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Background: The spread of COVID-19 was inevitable and has not spared small and isolated communities, including the community on Perhentian Island in Besut District, Terengganu. Managing clusters in small islands can be difficult, given the limited resources. This study explores the characteristics of COVID-19 cases and the experience of outbreak containment at Perhentian Island. Methodology: A retrospective study involving record review of COVID-19 cases and at-risk individuals registered under the Perhentian Cluster were retrieved from the Besut District Health Office COVID-19 online registry from the 16th August 2021 until 6th October 2021. All notified cases and close contacts who fulfilled the inclusion criteria were extracted and analysed using descriptive statistics. Result(s): A total of 1,093 out of 2,500 community members of Perhentian Island were screened of which 170 (15.5%) tested positive for COVID-19, while 923 (84.5%) tested negative. Among individuals who tested positive, the majority were adults (52.4%), males (51.8%), Malays (98.8%), and villagers (96.5%). Clinical characteristics were categorized into: asymptomatic (55.9%), had no known medical comorbidities (90.6%), low-risk groups (87.1%), vaccinated (57.6%), and admitted to PKRC (97.1%) for treatment. Multiple agencies were involved in the outbreak containment of the Perhentian Cluster, working collectively and in good coordination. Conclusion(s): The outbreak was attributed to community gatherings and close interactions among villagers. Prompt actions, targeted planning, and inter-agency collaboration were the key factors in successful containment of further spread of COVID-19 in Perhentian Island.Copyright © 2023, Faculty of Medicine, University of Malaya. All rights reserved.
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Background: A considerable number of front-line workers are under risk due to repeated infection and exposure. The pattern of COVID 19 infection among the front-line workers was important, so that more focus would be laid on protecting them. Contact tracing is one key strategy for interrupting chains of transmission of SARS-CoV-2. This study aimed to find the pattern of COVID 19 infection among front line health workers and describe the process of contact tracing. Methodology: The list of front-line workers with possible symptoms of COVID-19 or had come in direct contact with a "case" was shared with the department of community medicine for contract tracing activity as per the guidelines. The front-line workers who were categorized as High Risk were quarantined immediately and those who were categorized as Low-Risk were advised to be vigilant regarding the development of symptoms and were asked to continue with their routine duties with extra precautionary measures as they form a very vital part of the resource in this combat against COVID-19. Result(s): About 138 front line health workers were affected by COVID-19 among which staff nurses (51) amounted to the maximum number who were affected. Conclusion(s): COVID-19 was high among front-line workers and had a large number of high-risk contacts. Nurses were found to be most affected with COVID 19 infection.Copyright © 2023, Institute of Medico-legal Publication. All rights reserved.
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Role of asthma as a risk factor in severity and mortality in COVID-19 varies in literature. In 2020, 4CMortality score was published, which through 8 parameters in the initial evaluation (age, sex, comorbidity index Charlson, respiratory rate, peripheral oxygen saturation, renal function, Glasgow scale and C-reactive protein) stratified risk of in-hospital mortality from COVID-19 into low(0-3 points), intermediate(4-8), high(9-14) and very high(from 15). Our objective is to assess usefulness of 4CMortality in asthmatic patients admitted for COVID-19 and to verify the degree of correlation between the score and the mortality data and hospital stay. Observational retrospective study of asthmatic patients admitted for COVID-19 between March 2020 and March 2021. Statistical analysis is performed using Fisher's exact test(risk scale-death), ANOVA(risk scale-days hospitalization), and Kaplan Meier curve, considering statistically significant those results with a p<0.05. Sample of 99 patients, 18 in low risk group, 35 intermediate risk, 44 high risk and 2 very high risk. In terms of mortality, 7 deaths(high risk, 15.9%) and 2(very high risk, 100%), statistically significant (Fisher 17.07, p<0.0001). In terms of hospitalization days, median 7 days(low risk), 10(intermediate risk), 17 (high risk) and 5 (very high risk);statistically significant(F 6.37, p 0.001). In the survival analysis, median survival of 7 days(low-risk), 10(intermediate risk) and 19(high risk)(Log Rank 32.887, p<0.0001)(Fig 1). In conclusion, 4CMortality score is a good tool to establish the probability of poor evolution in asthmatic patients admitted for COVID-19 due to increased mortality and hospital stay.
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The aim of this study was to investigate how breast cancer follow-up in the Netherlands changed during the COVID-19 pandemic, compared to 2018-2019, and to what extent follow-up during the pandemic corresponded to the patient risk of recurrence. During the early phase of the pandemic the Dutch Society for Surgical Oncology (NVCO) issued a report with recommendations on how follow-up could be postponed, as a guidance for the pandemic, based on a low, intermediate or high risk of recurrence. In this study we investigated to what extent this advice was followed. A dataset of 33160 women diagnosed with primary invasive breast cancer between January of 2017 and July of 2021 was selected from the Netherlands Cancer Registry (NCR) and Dutch Hospital Data (DHD). The pandemic, 2020 and weeks 1-32 of 2021, was divided into six periods (A to F), based on the number of hospitalized COVID patients in the Netherlands. The five-year risk of locoregional recurrence (LRR) was determined for each patient with the INFLUENCE nomogram. The LRR risk was compared to the risk groups from the NVCO report with a Kruskal-Wallis test. The percentage of patients who received a mammogram during period A to F was compared to the same periods of 2018-2019 with a chisquared test. Correlation between the LRR risk, and if patients had a mammogram, was investigated with logistic regression. This analysis was repeated separately for the risk groups. Correlation between the LRR risk, and time intervals between surgery and the first and second mammogram was analyzed using cox proportional hazard models, this was also repeated for the risk groups. There was a significant difference in LRR risk between the NVCO risk groups. In the low-risk group (n=7673), 86 patients (1.1%) had a risk >5%. In the intermediate risk group (n=19197), 18364 patients (95.7%) had a risk of < 5%, and 65 patients (0.34%) had a risk of >10%. In the high-risk group (n=2674), 2365 patients (88.4%) had a risk < 10%. The percentage of patients who received a mammogram was significantly lower in periods B to F of the pandemic. Logistic regression showed a negative correlation between the risk of LRR and if patients had a mammogram in 2020 (OR 0.93) and 2021 (OR 0.93). There was also a negative correlation between the risk groups and mammography in 2020 (OR 0.92 for intermediate and 0.80 for high), and for the risk groups and mammography in 2021 (OR 0.98 for intermediate and 0.95 for high). There was no significant impact of LRR risk, or risk group, on time intervals between mammograms. During the pandemic, patients with a higher LRR risk, or a higher risk according to NVCO advice, had lower odds of having a mammogram. If the advice would have been followed, in 0.5% of the patients scheduled for follow-up, the recommendation was to postpone in contrast to a high estimation of the individual risk. For 62.7%, a follow-up was recommended, despite a low estimated individuals risk. Because the number of high-risk patients is relatively low, individual risk prediction could be supportive, in case of future restrictions. This way the high-risk patients can be identified and prioritized for follow-up, and can also be encouraged to come to the hospital.
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Background: Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this combination in the frontline setting, randomised phase 3 and real-world data are currently lacking. Aims: To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity profile of IBR +/-R in adult patients with previously untreated MCL. Methods: Following institutional approval, adults commencing IBR +/-R for untreated MCL under interim Covid-19 arrangements were prospectively identified by contributing centres. Hospital records were interrogated for demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT. Results: Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53 mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in 56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6), pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment. New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively. For the whole population and high-risk pts only, ORR was 74.4% and 64.7% respectively (p=0.2379), with a median time to response of 3.8m, coinciding with the first response assessment scan. Seven pts (16.7%), of whom 2 had highrisk disease, attained CR at a median of 6.0m. ORR for pts receiving vs not receiving R were 84.2% and 66.7% respectively (p=0.1904). IBR was discontinued in 20/61 pts (32.8%) at a median time to discontinuation of 4.1m, due to progressive disease (PD, 19.7%), toxicity (4.9%), death (3.3%;1 pt each of Covid-19 and E. coli infection), pt choice (3.3%) and other unspecified reasons (1.6%). 15/66 pts (22.7%) overall and 7/23 (30.4%) with high-risk disease progressed on IBR at a median time to PD of 4.0m. No pts underwent autologous stem cell transplantation consolidation during the study period. 12/57 pts (21.1%) received second line treatment (R-chemotherapy n=7, Nordic MCL protocol n=2, VR-CAP n=2, pirtobrutinib n=1). Response to second line treatment was CR in 4/11 pts, PD in 7/11. Of the 2 Nordic-treated patients, 1 had CR after cycle 2 and 1 PD. Fourteen pts (21.2%) died during the follow up period, due to MCL (n=11), Covid-19 (n=2) and congestive cardiac failure (n=1). Overall survival was lower for patients with high-risk disease (HR 0.55, p=0.038). Image: Summary/Conclusion: In this real-world UK cohort of pts receiving first-line IBR +/-R for MCL, including older and high-risk pts, we report high ORR rates in a similar range to the phase II Geltamo IMCL-2015 study of combination IBR-R in an exclusively low-risk population. Documented CR rates were lower, possibly reflecting a low usage of rituximab in the Covid-19 pandemic as well as CT assessment of response. Treatment was generally well tolerated, with low rates of toxicityrelated treatment discontinuation. The study is ongoing.
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Background: In the current global COVID-19 pandemic, terminal care in a patient's home has been expanded as a positive choice even for patients suffering from hematological malignancy (HM). Although there are many tools for predicting the prognosis of patients in the terminal phase of solid tumors, there is little information about prognostic factors in patients in the terminal phase of HM, especially patients receiving home medical care (HMC). In comparison to patients with solid tumors, those with HM are more likely to have acute diseases such as acute bleeding and acute infection leading to death. A previous report revealed that HM was a factor associated with aggressive end-of-life care. Because of the various complications associated with HM, it was reported to be difficult to predict the prognosis for patients with HM. Providing patients with accurate information about prognosis is important for them to consider how to spend their remaining life. Aims: In patients in the terminal phase of HM who received HMC, we aimed to validate the usefulness of two prognostic models: Palliative Prognostic Index (PPI), which is an established prognostic model for patients in the terminal phase of a solid tumor, and the prognostic model reported by Kripp et al., which is a prognostic model for patients with HM in a palliative care unit. In addition, we aimed to determine prognostic factors for patients in the terminal phase of HM who received HMC and to develop a more detailed prognostic scoring system. Methods: We retrospectively evaluated 136 patients in the terminal phase of HM who were receiving HMC provided by 6 clinics between 2008 and 2022. Medical records relevant to prognosis were collected by a chart review. The effects of possible factors associated with overall survival (OS) were determined by the Kaplan-Meier method and univariate and multivariate Cox regression models. This study was approved by the IRB of Hokkaido University Hospital. Results: Patients characteristics were as follows: male/female, 78/58;age, 25 to 94 years;median age, 79 years;AML, 50 patients;B-NHL, 32;MDS, 24;MM, 13;T-NHL 6;ALL, 5;ATL 2, CMML 2, and PV, 2. According to PPI, there was no significant difference in OS between the intermediate-risk group and the low-risk group (panel A;P = 0.15). By using the prognostic model reported by Kripp et al., we could stratify the patients into 3 risk groups with significantly different survival times (panel B;P < 0.01). However, there was a wide range of survival times in the high-risk group (OS, 0 to 125 days;median OS, 24 days). In our investigation of factors associated with OS, multivariate analyses revealed that there were 7 factors associated with poor OS (panel C). For the development of our prognostic scoring system, each variable was weighed according to the value of the hazard ratio (panel C) and 4 risk groups were shown to clearly discriminate survival (P < 0.01): low-risk group (n = 25, median OS of 434 days), intermediate-low risk group (n = 60, median OS of 112 days), intermediate-high risk group (n = 31, median OS of 31 days), and high-risk group (n = 20, median OS of 9 days). (Figure Presented ) Summary/Conclusion: This is the first investigation of prognostic factors that influence the overall survival of patients in the terminal phase of HM who received home medical care. In comparison to previously reported prognostic models, our scoring system could stratify patients in more detail. Providing patients and medical staff with accurate information about prognosis will lead to a higher quality of life in the terminal phase and better support by medical staff.
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Introduction/ Background: The global spread of SARS-CoV-2 and high demand for reagents may cause a challenge in procurement and the testing process, impacting turnaround times and the epidemiological data for optimal response mainly in low-income countries. To overcome this bottleneck, evaluating pooling system in the testing could be a solution Methods: For pooling strategy, 100 ul of each sample were pooled for up to 4 samples and extract using the same technology. The swabs were Oropharyngeal and nasopharyngeal swabs collected from individual attending clinic at Thies région and tested by Real-Time PCR after inactivation and RNA extraction using KingFisher Flex machine from ThermoFisher according to the manufacturer. SARS-CoV-2 detection were done using AllplexTM 2019-nCoV assay from Seegene targetting N, E, RdRp Gene in Biorad CFX96. All Samples are test individually and pooled. Ct values were compared between positives samples and result obtained with pooling. Results: We include in this analysis 43 pool of 4 samples each including 54 positive SARS-CoV-2 pooled with 114 negative samples and 40 pool of 4 negatives samples. Among positives sample included in the pool, 19 had Ct between 17 and 25, 23 between 25 to 30 and 12 had more than 30. Our result confirms that all 54 positives samples pooled in negatives samples were detected by pooling. The pooling was associated with a loss of 0.8 average of Ct ranging between -1.2 to 2.8. All samples individually negatives were also negatives in the pooling. The complete analysis is ongoing. Impact: This study indicates that pooling sample is practical and can be used for community surveillance, testing of low-risk populations, and in resourcelimited settings to mitigate reagent stock out. This can allow to reduce testing turnaround times and faster public health authorities' response to the global pandemic, especially in low-income countries. Conclusion: Our preliminary data confirms that pooling sample correctly identifies SARS-CoV-2 infected individual in 100% of our sample with an expected average of loss of ct of 0.8. This strategy can increase testing throughput in RLS and reduce turnaround time.
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RATIONALE: Bebtelovimab is a potent, fully human monoclonal antibody targeting the S-protein of SARS-CoV-2, with broad neutralizing activity to all variants of concern (including Omicron), based on non-clinical assays. This study aimed to evaluate the efficacy and safety of bebtelovimab alone (BEB) or together with bamlanivimab (BAM) and etesevimab (ETE) for the treatment of mild-tomoderate COVID-19, delivered via slow intravenous push.METHODS : This portion of the phase 2 BLAZE-4 trial (NCT4634409) enrolled 706 patients (between May and July 2021) with mild-tomoderate COVID-19 within 3 days of first laboratory diagnosis of SARS-CoV-2 infection. Patients at low-risk for severe COVID-19 were randomized 1:1:1 (double-blinded) to placebo, BEB 175 mg, or BEB 175 mg+BAM 700 mg+ETE 1400 mg (BEB+BAM+ETE). Patients at high-risk for severe COVID-19 were randomized 1:1 (open-label) to BEB or BEB+BAM+ETE;a subsequent treatment arm enrolled patients to BEB+BAM+ETE using CDC expanded criteria for high-risk. All treatments were administered intravenously over ≥30 seconds (open-label BEB) or ≥6.5 minutes (all other treatment arms). For the placebo-controlled population (termed low-risk), the primary endpoint was the proportion of patients with persistently high viral load (PHVL) (log viral load >5.27) on Day 7. For the open-label population (termed high-risk), the primary endpoint was safety outcomes and statistics were descriptive. RESULTS : Baseline sequencing data was available for 611 patients, 90.2% (n=551) aligned with a variant of interest or concern (WHO designation), with the majority infected with Delta (49.8%) and Alpha (28.6%) variants. For the low-risk population, active treatment arms had a numerically lower proportion of patients with PHVL compared to placebo, albeit not at a level of statistical signficance (see Table). Viral load-area under the curve analysis from baseline to Day 11 showed signficant reduction for patients treated with BEB compared to placebo. Time to sustained symptom resolution was significantly improved among patients who received BEB relative to placebo. As expected, the incidence of COVID-19-related hospitalization or all-cause deaths by day 29 were similar within the low-risk population. Overall, results were similar between patients in low-risk and high-risk populations receiving active treatment (see Table). The majority of treatment emergent adverse events (AEs) were mild-to-moderate in low-risk (n=36/380,9.5%) and high-risk patients (n=46/326,14.1%). Serious AEs were reported in 7/326 (2.1%) high-risk patients;none were reported in low-risk patients.CONCLUSION: The safety and efficacy data support the further development of bebtelovimab delivered via slow intravenous push of at least 30 seconds. (Table Presented).
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Blood transfusion is a vital service within modern healthcare. Patients expect to receive safe and quality assured blood as part of their clinical management. Globally, demand for blood has shown varying patterns, depending on the morbidity patterns, availability and access to healthcare with its determinants. In developed countries, an increasing emphasis on patient blood management, improved access to testing and technology assisted bloodless procedures, has gradually reduced the demand for blood. In the short term, the converse is expected in Low and middle income countries, with improving access to healthcare. The COVID19 pandemic has highlighted the vulnerabilities of blood transfusion services across the globe. Although much attention has been made to ensure safety of blood from the testing and processing aspects, there is a lack of focus on the source. According to the WHO Global Status Report on Blood Safety and Availability 2021 (in preparation), 86.7% of donations over the last decade has been from voluntary donations. Although most nations have stated policies that support voluntary blood donors, in many, there is no programmatic approach to promote awareness, motivate and retain the safe pool of donors, leaving it to fragmented local efforts. A clear understanding of baseline demographic profile, health status, prevalent morbidities, socio-cultural beliefs and practices is necessary to identify target groups and plan social marketing campaigns. Lack of reliable donor information can be overcome by creation of secure federated donor registries with authenticated donor identity management to enable systematic data collection. It will also help to plan donor engagement and recognition. Registries accessed and updated locally, with confidential sharing of information will also dissuade potential malpractice among blood donors. There is a need to normalize the conversation about blood donation in our communities. Increasing the availability of reliable information about the science of donation, safety and the use of blood is essential to overcome a lack of awareness. Public authorities can mandate display of information, in local languages, in public spaces and media. Individuals are motivated by a variety of reasons. Identifying and sustaining these can only be through careful systematic engagement. Though modern technologies such as social media, messaging platforms and apps have increasingly become popular, the actual extent of the impact of these have not been clearly documented. Direct interaction with individuals has shown good results. Facilities at blood donor drives, fixed donor centres and blood centres need to be carefully structured to enhance a pleasant donor experience while being regulated to ensure donor safety and quality. Donor health interventions including counselling and medical consults for deferred donors will help sustain the bond between the potential donor and the blood centre. Non-financial incentives such as weightage for voluntary donations during employment may be worth exploring. Retaining repeat voluntary donors from a low-risk population remains a challenge, which can be met only through sustained and systematic public investment and engagement with the community to change attitudes and participate in ensuring blood security and safe blood for all.
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Background - The WINDOW-1 regimen introduced first-line ibrutinib with rituximab (IR) followed by 4 cycles of R-HCVAD for younger mantle cell lymphoma (MCL) patients (pts) demonstrating 90% CR on IR alone and we aimed to improve the CR rate with the addition of venetoclax. We therefore investigated the efficacy and safety of IR and venetoclax (IRV) followed by risk-stratified observation or short course R-HCVAD/MTX-ARA-C as consolidation in previously untreated young patients with mantle cell lymphoma (MCL). Our aim was to use a triplet chemotherapy-free induction to reduce the toxicity, complications and minimize chemotherapy exposure in MCL pts. Methods - We enrolled 50 previously untreated pts in this single institution, single arm, phase II clinical trial - NCT03710772. Pts received IR induction (Part-1) for initial 4 cycles. Pts were restaged at cycle 4 and received IRV for up to eight cycles (Cycle 5 to Cycle 12) starting with ramp up venetoclax dosing in Cycle 5. All pts who achieved CR prior to cycle 12 continued to receive IRV for 4 cycles (maximum 12 cycles) and then moved to part 2. Pts were stratified into three disease risk groups: high, moderate and low risk categories from the baseline data for assignment to R-HCVAD/MTX-ARA-C as consolidation in part 2 (4 cycles, 2 cycles, or no chemotherapy for high, medium and low risk pts respectively). Briefly, low risk pts were those with Ki-67 ≤30%, largest tumor mass <3 cm, low MIPI score and no features of high risk disease (Ki-67 ≥50%, mutations in the TP53, NSD2 or in NOTCH genes, complex karyotype or del17p, MYC positive, or largest tumor diameter >5 cm or blastoid/pleomorphic histology or if they remain in PR after 12 cycles of part 1. Medium risk are pts which did not belong to low or high-risk category. Those who experienced progression on part 1 went to part 2 and get 4 cycles of part 2. Patient were taken off protocol but not off study, if they remained in PR after 4 cycles of chemotherapy, these patients were followed up for time to next treatment and progression free survival on subsequent therapies. After part 2 consolidation, all pts received 2 years of IRV maintenance. The primary objective was to assess CR rates after IRV induction. Adverse events were coded as per CTCAE version 4. Molecular studies are being performed. Results - Among the 50 pts, the median age was 57 years (range - 35-65). There were 20 pts in high-risk group, 20 pts in intermediate-risk group and 10 pts in low-risk group. High Ki-67 (≥30%) in 18/50 (36%) pts. Eighteen (36%) had high and intermediate risk simplified MIPI scores. Six (12%) pts had aggressive MCL (blastoid/pleomorphic). Among the 24 TP53 evaluable pts, eight pts (33%) had TP53 aberrations (mutated and/or TP53 deletion by FISH). Forty-eight pts received IRV. Best response to IRV was 96% and CR of 92%. After part 2, the best ORR remained unaltered, 96% (92% CR and 4% PR). The median number of cycles of triplet IRV to reach best response was 8 cycles (range 2-12). Fifteen pts (30%) did not receive part 2 chemotherapy, two pts (4%) received 1 cycle, 16 pts (32%) 2 cycles and 13 pts (26%) got 4 cycles of chemotherapy. With a median follow up of 24 months, the median PFS and OS were not reached (2 year 92% and 90% respectively). The median PFS and OS was not reached and not significantly different in pts with high and low Ki-67% or with/without TP53 aberrations or among pts with low, medium or high-risk categories. The median PFS and OS was inferior in blastoid/pleomorphic MCL pts compared to classic MCL pts (p=0.01 and 0.03 respectively). Thirteen pts (26%) came off study - 5 for adverse events, 3 for on study deaths, and 2 for patient choice, 2 patients lost to follow up and one for disease progression. Overall, 5 pts died (3 on trial and 2 pts died off study, one due to progressive disease and another due to COVID pneumonia). Grade 3-4 toxicities on part 1 were 10% myelosuppression and 10% each with fatigue, myalgia and rashes and 3% mucositis. One pt developed grade 3 atrial flutter on part 1. None had grade 3-4 bleeding/bruising. Conclusions - Chemotherapy-free induction with IRV induced durable and deep responses in young MCL pts in the frontline setting. WINDOW-2 approach suggests that pts with low risk MCL do not need chemotherapy but further follow up is warranted. This combined modality treatment approach significantly improves outcomes of young MCL pts across all risk groups. Detailed molecular analyses will be reported. (Figure Presented).
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Introduction: Management of coronavirus disease 2019 (COVID-19) requires accurate assessment of risk of future cardiopulmonary complications. Deep learning can extract complex relationships between medical imaging and clinical outcomes. Hypothesis: A deep learning model can predict 30-day mortality from COVID-19 based on a chest radiograph image. Methods: A deep learning model (CXR-CovRisk) was developed to estimate 30-day mortality risk using a single chest radiograph image (chest x-ray or CXR). The model was developed using 1,738 patients with PCR-confirmed coronavirus disease 2019 (COVID-19) from four Boston-area hospitals between March 1, 2020 and April 24, 2020. CXR-CovRisk was tested on 903 consecutive patients with confirmed COVID-19 between April 25, 2020 and June 15, 2020. CXR-CovRisk was compared to two published deep learning models (PXS and COVID-GMIC) and a clinical risk factor-based severity score for discrimination of 30-day mortality. The continuous risk score was converted to three risk groups: Low, Medium, and High based on development dataset probability quantiles. Results are provided for the independent testing set onlyResults: CXR-CovRisk had high discrimination for 30-day mortality (AUC = 0.839, 95% CI [0.79,0.89]), which was higher than when using a deep learning lung disease severity score (PXS AUC 0.750 [0.70,0.80], p < 0.001) or the output of a model trained for 96-hour mortality prediction (COVID-GMIC 0.755 [0.70,0.81], p = 0.003). CXR-CovRisk had added value to the clinical riskfactor based severity score (Clinical Severity Score AUC 0.799 [0.76,0.84] vs. Combined AUC 0.872 [0.84,0.90], p < 0.001). Among outpatients not admitted to the hospital, the CXR-CovRisk High-risk group had a high rate of subsequent hospital admission and 30-day mortality (composite event rate 11/26, 42.3%), higher than the medium-risk (30/179, 16.8%, p=0.005) and low-risk groups (17/172, 9.9%, p < 0.001). Conclusion: A deep learning model, CXR-CovRisk, can estimate 30-day mortality risk from a chest radiograph image.
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3,537 patients were scheduled and presented for routine elective endoscopic procedures at a single high-volume outpatient endoscopy center in Macon, Georgia for a period of 4 months starting on May 27, 2020. The center had reopened after a 2-month closure for the initial COVID-19 surge. The median age of patients in our cohort was 60 years, range 17-90 years 42% male, 58% female. No patients with respiratory symptoms, fever, acute GI symptoms, or COVID-19 exposure were scheduled without a prior negative PCR test, which was not otherwise routinely performed pre-endoscopy as this testing was not readily available and had a 3-7-day lag period for results and patient deterrent from the additional step. On arrival the day of the procedure, all patients had temperature and history screenings retaken. In addition, mask-wearing for staff and patients was mandatory, all patients receive an antiseptic oral rinse, and there was an upgraded plasma air filtration ventilation in place. All patients pre-procedure underwent rapid ten-minute antibody (Ab) testing with a Healgen COVID-19 IgG/IgM test (IgG negative and positive predictive value respectively (NPV, PPV) of 100% and 67.8% with estimated prevalence of 5% (FDA-EUA Authorized Serology Test Performance). On-site Ab testing requires a CLIA medium complexity designation. IgM positive patients underwent additional PCR testing. A total of 33 patients (0.94%) were Ab positive. Seven of these (0.20%) were IgG positive (71%M 29%F, median age 61). 6 of 7 IgG positive patients reported either a prior history of exposure or tested PCR positive in the preceding weeks;they were deemed safe for procedure. 26 were IgM positive or IgM/ IgG positive (0.74%;31%M, 69%F-median age 58);these were designated with potentially active infection and were not allowed to proceed with the procedure. PCR was performed within 24 hours on IGM groups. Of these, 6 had symptoms or exposure that had not been disclosed on screening (0.17%);3 of these were PCR positive. 20 were confirmed without any symptoms or contact exposure on repeated questioning (0.57%);8 of these were PCR positive. All procedure patients received a phone call 1 week following procedure and remained asymptomatic. Conclusion: This cohort represents a screened population deemed to represent a low-risk group. Universal Ab testing with a high NPV yielded 0.74% with potential active infection of which 42% were confirmed with PCR. A negative PCR in this group could not exclude active infection. 0.17% of patients falsely reported no exposure or symptoms. All infected individuals could have gone undetected and infected staff or others in the community. None of the staff at our center have been diagnosed with COVID-19 attributable to endoscopy center contact. Antibody testing may be an effective and low-cost adjunct to other safety measures at endoscopy centers.
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Introduction: Obinutuzumab-based induction immunochemotherapy was demonstrated to improve the outcome of patients with follicular lymphoma (FL) comparing to the regimens with rituximab in GALLIUM study (NCT01332968). The infusion related reactions (IRRs) occur in more than half of FL patients during the first obinutuzumab administration. Therefore, during the whole treatment period infusions lasting more than 3-4 hours are so far recommended. Shorter infusions would be more convenient for both patients and medical staff and could also contribute to the shorter hospitalization that is desirable during COVID-19 pandemic. The aim of the study was to evaluate the tolerance and early efficacy of obinutuzumab-based regimens in FL patients in clinical practice. Methods: We evaluated tolerability of obinutuzumab infusions and response rates to different regimens of chemotherapy combined with obinutuzumab in consecutive FL patients treated in hemato-oncology centers in Poland from Jan 2020 to Jan 2021. Obinutuzumab was combined with CHOP, CVP or bendamustine according to the treating physician choice. Obinutuzumab maintenance was offered to the patients who achieved at least partial response (PR) after induction immunochemotherapy. Response was evaluated with computed tomography or positron emission tomography according to 2014 Lugano criteria. Adverse events were assessed according to Common Toxicity Criteria (version 5). Results: The study group included 129 treatment-naive FL patients. The median age (range) was 52 (29 - 90) years, 35.7% of patients were males. According to FLIPI 46.5 % of patients were classified as high risk, 33.3% as intermediate and 20.2% as low risk, whereas 33.7%, 30.4% and 35.9% of patients were in PRIMA PI high, intermediate and low risk groups, respectively, Table 1. Median number of GELF criteria was 2 (range 1-6). Induction chemotherapy included: CVP in 48.1% (n=62), CHOP in 29.5% (n=38) and Benda in 22.5% (n=29) of patients. Median number of cycles was 6 (range 1 - 8). Maintenance was started in 85 patients (76.6%). The first obinutuzumab dose was administered as a single infusion during the first day of the first cycle in 43.4% of patients (n=56), whereas 56.6 % (n=73) of patients had initial infusion divided into 2 days (100 mg and 900 mg). During the first cycle 93.8% (n=121) of patients received three doses of obinutuzumab. The doses were omitted in 8 patients: in 4 due to Covid-19, in 1 due to pneumonia and neutropenia and in 3 cases due to neutropenia. IRRs were reported during the first Obinutuzumab administration in 10.1% of patients (n=13, grade 1/2 in 11 and grade 3 in 2 patients): in 7 patients who received obinutuzumab initial dose in single infusion and in 6 patients who received first obinutuzumab dose divided in two days. Median time of the first infusions was 4 hours and 55 min (range 1:30 - 9:45). There were no IRRs reported during the subsequent obinutuzumab infusions. The most common adverse event was neutropenia with grade 3/4 events reported in 51.1% of patients (n=66). G-CSF support was given in 70.4% (n = 81/115), and as the primary prophylaxis in 42.6 % (n=49) of patients. The SARS-CoV-2 infection occurred in 19 patients regardless of initial chemotherapy regimen. After induction immunochemotherapy complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) rates were: 71.8%, 23.9%, 0.9% and 3.4%, respectively, Table 2. With a median follow up of 8.7 months 5 patients (3.9%) relapsed, 4 died due to COVID infection. There were no deaths caused by FL. Conclusions: In our study obinutuzumab-based induction treatment was well tolerated. The low incidence and low grade of infusion related reactions in most of the patients, reported only during the first infusion, support the practice of administration of the first obinutuzumab dose in a single infusion. For convenience, the concept of short, 90 minutes infusion of Obinutuzumab starting from the second cycle could be considered (Canales MA, EHA 2021). During COVID-19 pandemic using obinutu umab with chemotherapy is feasible and justified by the high response rate to this treatment. [Formula presented] Disclosures: Paszkiewicz-Kozik: Roche: Honoraria, Other: congress fee;Servier: Other: congress fee;gillead: Other: travel grant;Takeda: Honoraria, Other: Travel Grants. Hus: Astra Zeneca: Honoraria, Research Funding;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees. Romejko-Jarosinska: roche: Other: congress fee;servier: Other: congress fee;gilead: Other: traver grant. Drozd-Sokolowska: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka: Janssen: Consultancy, Research Funding;Roche: Consultancy, Research Funding, Speakers Bureau;Servier: Consultancy, Speakers Bureau;Acerta Pharma: Research Funding;AbbVie: Research Funding;Macrogenics: Research Funding;Beigene: Research Funding;MEI Pharma: Research Funding;Incyte Corp.: Research Funding;Takeda: Research Funding. Lech-Marańda: Amgen: Membership on an entity's Board of Directors or advisory committees;Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding;Roche: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees. Walewski: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Amgen: Consultancy, Honoraria;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS: Consultancy, Honoraria;Celgene: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Servier: Consultancy, Honoraria.
ABSTRACT
Background: The management of acute myeloid leukemia (AML) patients usually requires long inpatient treatments that can affect the limited care facilities, the quality of life, and increases healthcare costs. Additionally, leukemia treating centers in developing countries face limited sources to deliver high-dose chemotherapies as inpatient treatments. Therefore, several reports have established the feasibility and safety of outpatient consolidation. We aimed to implement a high-dose cytarabine outpatient program for AML in a limited-source institution at a public center in Peru.Methods: We conducted a prospective pilot study starting in January 2019 and ending before the COVID-19 Pandemic in March 2020. Eligible patients were ≥ age 14, met inclusion criteria for inpatient induction regimens, were without active infection, and had the following: normal chest x-ray and biochemistry, complete remission after one cycle of 7+3 induction. Logistical requirements included a 3-hours distance residence near the treatment center, caregiver support, trained nursing staff, infusion room capacity, and participation in follow-up. Patients received prophylactic antimicrobials such as oral levofloxacin, fluconazole, and acyclovir and were admitted to the hospital for predetermined complications of therapy (fever, G3-4 toxicity, febrile neutropenia, bleeding or refractory thrombocytopenia). Risk stratification was based on conventional cytogenetics and multiplex PCR using Leukemia.net criteria. Results: Forty-two patients were included during the study period. The median age was 38 years (16-63) and Female/Male ratio 4:3. According to Leukemia.net, 24% were classified as high, 50% intermediate and 26% as low risk group. Including FLT3 mutations in 26% of cases. Twenty-two and 20 subjects received 1-2 and 3-4 cycles of ambulatory HiDAC, respectively. About one-third of cases had emergency admissions during consolidation and 74% complete at least 3 cycles of cytarabine. Only 4 patients underwent sibling-donor allo-SCT. Sixty-four percent experienced relapses, and at 2 years follow-up only 21 subjects were alive. Median OS was 15 months, a better survival was shown among patients who received 3-4 cycles of ambulatory HiDAC (2-year OS 18 vs 23%, p=0.031). Conclusion: Our pilot study shows the feasibility to deliver HiDAC as outpatient consolidation in selected AML cases in a limited setting. Additionally, a high rate of relapses and poor survival was noted in our cohort that requires further consideration. Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Background: Rapid Access Chest Pain Clinic (RACPC) is a vital service in many hospitals in the UK, providing early specialist input for patients with suspected coronary artery disease referred via the Emergency Department (ED) or primary care (1). When the COVID-19 pandemic forced hospitals to refine their outpatient systems (2), our Trust continued the RACPC service remotely via telephone consultations. Purpose: To examine the long-term viability of this service, we designed a study to compare the outcomes of patients seen remotely during the pandemic to patients seen face to face. Methods: We performed a retrospective cohort study. The remote group (n=217) were patients seen over 4 weeks in April 2020, all having telephone consultations. The control group (n=368) were patients assessed face to face in the same 4-week period in 2019. Outcomes being analysed included: mode of investigation;interventions performed;and a 12 month combined safety endpoint of ED attendance with chest pain, re-referral to cardiology and hospitalisation for cardiac issue. Subgroup analysis was performed based on typicality of symptoms defined by NICE (3). Results: Baseline characteristics were similar between groups. In both 2019 and 2020, the largest subgroup of patients were those with nonanginal chest pain (64%, 71%). There were significant differences in investigation and management between the two cohorts (Figure 1). In 2020, a higher proportion of patients were discharged with no investigation (57% vs 23%, p<0.0001). This was driven primarily by changes in management of patients with non-anginal chest pain. There were significantly higher rates of investigation of this subgroup in 2019 by either CT Coronary Angiography (25% versus 4.5%, p<0.001) or functional testing (25% versus 6.5%, p<0.001), with a much higher rate of reassurance and discharge in 2020 (81% versus 36%, p<0.0001). More patients received coronary intervention in 2019 than in 2020 (2.4% vs 0%, p=0.02). In 2020, higher proportions of patients were commenced on medical therapy without further investigation when presenting with atypical (28% versus 1%, p<0.0001) or typical angina (63% versus 11.4%, p<0.0001) (Figure 2). There was no significant difference in the 12 month combined safety endpoint (1.3% in 2019 versus 2.3% in 2020, p=0.39), and no reported cardiac deaths. Conclusions: During the pandemic, as expected, fewer patients were investigated for coronary artery disease, with the preference being to commence medical therapy initially. This did not have a significant effect on safety endpoints. Importantly, clinicians felt comfortable with assessing and discharging patients with non-anginal chest pain remotely in 2020. This is key to the viability of a remote RACPC model, as this subgroup forms the majority of the referrals. We suggest that RACPC is appropriate for a remote model in the long term, in view of the relatively low-risk population and clear management guidelines.
ABSTRACT
This work examines a mathematical model of COVID-19 among two subgroups: low-risk and high-risk populations with two preventive measures; non-pharmaceutical interventions including wearing masks, maintaining social distance, and washing hands regularly by the low-risk group. In addition to the interventions mentioned above, high-risk individuals must take extra precaution measures, including telework, avoiding social gathering or public places, etc. to reduce the transmission. Those with underlying chronic diseases and the elderly (ages 60 and above) were classified as high-risk individuals and the rest as low-risk individuals. The parameter values used in this study were estimated using the available data from the Johns Hopkins University on COVID-19 for Brazil and South Africa. We evaluated the effective reproduction number for the two countries and observed how the various parameters affected the effective reproduction number. We also performed numerical simulations and analysis of the model. Susceptible and infectious populations for both low-risk and high-risk individuals were studied in detail. Results were displayed in both graphical and table forms to show the dynamics of each country being studied. We observed that non-pharmaceutical interventions by high-risk individuals significantly reduce infections among only high-risk individuals. In contrast, non-pharmaceutical interventions by low-risk individuals have a significant reduction in infections in both subgroups. Therefore, low-risk individuals' preventive actions have a considerable effect on reducing infections, even among high-risk individuals.