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1.
Rhode Island Medicine ; 105(7):49-54, 2022.
Article in English | MEDLINE | ID: covidwho-2011739

ABSTRACT

BACKGROUND: We hypothesized that implementation of new ultra-restrictive transfusion protocol in adult surgical intensive care units (SICU) was safe and feasible during pandemic-associated shortage crises. METHODS: Retrospective analysis two months pre- and post-implementation of ultra-restrictive transfusion protocol in March 2020 with hemoglobin cutoff of 6 g/dL (6.5 g/dL if >= 65 years old) for patients without COVID, active bleeding, or myocardial ischemia. RESULTS: We identified 16/93 and 27/168 patients PRE and POST meeting standard transfusion threshold (7 g/dL);within POST, 12 patients met ultra-restrictive cutoffs. There was no significant difference between PRE and POST in the rate of mortality, ischemic complications, or the number of transfusions per patient, however, the overall incidence of transfusion was lower in the POST group (7.1 vs 17.2%, p = 0.02). Patients received a mean (SD) of 4(3.8) and 2.4(1.5) PRBC transfusions pre- and post-implementation. Odds ratio of mortality in POST group was 0.62 (95%CI: 0.08-5.12) adjusted for age, sex, and SOFA score. CONCLUSIONS: Implementation of an ultra-restrictive transfusion protocol was feasible and effective as a blood- preservation strategy.

2.
TH Open ; 6(3):E194-E212, 2022.
Article in English | EMBASE | ID: covidwho-1956435

ABSTRACT

Thrombomodulin (TM) is a type-I transmembrane protein that is mainly expressed on endothelial cells and plays important roles in many biological processes. Circulating TM of different forms are also present in biofluids, such as blood and urine. Soluble TM (sTM), comprised of several domains of TM, is the major circulating TM which is generated by either enzymatic or chemical cleavage of the intact protein under different conditions. Under normal conditions, sTM is present in low concentrations (<10 ng/mL) in the blood but is elevated in several pathological conditions associated with endothelial dysfunction such as cardiovascular, inflammatory, infection, and metabolic diseases. Therefore, sTM level has been examined for monitoring disease development, such as disseminated intravascular coagulation (DIC), sepsis and multiple organ dysfunction syndrome in patients with novel coronavirus disease 2019 (COVID-19) recently. In addition, microvesicles (MVs) that contain membrane TM (MV-TM) have been found to be released from activated cells which also contribute to levels of circulating TM in certain diseases. Several release mechanisms of sTM and MV-TM have been reported, including enzymatic, chemical, and TM mutation mechanisms. Measurements of sTM and MV-TM have been developed and explored as biomarkers in many diseases. In this review, we summarize all these advances in three categories as follows: (1) release mechanisms of circulating TM, (2) methods for measuring circulating TM in biological samples, and (3) correlation of circulating TM with diseases. Altogether, it provides a whole picture of recent advances on circulating TM in health and disease.

3.
mBio ; : e0145422, 2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-1950003

ABSTRACT

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.

4.
Scand J Public Health ; 50(6): 686-692, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1923464

ABSTRACT

AIMS: The Danish authorities implemented a differential rollout of the COVID-19 vaccines where individuals at high risk of COVID-19 were prioritized. We describe the temporal uptake and characteristics of COVID-19 vaccine recipients in Denmark. METHODS: Using nationwide healthcare registries, we identified all Danish residents ⩾5 years of age who received at least one dose of a COVID-19 vaccine from 27 December 2020-29 January 2022. We charted the daily number of newly vaccinated individuals and the cumulative vaccine coverage over time, stratified by vaccine type, age groups and vaccination priority groups, and described characteristics of vaccine recipients during two-month-intervals and in vaccination priority groups. RESULTS: By 29 January 2022, 88%, 86% and 64% of Danish residents ⩾5 years (n=5,562,008) had received a first, second and third dose, respectively, of a COVID-19 vaccine, most commonly the BNT162b2 vaccine (84%). Uptake ranged from 48% in 5-11-year-olds to 98% in 65-74-year-olds. Individuals vaccinated before June 2021 were older (median age 61-70 years vs 10-35 years in later periods) and had more comorbidities such as hypertension (22-28% vs 0.77-2.8% in later periods), chronic lung disease (9.4-15% vs 3.7-4.6% in later periods) and diabetes (9.3-12% vs 0.91-2.4% in later periods). CONCLUSIONS: We document substantial changes over time in, for example, age, sex and medical history of COVID-19 vaccine recipients. Though these results are related to the differential vaccine rollout in Denmark, similar findings are probable in other countries and should be considered when designing and interpreting studies on the effectiveness and safety of COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , Denmark/epidemiology , Humans , Middle Aged , Vaccination
5.
Clinical and Experimental Rheumatology ; 40(5):S3-S11, 2022.
Article in English | English Web of Science | ID: covidwho-1880929

ABSTRACT

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

7.
JAMA Pediatr ; 176(3): 236-243, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1864299

ABSTRACT

IMPORTANCE: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. OBJECTIVE: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. RESULTS: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). CONCLUSIONS AND RELEVANCE: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39.


Subject(s)
Nephrotic Syndrome , Respiratory Tract Infections , Adrenal Cortex Hormones/therapeutic use , Child , Humans , Male , Nephrotic Syndrome/complications , Nephrotic Syndrome/drug therapy , Prednisolone/therapeutic use , Quality of Life , Recurrence , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/prevention & control
8.
S Afr Med J ; 112(4): 279-287, 2022 04 04.
Article in English | MEDLINE | ID: covidwho-1857301

ABSTRACT

BACKGROUND: Major causes of under-5 child deaths in South Africa (SA) are well recognised, and child mortality rates are falling. The focus of child health is therefore shifting from survival to disease prevention and thriving, but local data on the non-fatal disease burden are limited. Furthermore, COVID-19 has affected children's health and wellbeing, both directly and indirectly. OBJECTIVES: To describe the pattern of disease on admission of children at different levels of care, and assess whether this has been affected by COVID-19. METHODS: Retrospective reviews of children's admission and discharge registers were conducted for all general hospitals in iLembe and uMgungundlovu districts in KwaZulu-Natal Province, SA, from January 2018 to September 2020. The Global Burden of Disease framework was adapted to create a data capture sheet with four broad diagnostic categories and 37 specific cause categories. Monthly admission numbers were recorded per cause category, and basic descriptive analysis was completed in Microsoft Excel. RESULTS: Overall, 36 288 admissions were recorded across 18 hospital wards, 32.0% at district, 49.8% at regional and 18.2% at tertiary level. Communicable diseases, perinatal conditions and nutritional deficiencies (CPNs) accounted for 37.4% of admissions, non-communicable diseases (NCDs) for 43.5% and injuries for 17.1%. The distribution of broad diagnostic categories varied across levels of care, with CPNs being more common at district level and NCDs more common at regional and tertiary levels. Unintentional injuries represented the most common cause category (16.6%), ahead of lower respiratory tract infections (16.1%), neurological conditions (13.6%) and diarrhoeal disease (8.4%). The start of the local COVID-19 outbreak coincided with a 43.1% decline in the mean number of monthly admissions. Admissions due to neonatal conditions and intentional injuries remained constant during the COVID-19 outbreak, while those due to other disease groups (particularly respiratory infections) declined. CONCLUSIONS: Our study confirms previous concerns around a high burden of childhood injuries in our context. Continued efforts are needed to prevent and treat traditional neonatal and childhood illnesses. Concurrently, the management of NCDs should be prioritised, and evidence-based strategies are sorely needed to address the high injury burden in SA.


Subject(s)
COVID-19 , Noncommunicable Diseases , COVID-19/epidemiology , Child , Disease Outbreaks , Female , Hospitals , Humans , Infant, Newborn , Noncommunicable Diseases/epidemiology , Pregnancy , Retrospective Studies , South Africa/epidemiology
9.
Preprint in English | bioRxiv | ID: ppbiorxiv-494461

ABSTRACT

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to SARS-CoV disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse Chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6 that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2 and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species.

10.
J R Soc Med ; : 1410768221089016, 2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1820009

ABSTRACT

OBJECTIVES: During the worldwide COVID-19 pandemic, elective cardiac surgery was suspended to provide ICU beds for COVID-19 patients and those requiring urgent cardiac surgery. The aim of this study is to assess the effect of the pandemic on outcomes of patients awaiting elective cardiac surgery. DESIGN: A multi-centre prospective cohort study. SETTING: The elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres. PARTICIPANTS: Patients on the elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres. MAIN OUTCOME MEASURES: Primary outcome was surgery, percutaneous therapy or death at one year. METHODS: Data were collected prospectively on patients on the elective adult cardiac surgery waiting list as of 1 March 2020 across seven UK cardiac surgical centres. Primary outcome was surgery, percutaneous therapy or death at one year. Demographic data and outcomes were obtained from local electronic records, anonymised and submitted securely to the lead centre for analysis. RESULTS: On 1 March 2020, there were 1099 patients on the elective waiting list for cardiac surgery. On 1 March 2021, 83% (n = 916) had met a primary outcome. Of these, 840 (92%) had surgery after a median of 195 (118-262) days on waiting list, 34 (3%) declined an offer of surgery, 23 (3%) had percutaneous intervention, 12 (1%) died, 7 (0.6%) were removed from the waiting list. The remainder of patients, 183 (17%) remained on the elective waiting list. CONCLUSIONS: This study has shown, for the first time, significant delays to treatment of patients awaiting elective cardiac surgery. Although there was a low risk of mortality or urgent intervention, important unmeasured adverse outcomes such as quality of life or increased perioperative risk may be associated with prolonged waiting times.

11.
J Crit Care ; 70: 154045, 2022 08.
Article in English | MEDLINE | ID: covidwho-1814672

ABSTRACT

PURPOSE: Prolonged observation could avoid invasive mechanical ventilation (IMV) and related risks in patients with Covid-19 acute respiratory failure (ARF) compared to initiating early IMV. We aimed to determine the association between ARF management strategy and in-hospital mortality. MATERIALS AND METHODS: Patients in the Weill Cornell Covid-19 registry who developed ARF between March 5 - March 25, 2020 were exposed to an early IMV strategy; between March 26 - April 1, 2020 to an intermediate strategy; and after April 2 to prolonged observation. Cox proportional hazards regression was used to model in-hospital mortality and test an interaction between ARF management strategy and modified sequential organ failure assessment (mSOFA). RESULTS: Among 632 patients with ARF, 24% of patients in the early IMV strategy died versus 28% in prolonged observation. At lower mSOFA, prolonged observation was associated with lower mortality compared to early IMV (at mSOFA = 0, HR 0.16 [95% CI 0.04-0.57]). Mortality risk increased in the prolonged observation strategy group with each point increase in mSOFA score (HR 1.29 [95% CI 1.10-1.51], p = 0.002). CONCLUSION: In Covid-19 ARF, prolonged observation was associated with a mortality benefit at lower mSOFA scores, and increased mortality at higher mSOFA scores compared to early IMV.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Respiratory Insufficiency , COVID-19/therapy , Hospital Mortality , Humans , Organ Dysfunction Scores , Respiration, Artificial , Respiratory Insufficiency/therapy
12.
South African Medical Journal ; 112(4):279-287, 2022.
Article in English | EMBASE | ID: covidwho-1798764

ABSTRACT

Background. Major causes of under-5 child deaths in South Africa (SA) are well recognised, and child mortality rates are falling. The focus of child health is therefore shifting from survival to disease prevention and thriving, but local data on the non-fatal disease burden are limited. Furthermore, COVID-19 has affected children's health and wellbeing, both directly and indirectly. Objectives. To describe the pattern of disease on admission of children at different levels of care, and assess whether this has been affected by COVID-19. Methods. Retrospective reviews of children's admission and discharge registers were conducted for all general hospitals in iLembe and uMgungundlovu districts in KwaZulu-Natal Province, SA, from January 2018 to September 2020. The Global Burden of Disease framework was adapted to create a data capture sheet with four broad diagnostic categories and 37 specific cause categories. Monthly admission numbers were recorded per cause category, and basic descriptive analysis was completed in Microsoft Excel. Results. Overall, 36 288 admissions were recorded across 18 hospital wards, 32.0% at district, 49.8% at regional and 18.2% at tertiary level. Communicable diseases, perinatal conditions and nutritional deficiencies (CPNs) accounted for 37.4% of admissions, non-communicable diseases (NCDs) for 43.5% and injuries for 17.1%. The distribution of broad diagnostic categories varied across levels of care, with CPNs being more common at district level and NCDs more common at regional and tertiary levels. Unintentional injuries represented the most common cause category (16.6%), ahead of lower respiratory tract infections (16.1%), neurological conditions (13.6%) and diarrhoeal disease (8.4%). The start of the local COVID-19 outbreak coincided with a 43.1% decline in the mean number of monthly admissions. Admissions due to neonatal conditions and intentional injuries remained constant during the COVID-19 outbreak, while those due to other disease groups (particularly respiratory infections) declined. Conclusions. Our study confirms previous concerns around a high burden of childhood injuries in our context. Continued efforts are needed to prevent and treat traditional neonatal and childhood illnesses. Concurrently, the management of NCDs should be prioritised, and evidence-based strategies are sorely needed to address the high injury burden in SA.

13.
PLoS One ; 17(2): e0263995, 2022.
Article in English | MEDLINE | ID: covidwho-1686111

ABSTRACT

Older individuals with chronic health conditions are at highest risk of adverse clinical outcomes from COVID-19, but there is widespread belief that risk to younger, relatively lower-risk individuals is negligible. We assessed the rate and predictors of life-threatening complications among relatively lower-risk adults hospitalized with COVID-19. Of 3766 adults hospitalized with COVID-19 to three hospitals in New York City from March to May 2020, 963 were relatively lower-risk based on absence of preexisting health conditions. Multivariable logistic regression models examined in-hospital development of life-threatening complications (major medical events, intubation, or death). Covariates included age, sex, race/ethnicity, hypertension, weight, insurance type, and area-level sociodemographic factors (poverty, crowdedness, and limited English proficiency). In individuals ≥55 years old (n = 522), 33.3% experienced a life-threatening complication, 17.4% were intubated, and 22.6% died. Among those <55 years (n = 441), 15.0% experienced a life-threatening complication, 11.1% were intubated, and 5.9% died. In multivariable analyses among those ≥55 years, age (OR 1.03 [95%CI 1.01-1.06]), male sex (OR 1.72 [95%CI 1.14-2.64]), being publicly insured (versus commercial insurance: Medicare, OR 2.02 [95%CI 1.22-3.38], Medicaid, OR 1.87 [95%CI 1.10-3.20]) and living in areas with relatively high limited English proficiency (highest versus lowest quartile: OR 3.50 [95%CI 1.74-7.13]) predicted life-threatening complications. In those <55 years, no sociodemographic factors significantly predicted life-threatening complications. A substantial proportion of relatively lower-risk patients hospitalized with COVID-19 experienced life-threatening complications and more than 1 in 20 died. Public messaging needs to effectively convey that relatively lower-risk individuals are still at risk of serious complications.


Subject(s)
COVID-19/pathology , Hospitalization/statistics & numerical data , Hypertension/complications , Age Factors , COVID-19/complications , COVID-19/ethnology , COVID-19/virology , Female , Hospital Mortality , Humans , Length of Stay , Logistic Models , Male , Middle Aged , New York City , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Sex Factors
14.
J Exp Med ; 219(2)2022 02 07.
Article in English | MEDLINE | ID: covidwho-1593236

ABSTRACT

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.


Subject(s)
Disease Models, Animal , Disease Susceptibility , Virus Diseases/etiology , Virus Diseases/transmission , Animal Diseases/transmission , Animal Diseases/virology , Animals , Biomarkers , Host-Pathogen Interactions , Humans , Interferons/metabolism , Mice , Mice, Knockout , Microbial Interactions , Rodentia , Virus Diseases/metabolism
15.
Gastroenterology ; 160(6):S-189-S-190, 2021.
Article in English | EMBASE | ID: covidwho-1591389

ABSTRACT

Background: COVID-19 patients are at increased risk of venous thromboembolism (VTE) requiring the use of anticoagulation. Gastrointestinal bleeding (GIB) is increasingly being reported, complicating the decision to initiate or resume anticoagulation as providers balance the risk of thrombotic disease with the risk of bleeding. Aim: Our primary aim is to assess rebleeding rates in COVID-19 patients with GIB and determine whether endoscopic evaluation and anticoagulation use affects these rates. Our secondary aim is to determine the 30-day VTE and mortality rates in this cohort. Methods: This is a retrospective study that reviewed 56 cases of COVID-19 patients with GIB admitted to the hospital between March 4th – May 25th. All patients tested positive for COVID 19 with reverse transcriptase polymerase chain reaction nasopharyngeal swabs. The cases were reviewed for the following outcomes: rates of therapeutic intervention, 30-day rebleeding, 30-day VTE events and 30-day mortality. Results: 23/56 (41%) of COVID-19 patients with GIB rebled within 30 days. There was no reduction in rebleeding rate with endoscopic therapy compared to medical management alone (39% vs. 42%, p=0.81). There was no difference in 30 day rebleeding rate among patients restarted on anticoagulation after endoscopy compared to those that were restarted on anticoagulation after medical management alone (41% vs 29%, p = 0.47). 15/56 (27%) of the cohort had VTE during their hospitalization, 53% of which were diagnosed after anticoagulation was held due to GIB. Patients that undergone endoscopy were more likely to be initiated or resumed on anticoagulation after bleed then those that did not (87% vs 55%, p=0.02). The all-cause 30-day mortality and GI-bleeding related deaths were 32% and 9% respectively. There was no difference in 30 day mortality rate among patients that were restarted on anticoagulation after endoscopic management compared to those restarted on anticoagulation after conservative management alone (24% vs 29%, p=0.70). Conclusions: In this cohort, while there was no difference in rebleeding rate when comparing endoscopic therapy to conservative management, patients who underwent endoscopy were more likely to be restarted on anticoagulation. Given that there was no difference in rebleeding or mortality rates among those restarted on anticoagulation after endoscopy compared to patients that were restarted on anticoagulation after conservative management, it seems reasonable to re-challenge COVID-19 patients who have stopped bleeding with anticoagulation even if endoscopy cannot be performed. However, larger studies are needed to guide management of these complex patients.(Table Presented) (Table Presented)

16.
Blood ; 138:4023, 2021.
Article in English | EMBASE | ID: covidwho-1582390

ABSTRACT

BACKGROUND: Autologous stem cell transplantation (ASCT) for multiple myeloma (MM) entails sudden life changes including acute symptom burden, changes in physical function, and shifting caregiver dynamics. Several studies have shown that anxiety, insomnia, and distress rise in the initial weeks following ASCT before slowly recovering. Long-term consequences of these acute exacerbations include persistent quality of life (QOL) impairments (El-Jawahri 2016), post-traumatic stress disorder (Griffith 2020), and the usage of potentially inappropriate medications (PIMs) for symptom management (Banerjee 2021). We have recently completed a pilot study of digital life coaching (DLC), whereby life coaches work with patients via phone calls and text messages to provide longitudinal support, education, and accountability to meet wellbeing-related goals. Our pilot study of 15 patients demonstrated the feasibility of DLC during this period, with bidirectional patient-coach engagement occurring every 5-7 days even during index hospitalizations for ASCT (Banerjee 2021). Based on these positive results, we have now launched a randomized Phase 2 study of DLC versus usual care among patients with MM undergoing ASCT. STUDY DESIGN: Our study is registered at clinicaltrials.gov as NCT04589286. We plan to enroll 60 adult patients with MM undergoing first ASCT at our institution. Inclusion criteria include English language proficiency and ownership of a personal cellphone. However, neither smartphones nor specific mobile apps are required for study participation. All patients, including those in the control arm, receive brief wellness-related tips with each request for PRO data as outlined below. As shown in the Figure, patients in the DLC arm are paired with a trained life coach beginning at Day -10 before ASCT. Coaches use structured frameworks to assist patients longitudinally with identifying and accomplishing wellbeing-related goals. Specific coaching topics can vary from week to week and are set by each patient. In addition to weekly coach-led phone calls, patients are encouraged to maintain bidirectional communication via phone/text/email as often as desired. Patients in the control arm do not receive access to DLC. Our primary endpoint is the total usage of sedative-class PIMs - including lorazepam, temazepam, zolpidem, and other similar medications - prescribed for anxiety or insomnia during each of 4 four-week study subperiods identified in the Figure. Secondary endpoints include patient-reported outcome (PRO) assessments of QOL (PROMIS Global Health), distress (NCCN Distress Thermometer), and insomnia (PROMIS Sleep Disturbances 4A). PRO assessments are collected exclusively using automated REDCap emails every 1-2 weeks as shown in the Figure. PROGRESS TO DATE: As of the data cutoff (7/31/21), 19 patients have enrolled onto our study and 5 have completed all follow-up. The median age of enrolled patients is 62 (range: 31-77), with 26% of patients aged 70 or older. As shown in our pilot study (Banerjee 2021), PRO collection via automated REDCap emails is feasible. Specifically, of 93 email-based requests for PRO assessments as of the data cutoff, 92 (99%) have been completed. Analyses of PRO assessment responses and PIM usage will be conducted after study completion. DISCUSSION: Improving patient wellbeing during the acute peri-ASCT period is an unmet need in multiple myeloma. Published supportive strategies during this time include music therapy (Bates 2017), acupuncture (Deng 2018), palliative care (El-Jawahri 2017), and programmed hospital room lighting (Valdimarsdottir 2018). DLC may offer unique advantages given its easy accessibility and unified patient-facing interface across hospital/clinic/home transitions. These strengths may be particularly relevant in light of the COVID-19 pandemic, where home-based follow-up after ASCT has become more common. That being said, broadening the accessibility of DLC to include patients with limited English proficiency or patients without personal cell phones are important priorities for fu ure studies. In summary, our randomized Phase 2 study of DLC versus usual care is ongoing. If shown to reduce PIM prescription rates while improving wellbeing-related PRO trajectories longitudinally, DLC may become a standard of care for patients with hematologic malignancies undergoing ASCT. [Formula presented] Disclosures: Banerjee: Pack Health: Research Funding;SparkCures: Consultancy;Sanofi: Consultancy. Knoche: Amgen: Honoraria. Brassil: Abbvie: Research Funding;Astellas: Research Funding;BMS: Research Funding;Daiichi Sankyo: Research Funding;Genentech: Research Funding;GSK: Research Funding;Sanofi: Research Funding;Pack Health: Current Employment. Jackson: Pack Health: Current Employment. Patel: Pack Health: Current Employment. Lo: Oncopeptides: Consultancy;EUSA Pharma: Consultancy. Chung: Caelum: Research Funding. Wong: Amgen: Consultancy;Genentech: Research Funding;Fortis: Research Funding;Janssen: Research Funding;GloxoSmithKlein: Research Funding;Dren Biosciences: Consultancy;Caelum: Research Funding;BMS: Research Funding;Sanofi: Membership on an entity's Board of Directors or advisory committees. Wolf: Adaptive Biotechnologies: Consultancy;Teneobio: Consultancy;Sanofi: Consultancy;Amgen: Consultancy. Martin: Oncopeptides: Consultancy;Sanofi: Research Funding;Amgen: Research Funding;Janssen: Research Funding;GlaxoSmithKline: Consultancy. Shah: Bluebird Bio: Research Funding;GSK: Consultancy;Janssen: Research Funding;Indapta Therapeutics: Consultancy;BMS/Celgene: Research Funding;CareDx: Consultancy;CSL Behring: Consultancy;Kite: Consultancy;Nektar: Research Funding;Karyopharm: Consultancy;Amgen: Consultancy;Oncopeptides: Consultancy;Poseida: Research Funding;Precision Biosciences: Research Funding;Sanofi: Consultancy;Sutro Biopharma: Research Funding;Teneobio: Research Funding.

17.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):515-516, 2021.
Article in English | EMBASE | ID: covidwho-1570425

ABSTRACT

Background: In our setting,it is common for patients to be “labelled” as allergic in the presence of doubtful clinical signs of intolerance or allergic reaction. Moreover,it is not uncommon that patients who have been ruled out allergy to beta-lactam antibiotics (BL-ATB) continue to be mislabelled allergologically in the electronic medical records.Unfortunately,this mistake means that they are sometimes deprived of the first therapeutic option. Objective: The main objective of the study was to assess the correct labelling of patients(p) from an allergological point of view in Primary Care,in the Emergency Department and in visits to other specialists. The secondary objectives were:to determine the percentage of patients who received BL-ATB, the reason for the prescription and the drugs used. Method: Prospective review of the medical records of 92 patients who have been ruled out allergy to BL-ATB in our department during the months of August 1st,2019, to March 31st,2020.All patients have been followed for at least 12 months.Data were collected by reviewing the electronic medical records. Results: Of the 92 patients, only 64%(54p) were well identified in primary care. Only 36%(33p) had attended the Emergency Department,of which 76%(25p) were correctly identified and the remaining 24%(8p) were not. 38%(35p) were visited by an specialist, in a total of 42 visits(v). In 74% of the visits (31v) the patients were correctly identified and in the remaining 26% they were not.Table 1 summarises the number of visits to each specialist and the correct or incorrect allergological identification. Only 17%(16p) received BL-ATB, on a total of 20 occasions.Urinary tract infections were the most frequent reason for prescribing BL-ATB (4p), followed by H.Pilory infection(3p),skin infections(3p),respiratory infections(3p),sepsis (2p),acute otitis media(1p),pharyngitis(1p),sinusit is(1p),oral infections(1p) and bone fractures(1p). Amoxicillin was the most commonly used drug(8p),followed by Amoxicillin/Clavulanic acid(5p),Cefuroxime(2p),Meropenem(2p),Cef triaxone (1p) and Piperacillin/Tazobactam(1p). Conclusion: Despite the efforts being made by Allergology services to correctly label patients with HS to BL, a high percentage remain misidentified. In relation to the consumption of BL-ATB, we believe that the data are underestimated,given that during the months of follow-up of the study (year 2020) the use of masks and hand washing recommended by the COVID-19 pandemic have reduced both infections and access to health care. (Table Presented).

18.
PLoS One ; 16(11): e0257979, 2021.
Article in English | MEDLINE | ID: covidwho-1526683

ABSTRACT

Public health interventions such as social distancing and mask wearing decrease the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they decrease the viral load of infected patients and whether changes in viral load impact mortality from coronavirus disease 2019 (COVID-19). We evaluated 6923 patients with COVID-19 at six New York City hospitals from March 15-May 14, 2020, corresponding with the implementation of public health interventions in March. We assessed changes in cycle threshold (CT) values from reverse transcription-polymerase chain reaction tests and in-hospital mortality and modeled the impact of viral load on mortality. Mean CT values increased between March and May, with the proportion of patients with high viral load decreasing from 47.7% to 7.8%. In-hospital mortality increased from 14.9% in March to 28.4% in early April, and then decreased to 8.7% by May. Patients with high viral loads had increased mortality compared to those with low viral loads (adjusted odds ratio 2.34). If viral load had not declined, an estimated 69 additional deaths would have occurred (5.8% higher mortality). SARS-CoV-2 viral load steadily declined among hospitalized patients in the setting of public health interventions, and this correlated with decreases in mortality.


Subject(s)
COVID-19/virology , Hospital Mortality/trends , Viral Load/statistics & numerical data , COVID-19/epidemiology , COVID-19/mortality , COVID-19 Nucleic Acid Testing/statistics & numerical data , Female , Humans , Male , New York , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
19.
Hepatology ; 74(SUPPL 1):554A, 2021.
Article in English | EMBASE | ID: covidwho-1508767

ABSTRACT

Background: Despite new U.S. Centers for Disease Control and U.S. Preventative Services Taskforce guidelines for universal screening of all adults aged 18 and older for hepatitis C virus (HCV), many remain undiagnosed, and even more so due to the COVID-19 pandemic. Machine learning (ML) algorithms are potentially effective at improving the HCV care cascade. We evaluate the potential cost-effectiveness of a ML algorithm to identify undiagnosed HCV patients in care, using data from an algorithm developed based on U.S. ambulatory electronic medical records (EMR). Methods: The algorithm was trained using 16M patients from U.S. ambulatory EMR data across primary and specialty care from 2015-2020. The algorithm was developed to identify undiagnosed HCV patients in a 12-month prediction window using medical history from a 24-month lookback with a 1-month offset. Algorithmic sensitivity for various levels of Positive Predictive Value (PPV) was assessed on an independent cross section of the data. A HCV natural history Markov model was used to evaluate the cost-effectiveness of the ML algorithm compared to status quo screening used to identify patients over the training data period (risk-based and birth-cohort screening, PPV ~2%). We compared the status quo to scenarios with the machine learning algorithm at different sensitivity levels (5-100%). We identified optimal algorithm sensitivity which maximized health (measured in quality-adjusted life years, QALYs) while staying under a willingness-to-pay threshold of USD$100,000/QALY gained. Based on the algorithm's performance on EMR data, we assumed patients were diagnosed 6.5 months sooner than status quo. Results: The ML algorithm was cost-effective (ICER<$100k/QALY gained) in identifying undiagnosed HCV patients for sensitivity levels of up to 40% (Figure 1). The optimal sensitivity level of 40% (PPV 0.17%) resulted in incremental costs of $96.90 [95% CI 77-118] and incremental QALYs of 0.0011 [95% CI 0.0008-0.0014], and produced a mean ICER of $92,245/QALY gained. Conclusion: ML algorithms to identify undiagnosed HCV patients could be cost-effective in the U.S., so evaluating real-world effectiveness is warranted. As algorithms can be tuned to a desired tradeoff between PPV and sensitivity, economic modeling can inform this tradeoff.

20.
Multiple Sclerosis Journal ; 27(2 SUPPL):233, 2021.
Article in English | EMBASE | ID: covidwho-1496027

ABSTRACT

Background and Aims: The SARS-CoV-2 pandemic supposed a challenge in the management of patients with multiple sclerosis (MS), many of them with disease-modifying therapy (DMT)that may compromise their immune system. The aim of this study is to analyse the impact of the pandemic on the MS patient cohort of our centre in terms of incidence and severity of COVID and impact on MS. Methods: Retrospective descriptive study of MS patients with SARS-CoV-2 infection. We analysed demographic, clinical, laboratory and treatment variables. Results: Of 543 patients diagnosed with MS, 51 patients were affected by SARS-CoV-2 (9.3%). The baseline characteristics of this sample were: 66.7 % female, median age 44 years (range 18-71), 71 % relapsing-remitting MS, 13.7 % secondary progressive MS and 15.7 % primary progressive MS. The median baseline EDSS was 1.5 (interquartile range 0.75-6). 88.2 % were on DMT;62.7 % on long-term (> 24 months on same DMT). Treatment attitude was: 66.6 % no change, 27.3 % dose delay, 3 % transient discontinuation, 3 % change. Patients with MS and COVID presented with multiple symptoms, notably fever(62.7%), cough and asthenia(41.2%), dyspnoea( 19.6%), anosmia(11.8%) and headache(7.8%). 12% were asymptomatic. Bilateral pneumonia occurred in 28%, 13.7% required hospital admission. No patient died. There were 2 patients(4%) with a relapse. However, 18% had a worsening in EDSS score. EMPP subtype was associated with worsening in this period. In multivariate analysis there were no variables associated with worse outcome regarding the infection and MS. Conclusions: There were a low proportion of MS patients who suffered COVID19. Although there were some patients with severe presentation (pneumonia), there were no deaths. A significant proportion of MS patients with COVID worsen their disability status measured by EDSS, independent of relapses. Probably due to decreased physical activity due to confinement, but more studies are needed to confirm this hypothesis.

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