scholarly journals Combinatorial analysis of phenotypic and clinical risk factors associated with hospitalized COVID-19 patients

Author(s):  
Sayoni Das ◽  
Matthew Pearson ◽  
Krystyna Taylor ◽  
Veronique Bouchet ◽  
Gert Lykke Møller ◽  
...  

1AbstractCharacterization of the risk factors associated with variability in the clinical outcomes of COVID-19 is important. Our previous study using genomic data identified a potential role of calcium and lipid homeostasis in severe COVID-19. This study aimed to identify similar combinations of features (disease signatures) associated with severe disease in a separate patient population with purely clinical and phenotypic data.The PrecisionLife combinatorial analytics platform was used to analyze features derived from de-identified health records in the UnitedHealth Group COVID-19 Data Suite. The platform identified and analyzed 836 disease signatures in two cohorts associated with increased risk of COVID-19 hospitalization. Cohort 1 was formed of cases hospitalized with COVID-19 and a set of controls who developed mild symptoms. Cohort 2 included Cohort 1 individuals for whom additional laboratory test data was available.We found several disease signatures where lower levels of lipids were found co-occurring with lower levels of serum calcium and leukocytes. Many of the low lipid signatures were independent of statin use and 50% of cases with hypocalcemia signatures were reported with vitamin D deficiency. These signatures may be attributed to similar mechanisms linking calcium and lipid signaling where changes in cellular lipid levels during inflammation and infection affect calcium signaling in host cells.This study and our previous genomics analysis demonstrate that combinatorial analysis can identify disease signatures associated with the risk of developing severe COVID-19 separately from genomic or clinical data in different populations. Both studies suggest associations between calcium and lipid signalling in severe COVID-19.

2021 ◽  
Vol 3 ◽  
Author(s):  
Sayoni Das ◽  
Matthew Pearson ◽  
Krystyna Taylor ◽  
Veronique Bouchet ◽  
Gert Lykke Møller ◽  
...  

Characterization of the risk factors associated with variability in the clinical outcomes of COVID-19 is important. Our previous study using genomic data identified a potential role of calcium and lipid homeostasis in severe COVID-19. This study aimed to identify similar combinations of features (disease signatures) associated with severe disease in a separate patient population with purely clinical and phenotypic data. The PrecisionLife combinatorial analytics platform was used to analyze features derived from de-identified health records in the UnitedHealth Group COVID-19 Data Suite. The platform identified and analyzed 836 disease signatures in two cohorts associated with an increased risk of COVID-19 hospitalization. Cohort 1 was formed of cases hospitalized with COVID-19 and a set of controls who developed mild symptoms. Cohort 2 included Cohort 1 individuals for whom additional laboratory test data was available. We found several disease signatures where lower levels of lipids were found co-occurring with lower levels of serum calcium and leukocytes. Many of the low lipid signatures were independent of statin use and 50% of cases with hypocalcemia signatures were reported with vitamin D deficiency. These signatures may be attributed to similar mechanisms linking calcium and lipid signaling where changes in cellular lipid levels during inflammation and infection affect calcium signaling in host cells. This study and our previous genomics analysis demonstrate that combinatorial analysis can identify disease signatures associated with the risk of developing severe COVID-19 separately from genomic or clinical data in different populations. Both studies suggest associations between calcium and lipid signaling in severe COVID-19.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S576-S577
Author(s):  
Thomas Holowka ◽  
Harry Cheung ◽  
Maricar F Malinis ◽  
Sarah Perreault ◽  
Iris Isufi ◽  
...  

Abstract Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p < 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p < 0.001), neutropenia (OR 3.6, p < 0.01), lymphopenia (OR 2.4, p < 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p < 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 77-78
Author(s):  
S. Do ◽  
J. H. Du ◽  
J. X. An ◽  
J. Wang ◽  
A. Lin

Background:Hydroxychloroquine (HCQ) is commonly used for the treatment of various autoimmune diseases. The medication is generally well-tolerated. However, long-term use after 5 years may increase the risk of retinopathy. One study in 2014 has demonstrated the risk can be as high as 7.5%. Optical Coherence Tomography (OCT) has become a major modality in screening retinopathy.Objectives:To evaluate the prevalence of retinal toxicity among patients using hydroxychloroquine and to determine various risk factors associated with hydroxychloroquine-associated retinal toxicity.Methods:We performed a retrospective chart review on a cohort of adult patients with long-term use (≥ 5 years cumulative) of HCQ between January 1st, 2011 to December 31st, 2018 from the Kaiser Permanente San Bernardino County and Riverside medical center areas in Southern California, USA. Patients were excluded if they had previously been diagnosed with retinopathy prior to hydroxychloroquine use, were deceased, or had incomplete OCT exam. Our primary endpoint was the prevalence of patients who developed retinal toxicity detected by OCT, and later confirmed by retinal specialist. Potential risk factors (age, duration of therapy, daily consumption per actual body weight, cumulative dose, confounding diseases and medication) for developing retinopathy were also evaluated. Univariable and multivariable logistic regression analyses were used to determine risk factors associated with retinal toxicity.Results:Among 676 patients exposed to more than 5 years of HCQ, the overall prevalence of retinal toxicity was 6.8%, and ranged from 2.5% to 22.2% depending on the age, weight-based dosing, duration of use and cumulative dose. Duration of therapy for 10 years or more increased risk of retinopathy by approximately 5 to 19 folds. Similarly, weight-based dose of 7 mg/kg/day or greater was assciated with increased risk of retinopathy by approximately 5 times. Patients with cumulative dose of 2000 grams or more had greater than 15 times higher risk of developing retinopathy. Duration of use for10 years or more (odd ratio 4.32, 95% CI 1.99 – 12.49), age (odd ratio 1.04; 95% CI 1.01 - 1.08), cumulative dose of more than 1500 g (odd ratio 7.4; 95% CI 1.40 – 39.04) and atherosclerosis of the aorta (odd ratio 2.59; 95% CI, 1.24 – 5.41) correlated with higher risk of retinal toxicity.Conclusion:The overall prevalence of retinopathy was 6.8%. Regular OCT screening, especially in patients with hydroxychloroquine use for more than 10 years, daily intake > 7 mg/kg, or cumulative dose > 1500 grams is important in detecting hydroxychloroquine-associated retinal toxicityReferences:[1]Hobbs HE. Sorsby A, & Freedman A. Retinopathy Following Chloroquine Therapy. The Lancet. 1959; 2(7101): 478-480.[2]Levy, G. D., Munz, S. J., Paschal, J., Cohen, H. B., Pince, K. J., & Peterson, T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis & Rheumatism: 1997; 40(8): 1482-1486.[3]Ding, H. J., Denniston, A. K., Rao, V. K., & Gordon, C. Hydroxychloroquine-related retinal toxicity. Rheumatology. 2016; 55(6): 957-967.[4]Stelton, C. R., Connors, D. B., Walia, S. S., & Walia, H. S. Hydrochloroquine retinopathy: characteristic presentation with review of screening. Clinical rheumatology. 2013; 32(6): 895-898.[5]Marmor, M. F., Kellner, U., Lai, T. Y., Melles, R. B., & Mieler, W. F. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016; 123(6): 1386-1394.[6]Melles, R. B., & Marmor, M. F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA ophthalmology. 2014; 132(12): 1453-1460.Disclosure of Interests:None declared


2021 ◽  
Author(s):  
Lisa Cummins ◽  
Irene Ebyarimpa ◽  
Nathan Cheetham ◽  
Victoria Tzortziou Brown ◽  
Katie Brennan ◽  
...  

AbstractBackgroundTo identify risk factors associated with increased risk of hospitalisation, intensive care unit (ICU) admission and mortality in inner North East London (NEL) during the first UK COVID-19 wave.MethodsMultivariate logistic regression analysis on linked primary and secondary care data from people aged 16 or older with confirmed COVID-19 infection between 01/02/2020-30/06/2020 determined odds ratios (OR), 95% confidence intervals (CI) and p-values for the association between demographic, deprivation and clinical factors with COVID-19 hospitalisation, ICU admission and mortality.ResultsOver the study period 1,781 people were diagnosed with COVID-19, of whom 1,195 (67%) were hospitalised, 152 (9%) admitted to ICU and 400 (23%) died. Results confirm previously identified risk factors: being male, or of Black or Asian ethnicity, or aged over 50. Obesity, type 2 diabetes and chronic kidney disease (CKD) increased the risk of hospitalisation. Obesity increased the risk of being admitted to ICU. Underlying CKD, stroke and dementia in-creased the risk of death. Having learning disabilities was strongly associated with increased risk of death (OR=4.75, 95%CI=(1.91,11.84), p=0.001). Having three or four co-morbidities increased the risk of hospitalisation (OR=2.34,95%CI=(1.55,3.54),p<0.001;OR=2.40, 95%CI=(1.55,3.73), p<0.001 respectively) and death (OR=2.61, 95%CI=(1.59,4.28), p<0.001;OR=4.07, 95% CI= (2.48,6.69), p<0.001 respectively).ConclusionsWe confirm that age, sex, ethnicity, obesity, CKD and diabetes are important determinants of risk of COVID-19 hospitalisation or death. For the first time, we also identify people with learning disabilities and multi-morbidity as additional patient cohorts that need to be actively protected during COVID-19 waves.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniele Melo Sardinha ◽  
Rosane do Socorro Pompeu de Loiola ◽  
Ana Lúcia da Silva Ferreira ◽  
Carmem Aliandra Freire de Sá ◽  
Yan Corrêa Rodrigues ◽  
...  

AbstractThe Brazilian Northern region registered a high incidence of COVID-19 cases, particularly in the state of Pará. The present study investigated the risk factors associated with the severity of COVID-19 in a Brazilian Amazon region of 100,819 cases. An epidemiological, cross-sectional, analytical and demographic study, analyzing data on confirmed cases for COVID-19 available at the Brazilian Ministry of Health's surveillance platform, was conducted. Variables such as, municipalities of residence, age, gender, signs and symptoms, comorbidities were included and associated with COVID-19 cases and outcomes. The spatial distribution was performed using the ArcGIS program. A total of 100,819 cases were evaluated. Overall, patients had the mean age of 42.3 years, were female (51.2%) and with lethality reaching 4.79% of cases. Main symptoms included fever (66.5%), cough (61.9%) and sore throat (39.8%). Regarding comorbidities, most of the patients presented cardiovascular disease (5.1%) and diabetes (4.2%). Neurological disease increased risk of death by nearly 15 times, followed by obesity (5.16 times) and immunodeficiency (5.09 time). The municipalities with the highest incidence rate were Parauapebas, Canaã dos Carajás and Jacareacanga. Similarity between the Lower Amazon, Marajó and Southwest mesoregions of Pará state were observed concerning the highest morbidity rates. The obtained data demonstrated that the majority of cases occurred among young adults, females, with the classic influenza symptoms and chronic diseases. Finally, data suggest that the highest incidences were no longer in the metropolitan region of the state. The higher lethality rate than in Brazil may be associated with the greater impacts of the disease in this Amazonian population, or factors associated with fragile epidemiological surveillance in the notification of cases of cure.


2020 ◽  
Author(s):  
Masahiro Kondo ◽  
Yuji Hotta ◽  
Karen Yamauchi ◽  
Akimasa Sanagawa ◽  
Hirokazu Komatsu ◽  
...  

Abstract Background: Novel agents such as proteasome inhibitors have been developed for several years to treat multiple myeloma. Although multiple myeloma is a low-risk disease for developing tumor lysis syndrome (TLS), treatment with these novel therapies might increase TLS risk. Previous studies, mostly case reports or case series, have reported bortezomib-induced TLS in patients with multiple myeloma. This study aimed to investigate risk factors associated with TLS development in multiple myeloma patients.Methods: We retrospectively investigated incidences of laboratory and clinical TLS (LTLS and CTLS, respectively) in patients who received primary therapy for treatment-naive, symptomatic multiple myeloma between May 2007 and January 2018. We used multivariate logistic regression analyses to evaluate the associations between TLS and several parameters previously reported to be associated with increased risk.Results: This study included 210 patients with multiple myeloma, of which ten (4.8%) had LTLS and seven (3.3%) had CTLS. The characteristics of the administered anticancer or prophylactic antihyperuricemic agents were similar between patients with and without TLS. Multivariate analyses revealed that TLS was most strongly associated with bortezomib-containing therapy (odds ratio = 3.40, P = 0.069), followed by male sex (odds ratio = 2.29, P = 0.153). In a subgroup analysis focused on men, treatment with bortezomib-containing therapy was significantly associated with increased risk of TLS (odds ratio = 8.51, P = 0.046).Conclusion: In the present study, we investigated the risk factors associated with TLS development in 210 multiple myeloma patients, which, to the best of our knowledge, is the largest number of patients reported to date. Furthermore, this study is the first to evaluate TLS risk factors in MM by adjusting for the effects of potential confounding factors in patients’ backgrounds. Consequently, we found that bortezomib-containing therapy increases the risk of TLS in male patients with multiple myeloma. TLS risk should be evaluated further in low-risk diseases such as multiple myeloma, since a significant number of novel therapies can achieve high antitumor responses.


PEDIATRICS ◽  
1980 ◽  
Vol 66 (4) ◽  
pp. 502-506 ◽  
Author(s):  
Susan Beckwitt Turkel ◽  
Marta E. Guttenberg ◽  
Diane Radovich Moynes ◽  
Joan E. Hodgman

In recent years kernicterus at autopsy has been observed in sick premature infants in the absence of markedly elevated levels of serum bilirubin. Potentiating factors have been suggested to explain kernicterus in such a setting. In order to establish which factors are associated with increased risk for kernicterus in these small babies, this retrospective matched control study was undertaken. Thirty-two infants with kernicterus at autopsy were matched for gestational age, birth weight, length of survival, and year of birth to 32 control infants without kernicterus. Multiple historical, clinical, and laboratory factors were compared, including therapy, sepsis, hypothermia, asphyxia as reflected by Apgar score, hematocrit, acidosis, hypercarbia, hypoxia, hypoglycemia, and hyperbilirubinemia. No statistically significant differences between the kernicteric and nonkernicteric infants were demonstrated for any of these factors, including peak total serum bilirubin levels. Multivariant analysis also failed to determine a group of factors associated with increased risk for kernicterus. It was not possible to separate those infants with and without kernicterus at autopsy on the basis of the clinical factors evaluated.


Author(s):  
Javier A Bustos ◽  
Gianfranco Arroyo ◽  
Robert H Gilman ◽  
Percy Soto-Becerra ◽  
Isidro Gonzales ◽  
...  

Abstract Background Neurocysticercosis is a major cause of acquired epilepsy. Larval cysts in the human brain eventually resolve and either disappear or leave a calcification that is associated with seizures. In this study, we assessed the proportion of calcification in parenchymal neurocysticercosis and risk factors associated with calcification. Methods Data for 220 patients with parenchymal NCC from 3 trials of antiparasitic treatment were assessed to determine what proportion of the cysts that resolved 6 months after treatment ended up in a residual calcification at 1 year. Also, we evaluated the risk factors associated with calcification. Results The overall proportion of calcification was 38% (188/497 cysts, from 147 patients). Predictors for calcification at the cyst level were cysts larger than 14 mm (risk ratio [RR], 1.34; 95% confidence interval [CI], 1.02–1.75) and cysts with edema at baseline (RR, 1.39; 95% CI, 1.05–1.85). At the patient level, having had more than 24 months with seizures (RR, 1.25; 95% CI, 1.08–1.46), mild antibody response (RR, 1.14; 95% CI, 1.002–1.27), increased dose albendazole regime (RR, 1.26; 95% CI, 1.14–1.39), lower doses of dexamethasone (RR, 1.36; 95% CI, 1.02–1.81), not receiving early antiparasitic retreatment (RR, 1.45; 95% CI, 1.08–1.93), or complete cure (RR, 1.48; 95% CI, 1.29–1.71) were associated with a increased risk of calcification. Conclusions Approximately 38% of parenchymal cysts calcify after antiparasitic treatment. Some factors associated with calcification are modifiable and may be considered to decrease or avoid calcification, potentially decreasing the risk for seizure relapses.


2013 ◽  
Vol 1 (1) ◽  
pp. 12 ◽  
Author(s):  
Ibrahim A. Yakasai ◽  
Imran O. Morhason-Bello

Pre-eclampsia (PE) is an important cause of maternal mortality. There have been several studies on risk factors assessment with conflicting reports across the globe on this disease; however, rigorous recent evaluation of these factors is uncommon in this region. The aim of the present study was to determine the risks factors in the early-onset PE in Aminu Kano Teaching Hospital (AKTH), Kano (Northern Nigeria). We conducted a case-control study in Nigeria between April 2009 and January 2010 to identify the risk factors associated with the early-onset PE in women attending antenatal clinic in AKTH. Information on socio-cultural characteristics, medical history, previous obstetrics history, level of stress at home, and type of family were obtained and recorded in a proforma designed for the study. Multiple logistic regression analysis was used to determine the risk factors for PE at 95% confidence level. Pregnant women with early-onset PE (150 in each case and control group). Risk factors associated with increased risk of early-onset PE were: history of pre-eclampsia/eclampsia (PE/E) in a previous pregnancy [adjusted odds ratio (AOR) 2.09]; exposure to passive smoking (AOR 1.34); inadequate antenatal supervision (AOR 15.21); family history of hypertension in one or more 1st-degree relative (AOR 8.92); living in a joint family (AOR 6.93); overweight (120% to 150% of pre-pregnancy ideal body weight, AOR 4.65). Risk factors among women in Northern Nigeria are similar to those reported from other studies. Good antenatal cares, early detection, reduction of stressful conditions at home are the most important preventive measures of early-onset severe PE among these women.


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