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Study objective. It has been shown that human common viruses are new target genes for host cell dioxin receptor transcriptional (AhR-ARNT) complex initially proven to up-regulate mammalian genes containing dioxin-response elements (DRE) in the promoters [doi:10.1016/j.ijid.2012.05.265]. Initially, transactivation of HIV-1 and HBV by 2,3,7,8-tetrachlodibenzop- dioxin (TCDD) at low nanomolar range was demonstrated [doi:10.3109/00498259309057034]. Noteworthy, transactivation of human cytomegalovirus (CMV) was shown with 0.3 ppt dioxin, i.e. lower than its current background level in the general population (~3.0 ppt). Recently, reactivation of CMV infection was found to influence worse clinical outcome following SARS-CoV-2 infection (doi: 10.1186/s12979-020- 00185-x). Other findings showed that CMV and herpes simplex virus 1 (HSV-1) reactivation were observed in immunocompetent patients with COVID-19 acute respiratory distress syndrome (ARDS) (doi.org/10.1186/s13054-020-03252-3). Addressing occurrence of Herpesviridae reactivation in severe COVID-19 patients, and still unspecified real triggers of CMV and HSV-1 reactivations, we tested TCDD, which current body burden (DBB) ranges from 20 pg/g (TEQ in fat) in general population to 100 pg/g in older people. Methods. In Silico quantitation of active DRE in promoters of viral genes. Virus DNA hybridization assay. Clinical and epidemiological analyses. Results and Discussion. In this study, a computational search for DRE in CMV and HSV-1 genes was performed by SITECON, a tool recognizing potentially active transcriptional factor binding sites. In silico analysis revealed in regulatory region of CMV IE genes from 5 to 10 DRE, and from 6 to 8 DRE in regulatory region of HSV-1 IE genes.We established that a low picomolar TCDD can trigger up-regulation of CMV and HSV-1 genes via AhR:Arnt transcription factor in macrophage(doi.org/10.1016/ j.ijid.2012.05.265) and glial human cell lines (doi.org/10.1016/j. jalz.2016.06.1268), respectively. In fact, viral reactivation may be triggered in COVID-19 ARDS patients by higher pulmonary TCDD concentrations, because "lipid storm" within lungs of severe COVID-19 patients has been recently reported (doi.org/ 10.1101/2020.12.04.20242115). TCDD is known as the most potent xenobiotic, which bioaccumulates and has estimation half-life in humans of up to 10 yr. Due to hydrophobic character (Log P octanol/water: 7.05), TCDD partitions into inflammatory lipids in lung tissue thus augmenting its local concentration. Population-based epidemiological data on SARS-CoV-2 first wave of pandemic revealed high level of CMV seropositivity and cumulative mortality rate 4.5 times in Lombardi region of Italy, where after Seveso industrial accident TCDD plasma level in pre-exposed subjects is 15 times the level in rest of Italy (doi. org/10.3389/fpubh.2020.620416). Also, Arctic Native (AN) peoples consume dioxin-contaminated fat in seafood and have TCDD DBB, i.e. 7 times that in general population. To the point of this paper, their COVID-19 mortality is 2.2 times of that among non-AN Alaskans (doi: 10.15585/mmwr.mm6949a3). Conclusion(s): TCDD in the picomolar range may trigger CMV expression in lung cells and commit virus to the lytic cycle, which can be applied to reactivation of Herpesviridae infection in immunocompetent patients with COVID-19 ARDS syndrome.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Background: Use of home spirometry to monitor lung function has been increasing in popularity in persons with cystic fibrosis (PwCF) since the start of the COVID-19 pandemic. Although clinic spirometry is interpreted from validated standards, expected test-to-test variation of home spirometry and how variation during baseline health may relate to clinical changes are unknown. The aim of this study was to determine variation in baseline lung function during daily home spirometry and identify associations with clinical outcomes. Method(s): Subjectswere selected based on available spirometry data from a cohort of PwCF enrolled in a long-term airway microbiome study. Subjects were provided with a PiKo-6 hand-held spirometer (nSpire Health, Inc., Longmont, CO) and asked to perform spirometry maneuvers three times per. Validity of home spirometry (percentage predicted forced expiratory volume in 11 second (FEV1pp)) was compared with that clinic spirometry using Bland-Altman plots. Spirometry acceptability across multiple maneuvers in the same day was assessed using the American Thoracic Society (ATS) guidelines, with grade A or B (two or more maneuvers within 150 mL) considered acceptable. Variation in FEV1pp was assessed by calculating a mean FEV1pp and coefficient of variation (CoV). The association between CoV and pulmonary exacerbations (PEx) was tested using Cox proportional hazards regression models. Result(s): Thirteen subjects (62% female) with a mean age of 28.7 +/- 8.3 and mean FEV1pp of 59.9 +/- 8.2%were included. Median study durationwas 377 days (range, 33-730 days). Subjects used the home spirometer on average 51.2% of the study days (range 15-97%). On average, 58.9% of subjects (range 12-100%) used the home spirometer at least twice aweek, and 76.8% (range 65-100%) at least once aweek. To focus on periods of baseline health, days associated with PEx (spirometry performed 2 weeks before and during times of antibiotic therapy) were excluded. A median of 204 days (range 11-728 days) of baseline spirometry readings was available for further analysis. Comparing validity of home spirometry with that of clinic spirometry, Bland-Altman plots demonstrated overall good agreement with a slight bias (+0.042 L) toward higher readings for clinic FEV1pp (95% limits of agreement, -0.11-0.19 L). Spirometry quality was graded as acceptable on most study days (mean 90.6 +/- 4.6%) in which two or more maneuvers were recorded. Intra-individual variation in baseline FEV1pp was high, with a mean variation of 17.6 +/- 5.9% day to day and 15.2 +/- 6.2% week to week. Neither rates of acceptable spirometry grades nor CoV was associated with lung disease severity. Of the 13 subjects, 10 experienced one or more PEx, for a total of 32 PEx during the study. CoV was not associated with time to first PEx (hazard ratio [HR], 0.78;95% confidence interval [CI], 0.51-1.21;p = 0.24) or time to subsequent PEx (HR, 0.91;95% CI, 0.73-1.12;p = 0.28) during the study. Conclusion(s): Although home spirometry has generally good validity and acceptability, variation in lung function during baseline health is present and often exceeds expected variation in clinic spirometry per ATS standards. Variability may represent normal physiological variation or be related to the home spirometer itself or other factors but did not portend upcoming PEx. Recognition of variation during baseline health provides important context for interpretation of home spirometry.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Introduction: Prior to 2021, impalpable tumours in our unit were localised with Somatex wires. During the COVID pandemic we introduced Magseed due to its logistical advantages in allowing surgery on a site distant from our breast unit. We wanted to ensure our clinical outcomes with this new system were equivalent to those using wire localisation. Method(s): Electronic records for the first 50 consecutive Magseed localised wide local excisions and the preceding 50 consecutive wire localised wide local excisions were compared. Excision biopsies, palpable lesions, bracketed lesions and post neoadjuvant treatment patients were excluded. Patient demographics, tumour size, inadequate radial margin involvement rate, reoperation rate for margins, specimen weight, number of cavity shaves and operative time were recorded. [Formula presented] Results: Results are shown in table 1. There were no preoperative differences in the two groups. There were no significant differences in outcomes between the two groups, with a trend towards lower margin involvement rates but more shaves in the Magseed group. The mean operative time was slightly shorter in the Magseed group despite more axillary procedures being performed in this group. Conclusion(s): The change to the Magseed system led to logistical advantages with patient outcomes at least equivalent to wire guided excision.Copyright © 2023
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Background: Late presentation to care remains a major public health problem in Brazil, despite the countrys longstanding commitment to universal access to ART to all PLWH. The COVID-19 pandemic severely hit the country and further impacted the HIV care continuum, with worse disparities observed by gender and sexual orientation. By December 28th 2022, Brazil reported 10,493 and 14 mpox cases and deaths ranking second globall. Although mpox lethality is low, HIV-related immunosuppression may negatively impact mpox outcomes, increasing hospitalizations and fatalities. We aim to describe mpox hospitalization rates and explore the impact of HIV-infection on mpox-related hospitalizations and clinical outcomes. Method(s): Prospective, observational cohort study of individuals with confirmed mpox infection followed at the major mpox referral center in Rio de Janeiro, Brazil. Demographic and clinical data including reasons for hospitalization were systematically collected. Chi-squared or Fisher's exact tests for qualitative variables and the Moods median test for quantitative variables were used. Result(s): From June 12 to December 12, 2022, 402 participants had a laboratory-confirmed mpox diagnosis. Median age was 34 years, 365 (91%) were cisgender men, and 197 (49%) were PLWH. Overall, 39 (10%) participants were hospitalized due to mpox-related causes;20 (51%) were PLWH. All PLWH with CD4 counts< 200 cells/mm3 required hospitalization. Compared to nonhospitalized PLWH, a higher proportion of hospitalized PLWH had concomitant opportunistic infections (4/20 [20%] vs. 1/177 [0.6%];p< 0.001), were not virologically suppressed (7/20 [35.0%] vs. 22/177 [15.3%];p=0.1) and were not on ART (4/20 [20%] vs. 15/177 [7.6%];p=0.03). Among all hospitalized participants, PLWH were more frequently hospitalized due to severe proctitis than HIV-negative participants (12/20 [60%] vs. 5/19 [26.3%];p=0.03), with no differences regarding hospitalizations for pain control (Table). PLWH accounted for all cases of hospitalized individuals who required intensive care support (n=4), had deep tissue involvement (n=3) and had a mpox related death (n=2). Conclusion(s): Our findings suggest an association between worse outcomes in the HIV care continuum and mpox-related hospitalizations. Advanced immunosuppression (CD4< 200) contributed to more severe clinical presentations and death. Public health strategies to mitigate HIV late presentation and the negative impact of the COVID-19 pandemic to the HIV care continuum are urgently needed. Sociodemographic and clinical characteristics of mpox cases according to HIV and hospitalization status.
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Objective: To explore the predictive value of the duration of positive SARS‐CoV‐2 nucleic acid test in patients with coronavirus disease 2019 (COVID‐19) on clinical outcome. Methods: A total of 128 COVID‐19 patients admitted to Renmin Hospital of Wuhan University from March 2020 to May 2020 were selected and received symptomatic treatment. According to the clinical outcome of the patients, they were divided into a cured group (88 cases) and a death group (40 cases). The gender, age, time from onset to first diagnosis, clinical manifestations, past history, chest CT manifestations, respiratory support methods, blood gas indexes, the first laboratory test result after admission, and the duration of nucleic acid positive were compared between the two groups. Multivariate logistic regression analysis was used to determine the influencing factors of the clinical outcome of patients, and the ROC curve for each index was drawn to predict the clinical outcome of COVID‐19 patients. Results: Statistically significant difference between cure group and death group was found in age, arterial oxygen partial pressure, blood oxygen saturation, white blood cell count, neutrophil count, lymphocyte count, platelet count, urea nitrogen, blood potassium, D‐dimer, lactic acid, serum IL‐10, TNF‐α, and nucleic acid positive duration (P<0. 05). Multivariate logistic regression analysis showed that arterial blood oxygen partial pressure (OR=0. 602, 95%CI: 0. 411 ‐ 0. 882), lymphocyte count (OR= 0. 710, 95%CI: 0. 534 ‐ 0. 944), blood potassium (OR=2. 166, 95%CI: 1. 223 ‐ 3. 836), lactic acid (OR=2. 675, 95%CI: 1. 311 ‐ 5. 458), and nucleic acid positive duration (OR=1. 894, 95%CI: 1. 248‐2. 874) were the influencing factors of the clinical outcome of patients (P<0. 05). The areas under the ROC curve of lactate, arterial partial pressure of oxygen, nucleic acid positive duration, blood potassium, and lymphocyte count to predict the clinical outcome of patients were 0. 922 (95%CI: 0. 8867 ‐ 0. 968) and 0. 897 (95%CI: 0. 837 ‐ 0.957), 0.854 (95%CI: 0. 778 ‐ 0. 931), 0. 731 (95%CI: 0. 637‐0. 826), and 0. 704 (95%CI: 0. 608‐0. 812), respectively, which showed higher predictive value, and their best cut‐off values were 3. 35 mmol/L, 62 mmHg, 31 d, 4. 22 mmol/L, and 0. 91×109/ L, respectively, the sensitivities were 0. 914, 0. 906, 0. 844, 0. 750, and 0. 711, respectively, and the specificities were 0. 766, 0. 797, 0. 813, 0. 836, and 0. 820, respectively. Conclusion: Arterial partial pressure of oxygen, lymphocyte count, blood potassium, lactic acid, and nucleic acid positive duration are the influencing factors for the clinical outcome of COVID‐19 patients, and have a high predictive value for the death of the patients. © 2022 Editorial Board of Medical Journal of Wuhan University. All rights reserved.
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Introduction/Aim: COVID-19 has fast-tracked changes to healthcare delivery, including the introduction of a broad range of telehealth services. Work is needed to assess the ongoing suitability of telemedicine for the post-pandemic era. We sought to explore perceptions of telemedicine amongst patients and providers (clinicians and health administrators) who had appointments in cardiology, respiratory, neurology, rheumatology and gastroenterology services in hospital specialist outpatient clinics in Sydney Local Health District. Method(s): Semi-structured interviews explored perceptions of consultations undertaken virtually compared to in-person, seeking perspectives on the benefits, limitations and risks of outpatient telemedicine consultations. The 37 participants comprised 16 patients, 14 specialists, 3 Clinical Nurse Consultants and 4 administrators. Result(s): Patients indicated satisfaction with telemedicine consultations, especially during the pandemic. They valued saving on travel time and costs, and being able to access care from their homes, thereby minimising risk of COVID exposure. The chief disadvantage perceived by patients was inability to receive a physical examination. They noted greater challenges for people with hearing and visual impairments, limited digital skills and/or computer access. Providers' perceptions were more ambivalent. Although telehealth was understood to help meet demands during the pandemic, mis- and under-diagnoses were considered major concerns arising from the inability to perform physical examination. Most regarded telemedicine as an effective tool for review appointments but mentioned an associated increased workload. All participants mentioned the need for relevant education and training, better integration of telemedicine platforms into existing infrastructure and the need for a hybrid model of care. Conclusion(s): Telemedicine played a unique role in meeting patients' needs during the pandemic and its convenience was valued by patients. Clinicians expressed concerns about missed diagnoses, uncertain clinical outcomes, lack of administrative and technological infrastructure. The ultimate test of telemedicine will be its impact on clinical outcomes versus longstanding models of in person care.
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Background: The benefits of physical training on exercise capacity, pulmonary functioning, and health-related quality of life for people with cystic fibrosis (CF) is well documented [1], meaning it is currently considered part of standard CF care to encourage a physically active lifestyle [2,3]. COVID-19 limited opportunities for people with CF to undergo structured exercise programs in the hospital, gym, or leisure center. To address this, we launched three progressive on-demand exercise programs on Beam (a specialist online exercise, education and wellbeing platform for the CF community, www.beamfeelgood.com) aimed at varying disease severity and baseline fitness levels. Each 12-session program was curated by a CF physiotherapist and designed to build strength and cardiovascular fitness, improve CF symptom management, and increase confidence to exercise. Participants were offered remote coaching to support completion of the program, including email and text support, and joint workouts. Here,we look at the impact of this program on self-reported measures of health and exercise perceptions. Method(s): Adults with CFwere invited via social media to participate in one of three Getting Started exercise programs on Beam. Participants selfselected the program that was most suited to them based on their disease severity and current fitness levels, as outlined in Table 1. Participants were asked to complete pre- and post-program surveys evaluating their general health, emotional wellbeing, appetite, sleep, motivation, enjoyment, confidence, and time and limitations to exercise on a five-point scale. Result(s): Between November 2021 and March 2022, of 71 people signed up for a Getting Started program, 36 completed a minimum of one class, and 16 completed the entire 12-sessions in a program. Of the 16 who(Table Presented) Audience and aims of the three Beam programs completed a program, 75% felt more motivated, 68% felt fitter, 75% felt stronger, and 65.5% were happier. All said their enjoyment of exercise was the same or more than before (37.5% saying they enjoyed it more), and 43.7% said they became more confident. No adverse events were reported. Conclusion(s): This work suggests that CF-specific online exercise programs have the potential to increase strength and cardiovascular fitness levels as well as motivation, confidence, and enjoyment to exercise in adults with CF, although these outcomes were self-reported, and a research trial to evaluate impact on clinical outcome measures is warranted. Additionally, further research and service development is required to improve the programs and increase activation and completion of the exercise programs with greater consideration of behavior change interventions.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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BACKGROUND: The pathogenesis of angioedema induced by angiotensin-converting enzyme inhibitors is based on the accumulation of bradykinin as a result of angiotensin-converting enzyme blockade. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 receptor, which may inhibit its production and thereby lead to an increase in bradykinin levels. Thus, SARS-CoV-2 infection may be a likely trigger for the development of angioedema. AIMS: This study aimed to analyze cases of hospitalizations of patients with angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers during the coronavirus disease 2019 (COVID-19) pandemic. MATERIALS AND METHODS: This study retrospectively analyzed medical records of patients admitted to the Vitebsk Regional Clinical Hospital between May 2020 and December 2020 with isolated (without urticaria) angioedema while receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In all patients, smears from the naso and oropharynx for COVID-19 were analyzed by polymerase chain reaction. RESULT(S): Fifteen inpatients (9 men and 6 women) aged 44-72 years were admitted because of emergent events, of which 53.6% had isolated angioedema. In two cases, a concomitant diagnosis of mild COVID-19 infection was established with predominant symptoms of angioedema, including edema localized in the face, tongue, sublingual area, and soft palate. All patients had favorable disease outcomes. CONCLUSION(S): Patients with angiotensin-converting enzyme inhibitor-induced angioedema may require hospitalization to monitor upper respiratory tract patency. There were cases of a combination of angiotensin-converting enzyme inhibitor-induced angioedema and mild COVID-19. Issues requiring additional research include the effect of SARS- CoV-2 infection on the levels of bradykinin and its metabolites, the triggering role of COVID-19 in the development of angioedema in patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, recommendations for the management of patients with angiotensin-converting enzyme inhibitor-induced angioedema, and a positive result for COVID-19.Copyright © 2020 Pharmarus Print Media All rights reserved.
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Introduction: We aimed to describe the incidence, risk factors, and clinical outcomes of bacterial and fungal co-infections and superinfections in intensive care patients with COVID-19 in a retrospective observational study. Method(s): A retrospective cohort of intensive care patients with confirmed SARS-CoV-2 by PCR was analysed from January to March 2021. This was contrasted to a control group of influenza-positive patients admitted during 2012-2022. Patient demographics, microbiology and clinical outcomes were analysed. Result(s): A total of 70 patients with confirmed SARS-CoV-2 were included;6 (8.6%) of 70 had early bacterial isolates identified rising to 42 (60%) of 70 throughout admission. Blood cultures, respiratory samples, and urinary samples were obtained from 66 (94.3%), 18 (25.7%) and 61 (87.1%) COVID-19 patients. Positive blood culture was identified in 13 patients (18.6%). Bacteraemia resulting from respiratory infection was confirmed in 3 cases (all ventilator-associated). Line-related bacteraemia was identified in 9 patients (6 Acinetobacter baumannii, 4 Enterococcus spp. and 1 Pseudomonas aeruginosa and 1 Micrococcus lylae). No concomitant pneumococcal, Legionella or influenza co-infection was detected. Invasive fungal infections with Aspergillus spp. were identified in 2 cases. Pneumococcal coinfections (7/68;10.3%) were identified in the control group of confirmed influenza infection;clinically relevant bacteraemias (6/68;8.8%), positive respiratory cultures (15/68;22.1%). The rate of hospital- acquired infections was 51.4% for COVID-19 and 27.9% for influenza. Longer intensive care stay, type 2 diabetes, obesity and hematologic diseases were independent risk factors for superinfections in the COVID-19 cohort. Conclusion(s): Respiratory coinfections occurred in influenza but not in COVID-19 patients. The rate of hospital-acquired infections (51.4% for COVID-19;27.9% for influenza) was unexpectedly high in both groups.
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Introduction: Since March 2020, a number of SARS-CoV-2 patients have frequently required intensive care unit (ICU) admission, associated with moderate survival outcomes and an increasing economic burden. Elderly patients are among the most numerous, due to previous comorbidities and complications they develop during hospitalization [1]. For this reason, a reliable early risk stratification tool could help estimate an early prognosis and allow for an appropriate resources allocation in favour of the most vulnerable and critically ill patients. Method(s): This retrospective study includes data from two Spanish hospitals, HU12O (Madrid) and HCUV (Valencia), from 193 patients aged > 64 with COVID-19 between February and November 2020 who were admitted to the ICU. Variables include demographics, full-blood-count (FBC) tests and clinical outcomes. Machine learning applied a non-linear dimensionality reduction by t-distributed stochastic neighbor embedding (t-SNE) [2];then hierarchical clustering on the t-SNE output was performed. The number of clinically relevant subphenotypes was chosen by combining silhouette and elbow coefficients, and validated through exploratory analysis. Result(s): We identified five subphenotypes with heterogeneous interclustering age and FBC patterns (Fig. 1). Cluster 1 was the 'healthiest' phenotype, with 2% 30-day mortality and characterized by moderate leukocytes and eosinophils. Cluster 5, the severe phenotype, showed 44% 30-day mortality and was characterized by the highest leukocyte, neutrophil and platelet count and minimal monocytes and lymphocyte count. Clusters 2-4 displayed intermediate mortality rates (20-28%). Conclusion(s): The findings of this preliminary report of Eld-ICUCOV19 patients suggest the patient's FBC and age can display discriminative patterns associated with disparate 30-day ICU mortality rates.
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Background: Coronavirus Disease 2019 (COVID-19) pandemic disrupted routine program implementation worldwide with significant impact on quality and extent of technical oversight of implementation. Diverse digital reporting solutions and online meetings were some strategies designed to bridge program implementation supervision and reporting gaps worldwide. This paper evaluates usefulness and efficiency of digital solutions deployed by USAIDNigeria to ensure adequate oversight to sustain access and reporting of HIV viral load (VL) services Methods: To promote accountability and encourage peer-to-peer review and learning among USAID Implementing Partners, daily reporting via digital platforms and virtual weekly peer-review meetings were introduced. This enabled USAID team to monitor IPs' performance at health facilities and during community VL drives against set targets of 100% and 95% patient VL coverage and suppression (VLC/S) respectively. The platforms include National Laboratory Information Management System, remote sample login and Googlebased VL Status and Daily Lab Performance dashboards. This study assesses uptake of VL services and clinical outcomes in 16 states of Nigeria between October2019 through March2021 during various levels of COVID-19 lock down. Chi Square test was used to compare the pre-COVID (October2019-March2020), during lockdown (April2020-September2020) and post-COVID lockdown (October2020-March2021) performances at 95 confidence interval and < 0.05 level of significance. Result(s): Significant improvements in VL indicators were reported among eight USAID partners across 16 states. Pre-COVID, 591,906 clients on treatment were eligible for VL monitoring, 455,099 were tested and had documented VL results with a 76.9% and 89% VLC/S. During-COVID lockdown, 685,915 became eligible for VL monitoring, 531,371 had documented VL results, with 77.5% and 90% VLC/S. VLC/S increased to 93% each post-COVID lockdown, when 771,149 had documented VL out of 833,463 eligible. There was a significant increase number of clients on treatment who became eligible for VL test and had documented VL results and suppression from pre- during-COVID, and post-COVID lockdown (p=0.001) Conclusion(s): Digital solutions deployed by USAID were instrumental to sustaining service delivery with significant growth in access and efficiency to HIV VL services in 16 States in Nigeria despite impact of COVID-19. Program managers should continue to explore cost-efficient innovative approaches for program oversight.
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Background: Monitoring of HIV-infected individuals on antiretroviral treatment requires periodic viral load(VL) measurements to ascertain adequate response to treatment. While plasmaVL is widely available in health facilities, it is difficult for use among key populations(KPs) due to their high mobility and sophisticated sample storage and transport requirements, which are not available for community VL sample collection. Use of Dried Blood Spot(DBS) VL measurement has shown promise as an alternative to plasma specimens for KPs. Studies to investigate the performance of DBSVL quantification against the standard plasma VL assay has proven to be within acceptable range. DBSVL was introduced for sample collection among KPs when it became difficult to safely and appropriately collect, store and transport samples during COVID-19 lockdown. This study assessed the usefulness of the use of DBSVL deployed by USAID to ensure access to HIV VL services among KPs in 7 states of Nigeria during COVID-19 lockdown Methods: To mitigate the impact of COVID-19 lockdown, virtual trainings were conducted for one-stop-shops and community VL champions of USAID partners providing KPs services in seven states of Nigeria on DBS sample collection, storage and transportation and remote test ordering was activated for service providers. Standard operating procedures and job aids were deployed to points of service and laboratory equipment were verified for DBSVL testing. VL sample collection rate(SCR), VL coverage(VLC), VL suppression(VLS), turnaround time (TAT) and cost savings for the program between March2019 and February2021 were compared using the two-sample independent t test pre-COVID (March2019- February2020) and during-COVID lockdown (March2020 -February2021) at 95 confidence interval and < 0.05 level of significance. Result(s): There was a significant increase (p< 0.05) in SCR from 73% to 94%, VLC 44% to 85%, and VLS 78% to 95% pre-COVID to during-COVID respectively despite increase in number of clients eligible for VL. However, the median TAT remained unchanged at 29 days. There was a 60% cost savings for the program due to reduction in consumables needed for sample collection and processing and convenience in sampling among KP clients. Conclusion(s): Implementation of DBSVL resulted in increases in both VLC and VLS with an improved TAT for KPs clients in seven states of Nigeria. KPs Program implementers should consider introduction of DBSVL sampling among KPs for a better VL access and clinical outcome.
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Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).
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Background: Monash Health implemented a new telehealth-integrated antenatal care schedule in March 2020, in response to the COVID-19 pandemic. Given ever-increasing healthcare costs, new interventions must be evaluated to ensure value for money. Method(s): We conducted a retrospective comparative cost analysis from the health service and patient perspective. Women with a singleton pregnancy who received antenatal care and gave birth at Monash Health from 1 January 2018 to 22 March 2020 (pre-telehealth) and 20 April 2020 to 31 December 2021 (post-telehealth) were included. We generated propensity score matched pre- and post-telehealth cohorts, balancing baseline characteristics and comorbidities. We assigned costs for all episodes of care at Monash Health and calculated the average cost per birth in each cohort. Travel costs were estimated using the average travel distance and time. Result(s): Matched pre- and post-telehealth cohorts (both n = 13 534) were generated from the pre-telehealth ( n = 18 628) and post-telehealth ( n = 14 137) populations. We found an AU$122 increase per birth, for a total cost of AU$12 069 per birth post-telehealth. This was mainly driven by an AU$188 per birth increase in outpatient costs, associated with an extra half an appointment per birth, but offset by an AU$99 per birth decrease in patient travel costs. Differences in clinical outcomes are described in Table 1. Conclusion(s): Telehealth-integrated antenatal care enabled the health service to provide safe, ongoing care for more complex pregnancies during the pandemic for only a minimal cost increase. The results highlight the need for more research into obstetric telehealth, including more comprehensive valuations of benefits and costs to all stakeholders.
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Allogeneic hematopoietic stem cell transplantation (allo- HSCT) has traditionally involves administering fresh peripheral blood or bone marrow stem cells. At onset of the COVID-19 pandemic in March 2020, the National Marrow Donor Program (NDMP) mandated cryopreservation of all unrelated peripheral blood stem cell (PBSC) products to prevent interruptions in transplant plans by donor COVID-19 infection after recipient's start of conditioning chemotherapy. Since the lifting of this mandate, many centers have continued to cryopreserve grafts prior to initiation of conditioning, but the longer-term clinical outcomes of this practice including chronic graft versus host disease (cGVHD) rates of patients receiving cryopreserved stem cells have not been previously well described. Prior work has raised concern for a deleterious effect of cryopreservation on overall survival and non-relapse mortality (PMID: 33865804). However, heterogeneity in the patient population and reason for cryopreservation suggest that further study is needed to assess these outcomes. Here we report our single-institution experience of clinical outcomes using cryopreserved versus fresh URD PBSCs for allo-HSCT. We examined long-term outcomes in 387 patients who received unrelated donor (URD) PBSCs (136 cryopreserved, 251 fresh) between January 1, 2019 and July 31, 2021. The cohorts had similar baseline characteristics including donor/recipient age/sex, disease, conditioning regimen/intensity, and GVHD prophylaxis regimens. Two-year OS, PFS, relapse, NRM, and acute GVHD rates were not different between recipients of fresh versus cryopreserved PBSCs. Strikingly, 2-year incidence of cGVHD (28% vs 52%, p=0.00001) and moderate/severe cGVHD (9% vs 24%, p=0.00016) was substantially lower in recipients of cryopreserved PBSCs compared to fresh, respectively (Figure 1). This difference was only noted in patients receiving a GVHD prophylaxis regimen without post-transplantation cyclophosphamide (PTCY) (no PTCY 2-year cGVHD incidence cryopreserved vs fresh: 29% vs 57%, p=0.000016), moderate/severe cGVHD 16% vs 34%, p=0.0006) (Figure 2). For patients receiving a PTCY-containing GVHD prophylaxis regimen, there was no difference in cGVHD incidence (cGVHD cryopreserved vs fresh: 24% vs 27%, p=0.56, moderate/severe cGVHD 7% vs 9.3%, p=0.3, Figure 3). (Figure Presented) (Figure Presented) (Figure Presented) While survival and relapse rates are not different, cryopreservation is associated with a marked reduction in cGVHD rates in the setting of non-PTCy based GVHD prophylaxis. Larger multicenter or registry analyses are needed to confirm these observations and may prompt a re-assessment of the role of cryopreservation of stem cell products in clinical practice. If confirmed, it will be critical to understand the immunologic consequences of cryopreservation and how they might influence the clinical impact on chronic GVHDCopyright © 2023 American Society for Transplantation and Cellular Therapy
ABSTRACT
Background: Crystalloid fluid administration has traditionally played an important role in prevention of hemorrhagic cystitis with high dose cyclophosphamide. Cryopreservation of stem cells in the era of the COVID pandemic has further led to an increase in crystalloid use. Excess fluid administration over a short duration could lead to volume overload, respiratory failure and impact overall survival. Method(s): A retrospective chart review was conducted on patients receiving PtCy following Haplo SCT at UVA Medical Center from September 2016 through August 2022. Internal BMT quality audit in June 2021 identified increased rate of ICU transfers and respiratory failure amongst patient receiving PtCy due to fluid overload. Hence our PtCy hydration was reduced, with IV fluid administration decreasing from 200 mL/ hr over 62 hours to 100 mL/hr over 12 hours. Urine output parameters placed to administer Cytoxan were also removed. We present our quality improvement project demonstrating outcomes pre and post intervention. Result(s): All demographic patient and transplant-related data was collected during the period of hospitalization for Haplo SCT [Table 1]. Pre-intervention spanned 9/2016-8/2021. Our analysis identified higher than expected rates of respiratory (Table Presented) failure prompting intervention on 8/2021. Post-intervention spanned 8/2021-8/2022. Pre-intervention, 45% of patients receiving Haplo SCT developed respiratory failure (defined as a new hypoxia) in the 30 day post-transplant period. Of these, 93% had volume overload. Mechanical ventilation was required in 21%. Complication rates included ICU transfer - 30%, AKI - 39%, and renal replacement therapy - 18%. Three percent (1 pt) developed hemorrhagic cystitis requiring bladder irrigation. Median LOS was 31.0 days. Post-intervention, average IV crystalloid received was reduced by about 15L. Median diuretic use reduced by 40%. No instances of respiratory failure, mechanical ventilation, ICU transfer, AKI or renal replacement therapy occurred in this group. Median LOS was 26.5 days. There were no cases of hemorrhagic cystitis. Please refer Figure 1. (Figure Presented) (Figure Presented) Conclusion(s): This single center quality improvement initiative shows that reducing IV crystalloid administration with PtCy is associated with a reduction in respiratory failure and other adverse clinical outcomes, without observed increase in hemorrhagic cystitis. Larger multi-center studies are needed to validate this finding.Copyright © 2023 American Society for Transplantation and Cellular Therapy
ABSTRACT
Introduction: One of the common causes of COVID-19 related death is acute respiratory distress syndrome (C-ARDS). Dexamethasone is the cornerstone in the therapy of C-ARDS and reduces mortality probably by suppressing inflammatory levels in ICU patients. Its anti-inflammatory effects may be concentration-related. However, no pharmacokinetic studies of dexamethasone have been conducted in ICU patients. Therefore, we designed a population pharmacokinetic study to gain a deeper understanding of the pharmacokinetics of dexamethasone in critically ill patients in order to identify relevant covariates that can be used to personalize dosing regimens and improve clinical outcomes. Method(s): This was a retrospective pilot study at the ICU of the Erasmus Medical Center. Blood samples were collected in adults at the ICU with COVID who were treated with fixed dose intravenous dexamethasone (6 mg/day). The data were analyzed using Nonlinear Mixed Effects Modelling (NONMEM) software for population pharmacokinetic analysis and clinically relevant covariates were selected and evaluated. Result(s): A total of 51 dexamethasone samples were measured in 18 patients. A two-compartment model with first-order kinetics best fitted the data. The mean population estimates for drug clearance and inter-compartment clearance were 2.85 L/h (IIV 62.9%) and 2.11 L/h, respectively, and central and peripheral volumes of distribution were 15.4 L and 12.3 L, respectively. The covariate analysis showed a significant correlation between dexamethasone clearance and CRP. Dexamethasone clearance decreased significantly with increasing CRP in the range of 0-50 mg/L and a correlation was observed with CRP up to 100 mg/L. Conclusion(s): The dexamethasone PK parameters of ICU COVID patients were quite different from those come from healthy populations. Inflammation might play an important role in dexamethasone clearance and the dosing should be more individualized in order to achieve best therapeutic effect in ICU patients.
ABSTRACT
Background: There is an urgent need for more efficient models of differentiated anti-retroviral therapy (ART) delivery, with the World Health Organization and PEPFAR calling for evidence to guide whether 12-monthly ART prescriptions and clinic review (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) and clinical outcomes in South Africa. Method(s): We performed a retrospective cohort study using routine, deidentified data from 59 public clinics in KwaZulu-Natal. We included PLHIV aged >18 years with a recent suppressed viral load (VL), and who had been referred from their clinic into a community ART delivery programme with a standard 6-month prescription and clinic review (6M script) or a 12M script. In the community ART programme, PLHIV collected ART every two months at external pick-up points, before returning to the clinic after 6 or 12 months for a new script. We used multivariable modified Poisson regression, accounting for clinic clustering, to compare 12-month retention-in-care (not >90 days late for any visit) and viral suppression (< 50 copies/mL) between 6M and 12M script groups. Result(s): Among 27,148 PLHIV referred for community ART between Jun-Dec 2020, 42.6% received 6M scripts and 57.4% 12M scripts. The median age was 39 years (interquartile range [IQR] 33-46) and 69.4% were women. Age, gender, prior community ART use and time on ART were similar in the two groups (Table). However, a larger proportion of the 12M script group had a dolutegravirbased regimen (60.0% versus 46.3%). The median (IQR) number of clinic visits in the 12 months of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention at 12 months was 94.6% (95% confidence interval [CI] 94.2%- 94.9%) among those receiving 12M scripts and 91.8% (95% CI 91.3%-92.3%) among those with 6M scripts. 16.8% and 16.7% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 90.4% (95% CI 89.9%-91.0%) in the 12M group and 88.9% (95% CI 88.3%- 89.5%) in the 6M group were suppressed. After adjusting for age, gender, ART regimen, time on ART and prior community ART use, retention (adjusted risk ratio [aRR]: 1.03, 95% CI 1.01-1.04) and suppression (aRR: 1.02(1.01-1.03) were higher with 12M scripts. Conclusion(s): COVID-19 led to temporary introduction of 12M scripts in South Africa. Wider use could reduce clinic visits without negative impacts on shortterm clinical outcomes.
ABSTRACT
Introduction: The aim of this study was to determine whether there is an association between extravascular lung water index (EVLWi) and physiological respiratory dead space (VDphys/VT) and to determine if these factors are associated with the possibility to being discharged alive on day 28. Method(s): We analyzed a prospective cohort of patients with COVID ARDS supported with invasive mechanical ventilation (IMV) admitted in our ICU who were monitored with volumetric capnography and transpulmonary thermodilution (TPTD). First day TDTP and VDphys/VT were considered. Bohr-Enghoff formula was used to obtain VDphys/ VT. This protocol was approved by the local IRB and informed consent was waived. Result(s): 31 patients with matched TPTD and VDphys/VT during the first 24 h were analyzed in who EVLWi correlated with VDphys/VT (r = 0.599 p = 0.002), however, EVLWi did not associated with PaFi. Patients with EVLWi > 10 ml/kg had higher APACHE II and VDphys/VT. These patients had a lower cumulative incidence to be discharged alive on day 28 with aHR 7.3 [1.4-39.1] p = 0.02 (adjusted by APACHE II and VDphys/VT, Fig. 1A). Remarkably, patients with EVLWi > 10 ml/ kg + VDphys/VT > 57% had worse outcome compared to those who had EVLWi > 10 ml/kg + VDphys/VT < 57% (25% vs 75%, p = 0.032, Fig. 1B). Conclusion(s): In patients with COVID ARDS supported with IMV, VDphys/VT give prognostic data additional to EVLWi.