest rate of adverse events occurred in the CxN and ABX continued > 72 h group (40.6%). Conclusion. In ICU patients with COVID-19, empiric broad-spectrum ABX are often overutilized with an inertia to de-escalate despite negative culture results, potentially increasing the risk of adverse events. This remains an important area for focused antimicrobial stewardship efforts to mitigate the development of multidrug resistance.
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OzNomads are lifestyle travellers who practice extreme mobilities and are independent of specific geographic locations. The COVID-19 pandemic, and subsequent measures imposed by federal and state governments to control it, have had adverse effects on the OzNomad community. In stark contrast to the benefits of the lifestyle prior to the pandemic, this paper outlines five emerging challenges facing OzNomads: displacement, marginalization, social isolation, financial impacts and mental health. Such challenges have serious implications for the wellbeing of a community that contributes substantially to regional and rural Australia as workers, consumers and volunteers.
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Aim: The ongoing Covid-19 pandemic has interrupted surgical treatment of colorectal cancer (CRC). This systematic review will assess literature concerning the risk of delay of elective surgery for CRC patients, focusing on overall survival (OS) and disease-free survival (DFS). Methods: A systematic review was performed as per PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were searched. Patients over 18 with a diagnosis of colon or rectal cancer who received elective surgery as primary treatment were included. Delay was defined as the period between CRC diagnosis and day of surgery. Metanalyses of the outcomes OS and DFS were conducted. Forest plots, funnel plots, tests of heterogeneity, and estimated Number Needed to Harm (NNHs) were produced. Results: Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314560 patients, three of the seven studies showed a delay to elective resection was associated with poorer OS or DFS. OS was assessed at a one-month delay, the HR for six datasets was 1.13 (95%CI 1.02-1.26, p=0.020) and at three months the HR for three datasets was 1.57 (95%CI 1.16-2.12, p=0.004). Estimated NNHs for a delay at one month and three months were 35 and 10 respectively. Delay was nonsignificantly negatively associated with DFS on metanalysis. Conclusions: This review recommends elective surgery for CRC patients is not postponed longer than four weeks, as evidence suggests extended delays from diagnosis are associated with poorer outcomes. Focused research is essential so patient groups can be prioritized based on risk-factors for future pandemics.
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Background: The ongoing Covid-19 pandemic has interrupted the surgical treatment of colorectal cancer (CRC). This systematic review will assess literature concerning the risk of delay of elective surgery for CRC patients, focusing on overall survival (OS) and disease-free survival (DFS). Methods: A systematic review was performed as per PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were searched. Delay to elective surgery was defined as the period between CRC diagnosis and the day of surgery. Metanalyses of the outcomes OS and DFS were conducted. Forest plots, funnel plots, and tests of heterogeneity were produced. An estimated Number Needed to Harm (NNH) was calculated for statistically significant pooled Hazard Ratios (HRs). Results: Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314560 patients, three of the seven studies showed that a delay to elective resection is associated with poorer OS or DFS. OS was assessed at a one-month delay, the HR for six datasets was 1.13 (95% CI: 1.02-1.26, P = 0.020) and at three months the pooled HR for three datasets was 1.57 (95% CI: 1.16-2.12, P = 0.004). Estimated NNHs for a delay at one month and three months were 35 and 10 respectively. Delay was non-significantly negatively associated with DFS on meta-analysis. Conclusions: This review recommends that elective surgery for CRC patients is not postponed, as evidence suggests delays from diagnosis are associated with poorer outcomes. Focused research is essential so that patient groups can be prioritized based on risk factors for future pandemics.