Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study

Abstract Objective To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. Design Observational cohort study. Setting Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. Participants All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. Main outcome measures The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. Results Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. Conclusions Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

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Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States

10.1101/2020.12.09.20246579 ◽

2020 ◽

Author(s):

Christopher T Rentsch ◽

Joshua A Beckman ◽

Laurie Tomlinson ◽

Walid F Gellad ◽

Charles Alcorn ◽

...

Keyword(s):

United States ◽

Cohort Study ◽

The United States ◽

Early Initiation ◽

Sensitivity Analyses ◽

Inpatient Mortality ◽

Risk Of Death ◽

Subcutaneous Heparin ◽

Therapeutic Anticoagulation ◽

Prophylactic Anticoagulation

AbstractImportanceDeaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19.ObjectiveTo evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19.DesignObservational cohort study.SettingNationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States.ParticipantsAll patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation.ExposuresProphylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants.Main Outcomes and Measures30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation.ResultsOf 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses.Conclusions and RelevanceEarly initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.

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Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

BMC Cancer ◽

10.1186/s12885-021-07790-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Daniel C. Beachler ◽

Cynthia de Luise ◽

Aziza Jamal-Allial ◽

Ruihua Yin ◽

Devon H. Taylor ◽

...

Keyword(s):

Breast Cancer ◽

United States ◽

Pulmonary Embolism ◽

Cohort Study ◽

Real World ◽

The United States ◽

Elevated Risk ◽

Breast Cancer Patients ◽

Increased Risk ◽

Serious Infections

Abstract Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

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Iron Packaging Regulations in the United States and Pediatric Morbidity: A Retrospective Cohort Study

Clinical Pediatrics ◽

10.1177/0009922819901010 ◽

2020 ◽

Vol 59 (4-5) ◽

pp. 375-379 ◽

Cited By ~ 1

Author(s):

James B. Leonard ◽

Elizabeth Quaal Hines ◽

Wendy Klein-Schwartz

Keyword(s):

United States ◽

Cohort Study ◽

Confidence Interval ◽

Retrospective Cohort Study ◽

Odds Ratio ◽

Retrospective Cohort ◽

Early Time ◽

The United States ◽

Morbidity And Mortality ◽

Pediatric Morbidity

Iron poisoning was a leading cause of pediatric morbidity and mortality. We sought to assess whether the removal of strict iron packaging requirements in 2003 resulted in an increase in iron-related morbidity and mortality in pediatric exposures. We performed a retrospective cohort study utilizing the National Poison Data System from 2000 to 2017. A total of 4110 exposures met inclusion criteria: 847 from before (2000-2003) and 3263 after removal of unit-dose package regulations (2004-2017). The incidence of any marker of severity (7.2% vs 3.8%; odds ratio = 0.51, 95% confidence interval = 0.37-0.69) and frequency of deferoxamine use were both higher in the early time period (2.6% vs 1.0%; odds ratio = 0.38, 95% confidence interval = 0.22-0.66). There was no difference in the frequency of key serious effects (acidosis, elevated transaminases, hypotension). Despite removal of iron packaging regulations in the United States, there continues to be a decrease in the incidence of severe iron exposures in children.

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Race and Cancer-Associated Venous Thromboembolism in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Blood ◽

10.1182/blood.v126.23.3551.3551 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3551-3551

Author(s):

Daniel Douce ◽

Nels Olson ◽

Mary Cushman ◽

Pamela L Lutsey ◽

Suzanne Judd ◽

...

Keyword(s):

United States ◽

Venous Thromboembolism ◽

Confidence Interval ◽

Trauma Surgery ◽

The United States ◽

Southeastern Us ◽

Hazard Ratios ◽

Increased Risk ◽

Male Sex ◽

Blacks And Whites

Abstract Introduction: Venous thromboembolism (VTE) is classified as provoked (associated with surgery, hospitalization, trauma, or cancer) and unprovoked events. Whether provoked, unprovoked or cancer-associated VTE differs by age, sex, race, or region in the United States is poorly understood. Methods: VTE events were ascertained in 30,183 individuals in the REGARDS cohort enrolled between 2003-2007 in the contiguous United States. Participants were enrolled in their homes, with a goal of 50% of the cohort being black, female, and living in the southeastern US. VTE events were identified by telephone interviews, review of hospitalizations and deaths and validated by physician review of medical records. Cancer-associated VTE (CA-VTE) was defined as a VTE associated with active cancer or chemotherapy in the last 90 days. Non-cancer, provoked VTE was defined as a VTE that was preceded within 90 days by major trauma, surgery, or hospitalization. Unprovoked VTE was defined as having none of the above risk factors. The associations of age, sex, race and region with cancer-associated, provoked, and unprovoked VTE were analyzed by chi square analyses and Cox proportional hazard ratios that were adjusted for age, sex, race, region and obesity. Results: Overall, 332 VTE events occurred over a mean of 4.7 years follow up. Of these, 163 events (49.1%) were provoked, 47 (14.2%) were CA-VTE. The proportion of unprovoked to provoked VTE did not differ by age (120 to 104 in those older than 65, 49 to 59 for those under 65, p=0.16) sex (98 to 90 in men, 71 to 73 in women, p=0.61), race (61 to 62 in blacks, 108 to 101 in whites, p=0.71) or region (89 to 88 in the Southeast, 80 to 75 for the rest of the country p=0.81); however CA-VTE was significantly less common in blacks (11 of 123, 8.9%) than whites (36 of 209, 17.2%) (p=0.04). While the overall risk of VTE was similar in blacks and whites, blacks had a lower risk of CA-VTE than whites (Hazard Ratio (HR) 0.38, 95% Confidence Interval (CI) 0.18-0.77). Increased age and male sex were associated with an increased risk for all-cause VTE and unprovoked VTE with a trend for male sex and increased risk for provoked VTE (Table). However, men had no increased risk of CA-VTE compared to women (0.85 95% CI 0.46-1.55). Discussion: The proportion of provoked versus unprovoked VTE events did not differ by age, sex, race or region in REGARDS, though blacks had a lower proportion of CA-VTE than whites. Men overall had a higher risk of VTE than women, but there was no increased risk for CA-VTE in men. Blacks and whites had a similar risk of VTE overall, however blacks had a lower incidence of CA-VTE than whites. Possible reasons for our findings include shorter survival after a diagnosis of cancer, different cancer types or treatments, or differential ascertainment of VTE by race or sex. These findings highlight the need to understand how sex and race impact VTE incidence so we can best prevent VTE in everyone. Table. Hazard Ratios for different VTE subtypes by Age, Sex, and Race (95% Confidence Interval) All VTE Unprovoked VTE Provoked VTE Cancer-Associated VTE Age (per SD, 9.4 years) 1.61 (1.43-1.80) 1.70 (1.44-1.99) 1.52 (1.29-1.79) 1.48 (1.09-2.02) Male Sex 1.42 (1.13-1.78) 1.52 (1.11-2.09) 1.32 (0.96-1.82) 0.85 (0.47-1.55) Black versus White Race 0.90 (0.71-1.13) 0.84 (0.61-1.16) 0.96 (0.69-1.34) 0.38 (0.18-0.77) Disclosures No relevant conflicts of interest to declare.

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The relationship between anxiety, health, and potential stressors among adults in the United States during the COVID-19 pandemic

10.1101/2020.10.30.20221440 ◽

2020 ◽

Cited By ~ 1

Author(s):

Angela M Parcesepe ◽

McKaylee Robertson ◽

Amanda Berry ◽

Andrew Maroko ◽

Rebecca Zimba ◽

...

Keyword(s):

United States ◽

Cohort Study ◽

Prevalence Ratio ◽

The United States ◽

Anxiety Symptoms ◽

Poisson Models ◽

Increased Risk ◽

The Relationship ◽

Severe Anxiety ◽

The U.S

ABSTRACTObjectiveTo estimate the prevalence of anxiety symptoms and the association between moderate or severe anxiety symptoms and health and potential stressors among adults in the U.S. during the COVID-19 pandemicMethodsThis analysis includes data from 5,250 adults in the Communities, Households and SARS/CoV-2 Epidemiology (CHASING) COVID Cohort Study surveyed in April 2020. Poisson models were used to estimate the association between moderate or severe anxiety symptoms and health and potential stressors among U.S. adults during the COVID-19 pandemic.ResultsGreater than one-third (35%) of participants reported moderate or severe anxiety symptoms. Having lost income due to COVID-19 (adjusted prevalence ratio [aPR] 1.27 (95% CI 1.16, 1.30), having recent COVID-like symptoms (aPR 1.17 (95% CI 1.05, 1,31), and having been previously diagnosed with depression (aPR 1.49, (95% CI 1.35, 1.64) were positively associated with anxiety symptoms.ConclusionsAnxiety symptoms were common among adults in the U.S. during the COVID-19 pandemic. Strategies to screen and treat individuals at increased risk of anxiety, such as individuals experiencing financial hardship and individuals with prior diagnoses of depression, should be developed and implemented.

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Dialysis Facility Profit Status and Early Steps in Kidney Transplantation in the Southeastern United States

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.17691120 ◽

2021 ◽

pp. CJN.17691120

Author(s):

Laura J. McPherson ◽

Elizabeth R. Walker ◽

Yi-Ting Hana Lee ◽

Jennifer C. Gander ◽

Zhensheng Wang ◽

...

Keyword(s):

United States ◽

Cohort Study ◽

Kidney Transplantation ◽

Confidence Interval ◽

Kidney Failure ◽

The United States ◽

For Profit ◽

Transplant Center ◽

Dialysis Facility ◽

Profit Status

Background and objectivesDialysis facilities in the United States play a key role in access to kidney transplantation. Previous studies reported that patients treated at for-profit facilities are less likely to be waitlisted and receive a transplant, but their effect on early steps in the transplant process is unknown. The study’s objective was to determine the association between dialysis facility profit status and critical steps in the transplantation process in Georgia, North Carolina, and South Carolina.Design, setting, participants, & measurementsIn this retrospective cohort study, we linked referral and evaluation data from all nine transplant centers in the Southeast with United States Renal Data System surveillance data. The cohort study included 33,651 patients with kidney failure initiating dialysis from January 1, 2012 to August 31, 2016. Patients were censored for event (date of referral, evaluation, or waitlisting), death, or end of study (August 31, 2017 for referral and March 1, 2018 for evaluation and waitlisting). The primary exposure was dialysis facility profit status: for profit versus nonprofit. The primary outcome was referral for evaluation at a transplant center after dialysis initiation. Secondary outcomes were start of evaluation at a transplant center after referral and waitlisting.ResultsOf the 33,651 patients with incident kidney failure, most received dialysis treatment at a for-profit facility (85%). For-profit (versus nonprofit) facilities had a lower cumulative incidence difference for referral within 1 year of dialysis (−4.5%; 95% confidence interval, −6.0% to −3.2%). In adjusted analyses, for-profit versus nonprofit facilities had lower referral (hazard ratio, 0.84; 95% confidence interval, 0.80 to 0.88). Start of evaluation within 6 months of referral (−1.0%; 95% confidence interval, −3.1% to 1.3%) and waitlisting within 6 months of evaluation (1.0%; 95% confidence interval, −1.2 to 3.3) did not meaningfully differ between groups.ConclusionsFindings suggest lower access to referral among patients dialyzing in for-profit facilities in the Southeast United States, but no difference in starting the evaluation and waitlisting by facility profit status.

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Abortion, substance abuse and mental health in early adulthood: Thirteen-year longitudinal evidence from the United States

SAGE Open Medicine ◽

10.1177/2050312116665997 ◽

2016 ◽

Vol 4 ◽

pp. 205031211666599 ◽

Cited By ~ 11

Author(s):

Donald Paul Sullins

Keyword(s):

Mental Health ◽

United States ◽

Mental Disorders ◽

Confidence Interval ◽

Pregnancy Outcomes ◽

Pregnancy Loss ◽

Early Adulthood ◽

The United States ◽

Mental Health Disorder ◽

Increased Risk

Objective: To examine the links between pregnancy outcomes (birth, abortion, or involuntary pregnancy loss) and mental health outcomes for US women during the transition into adulthood to determine the extent of increased risk, if any, associated with exposure to induced abortion. Method: Panel data on pregnancy history and mental health history for a nationally representative cohort of 8005 women at (average) ages 15, 22, and 28 years from the National Longitudinal Study of Adolescent to Adult Health were examined for risk of depression, anxiety, suicidal ideation, alcohol abuse, drug abuse, cannabis abuse, and nicotine dependence by pregnancy outcome (birth, abortion, and involuntary pregnancy loss). Risk ratios were estimated for time-dynamic outcomes from population-averaged longitudinal logistic and Poisson regression models. Results: After extensive adjustment for confounding, other pregnancy outcomes, and sociodemographic differences, abortion was consistently associated with increased risk of mental health disorder. Overall risk was elevated 45% (risk ratio, 1.45; 95% confidence interval, 1.30–1.62; p < 0.0001). Risk of mental health disorder with pregnancy loss was mixed, but also elevated 24% (risk ratio, 1.24; 95% confidence interval, 1.13–1.37; p < 0.0001) overall. Birth was weakly associated with reduced mental disorders. One-eleventh (8.7%; 95% confidence interval, 6.0–11.3) of the prevalence of mental disorders examined over the period were attributable to abortion. Conclusion: Evidence from the United States confirms previous findings from Norway and New Zealand that, unlike other pregnancy outcomes, abortion is consistently associated with a moderate increase in risk of mental health disorders during late adolescence and early adulthood.

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A large outbreak of scombroid fish poisoning associated with eating escolar fish (Lepidocybium flavobrunneum)

Epidemiology and Infection ◽

10.1017/s095026880400322x ◽

2004 ◽

Vol 133 (1) ◽

pp. 29-33 ◽

Cited By ~ 24

Author(s):

K. A. FELDMAN ◽

S. B. WERNER ◽

S. CRONAN ◽

M. HERNANDEZ ◽

A. R. HORVATH ◽

...

Keyword(s):

United States ◽

Cohort Study ◽

Relative Risk ◽

Confidence Interval ◽

Retrospective Cohort ◽

The United States ◽

Case Definition ◽

Duration Of Symptoms ◽

Fish Poisoning ◽

Large Outbreak

In August 2003, an outbreak of scombroid fish poisoning occurred at a retreat centre in California, USA. In a retrospective cohort study, 42 (75%) of the 56 dinner attendees who ate escolar fish (Lepidocybium flavobrunneum) met the case definition. Individuals who ate at least 2 oz of fish were 1·5 times more likely to develop symptoms than those who ate less (relative risk 1·5, 95% confidence interval 0·9–2·6), and to develop more symptoms (median 7 vs. 3 symptoms, P=0·03). Patients who took medicine had a longer duration of symptoms than those who did not (median 4 vs. 1·5 h, P=0·05), and experienced a greater number of symptoms (median 8 vs. 3 symptoms, P=0·0002). Samples of fish contained markedly elevated histamine levels (from 2000 to 3800 ppm). This is one of the largest reported outbreaks of scombroid fish poisoning in the United States and was associated with a rare vehicle for scombroid fish poisoning, escolar.

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Hemorrhage in patients with polycythemia vera receiving aspirin with an anticoagulant: a prospective, observational study

Haematologica ◽

10.3324/haematol.2021.279032 ◽

2021 ◽

Author(s):

Jeffrey I. Zwicker ◽

Dilan Paranagama ◽

David S. Lessen ◽

Philomena M. Colucci ◽

Michael R. Grunwald

Keyword(s):

United States ◽

Observational Study ◽

Confidence Interval ◽

Polycythemia Vera ◽

Prospective Observational Study ◽

The United States ◽

Increased Risk ◽

Adjusted Rate ◽

Risk Of Hemorrhage

Polycythemia vera (PV) is associated with increased risk of thrombosis and hemorrhage. Aspirin, recommended for primary thromboprophylaxis, is often combined with anticoagulants during management of acute thrombotic events. The safety of dual antiplatelet and anticoagulant therapy is not established in PV. In a prospective, observational study, 2510 patients with PV were enrolled at 227 sites in the United States. Patients were monitored for the development of hemorrhage and thrombosis after enrollment. A total of 1602 patients with PV received aspirin with median (range) follow-up of 2.4 (0-3.6) years. The exposure-adjusted rate of all hemorrhages in patients receiving aspirin alone was 1.40 per 100 patient-years (95% confidence interval [CI]: 0.99-1.82). The combination of aspirin plus anticoagulant was associated with an incidence of hemorrhage of 6.75 per 100 patient-years (95% CI: 3.04-10.46). The risk of hemorrhage was significantly greater in patients receiving the combination of aspirin and anticoagulant compared with aspirin alone (total hemorrhages, hazard ratio [HR]: 5.83; 95% CI: 3.36-10.11; P

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Increase in Suicidal Thinking During COVID-19

Clinical Psychological Science ◽

10.1177/2167702621993857 ◽

2021 ◽

pp. 216770262199385

Author(s):

Rebecca G. Fortgang ◽

Shirley B. Wang ◽

Alexander J. Millner ◽

Azure Reid-Russell ◽

Anna L. Beukenhorst ◽

...

Keyword(s):

United States ◽

Confidence Interval ◽

Social Isolation ◽

Odds Ratio ◽

The United States ◽

Suicidal Thinking ◽

Increased Risk ◽

Monitoring Study ◽

Before And After ◽

National Emergency

There is concern that the COVID-19 pandemic may cause increased risk of suicide. In the current study, we tested whether suicidal thinking has increased during the COVID-19 pandemic and whether such thinking was predicted by increased feelings of social isolation. In a sample of 55 individuals recently hospitalized for suicidal thinking or behaviors and participating in a 6-month intensive longitudinal smartphone monitoring study, we examined suicidal thinking and isolation before and after the COVID-19 pandemic was declared a national emergency in the United States. We found that suicidal thinking increased significantly among adults (odds ratio [ OR] = 4.01, 95% confidence interval [CI] = [3.28, 4.90], p < .001) but not adolescents ( OR = 0.84, 95% CI = [0.69, 1.01], p = .07) during the onset of the COVID-19 pandemic. Increased feelings of isolation predicted suicidal thinking during the pandemic phase. Given the importance of social distancing policies, these findings support the need for digital outreach and treatment.

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