scholarly journals Association of subcutaneous or intravenous route of administration of casirivimab and imdevimab monoclonal antibodies with clinical outcomes in COVID-19.

2021 ◽  
Author(s):  
Erin K. McCreary ◽  
J. Ryan Bariola ◽  
Richard J. Wadas ◽  
Judith A. Shovel ◽  
Mary K. Wisniewski ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Risk Ratio ◽  
Intravenous Administration ◽  
Randomized Clinical Trials ◽  
Subcutaneous Administration ◽  
The United States ◽  
Risk Difference ◽  
Control Group ◽  
Intravenous Route ◽  
Adjusted Risk

Importance: Monoclonal antibody (mAb) treatment decreases hospitalization and death in outpatients with mild to moderate COVID 19; however, only intravenous administration has been evaluated in randomized clinical trials of treatment. Subcutaneous administration may expand outpatient treatment capacity and qualified staff available to administer treatment, but association with patient outcomes is understudied. Objective: To evaluate whether or not, i.) subcutaneous casirivimab and imdevimab treatment is associated with reduced 28 days hospitalization/death than non-treatment among mAb-eligible patients, and ii.) subcutaneous casirivimab and imdevimab treatment is clinically and statistically similar to intravenous casirivimab and imdevimab treatment. Design, Setting, and Participants: Prospective cohort study of outpatients in a learning health system in the United States with mild to moderate COVID 19 symptoms from July 14 to October 26, 2021 who were eligible for mAb treatment under emergency use authorization. A nontreated control group of eligible patients was also selected. Intervention: Subcutaneous injection or intravenous administration of the combined single dose of casirivimab 600mg and imdevimab 600mg. Main Outcomes and Measures: The primary outcome was the 28 day adjusted risk ratio or adjusted risk difference for hospitalization or death. Secondary outcomes included 28 day adjusted risk ratios/differences of hospitalization, death, composite endpoint of ED admission and hospitalization, and rates of adverse events. Results: Among 1,956 matched adults with mild to moderate COVID 19, patients who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalization/death of 3.4% (n=652) compared to 7.8% (n=1,304) in nontreated controls [risk ratio 0.44 (95% confidence interval: 0.28 to 0.68, p < .001)]. Among 2,185 patients treated with subcutaneous (n=969) or intravenous (n=1,216) casirivimab and imdevimab, the 28 day rate of hospitalization/death was 2.8% vs. 1.7%, respectively which resulted in an adjusted risk difference of 1.5% (95% confidence interval: -0.5% to 3.5%, p=.14). The 28 day adjusted risk differences (subcutaneous and intravenous) for death, ICU admission, and mechanical ventilation were 0.3% or less, although the 95% confidence intervals were wide. Conclusions and Relevance: Subcutaneously administered casirivimab and imdevimab is associated with reduced risk adjusted hospitalization or death amongst outpatients with mild to moderate COVID 19 compared to no treatment and indicates low adjusted risk difference compared to patients treated intravenously.

scholarly journals Febuxostat and Cardiovascular Events: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
John A. Cuenca ◽  
Javier Balda ◽  
Ana Palacio ◽  
Larry Young ◽  
Michael H. Pillinger ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Cardiovascular Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
The United States ◽  
Major Adverse Cardiovascular Events ◽  
Control Group ◽  
Embase Database ◽  
Cvd Mortality

Background. Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial. Objective. To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group. Methods. We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI). Results. Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03). Conclusions. Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.

Treatment with Antithrombin or Thrombomodulin and Mortality from Heatstroke-Induced Disseminated Intravascular Coagulation: A Nationwide Observational Study

2019 ◽  
Vol 45 (08) ◽  
pp. 760-766
Author(s):  
Hiroyuki Ohbe ◽  
Shunsuke Isogai ◽  
Taisuke Jo ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Treatment Group ◽  
Confidence Interval ◽  
Hospital Mortality ◽  
Disseminated Intravascular Coagulation ◽  
Risk Difference ◽  
Control Group ◽  
Robust Analysis ◽  
Intravascular Coagulation ◽  
Doubly Robust ◽  
Inpatient Database

AbstractHeatstroke-induced disseminated intravascular coagulation represents potential targets for specific intensive treatments. However, the effect of antithrombin or thrombomodulin treatment remains uncertain. Using a large nationwide inpatient database in Japan, this study aimed to evaluate whether treatment with antithrombin or thrombomodulin could reduce mortality among patients with heatstroke-induced disseminated intravascular coagulation. Using the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2017, we identified heatstroke patients who developed disseminated intravascular coagulation. We allocated patients who started treatment with antithrombin or thrombomodulin within 2 days after admission to the treatment group and allocated others to the control group. A primary outcome was in-hospital mortality. We used a doubly robust analysis to ensure the robustness of our findings. We also conducted two sensitivity analyses for thrombomodulin versus others and antithrombin versus others. We identified 1,606 eligible patients during the 81-month study period. Of these, 556 (35%) received antithrombin or thrombomodulin. The doubly robust analysis demonstrated that in-hospital mortality was significantly lower among patients in the treatment group than among those in the control group (risk difference −6.5%; 95% confidence interval: −12 to −1.4%). In-hospital mortality was significantly lower in patients with thrombomodulin than in others (risk difference −5.5%; 95% confidence interval: −9.5 to −1.6%). There was no significant difference in in-hospital mortality between patients with antithrombin and others (risk difference −4.2%; 95% confidence interval: −9.3 to 0.9%). Treatment with recombinant human thrombomodulin may be associated with lower in-hospital mortality among patients with heatstroke-induced disseminated intravascular coagulation.

scholarly journals β-Blockers, Pneumonia, and Outcome After Ischemic Stroke

Stroke ◽  
2015 ◽  
Vol 46 (5) ◽  
pp. 1269-1274 ◽  
Author(s):  
Marek Sykora ◽  
Pavel Siarnik ◽  
Jennifer Diedler ◽  
K.R. Lees ◽  
A. Alexandrov ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Confidence Interval ◽  
Functional Outcome ◽  
Risk Ratio ◽  
Infectious Complications ◽  
Modified Rankin Scale ◽  
Adjusted Risk ◽  
Reduced Frequency ◽  
Adjusted Risk Ratio ◽  
Β Blocker

Background and Purpose— Increased sympathetic drive after stroke is involved in the pathophysiology of several complications including poststroke immunudepression. β-Blocker (BB) therapy has been suggested to have neuroprotective properties and to decrease infectious complications after stroke. We aimed to examine the effects of random pre- and on-stroke BB exposure on mortality, functional outcome, and occurrence of pneumonia after ischemic stroke. Methods— Data including standard demographic and clinical variables as well as prestroke and on-stroke antihypertensive medication, incidence of pneumonia, functional outcome defined using modified Rankin Scale and mortality at 3 months were extracted from the Virtual International Stroke Trials Archive. For statistical analysis multivariable Poisson regression was used. Results— In total, 5212 patients were analyzed. A total of 1155 (22.2%) patients were treated with BB before stroke onset and 244 (4.7%) patients were newly started with BB in the acute phase of stroke. Mortality was 17.5%, favorable outcome (defined as modified Rankin Scale, 0–2) occurred in 58.2% and pneumonia in 8.2% of patients. Prestroke BB showed no association with mortality. On-stroke BB was associated with reduced mortality (adjusted risk ratio, 0.63; 95% confidence interval, 0.42–0.96). Neither prestroke BB nor on-stroke BB showed an association with functional outcome. Both prestroke and on-stroke BB were associated with reduced frequency of pneumonia (adjusted risk ratio, 0.77; 95% confidence interval, 0.6–0.98 and risk ratio, 0.49; 95% confidence interval, 0.25–0.95). Conclusions— In this large nonrandomized comparison, on-stroke BB was associated with reduced mortality. Prestroke and on-stroke BB were inversely associated with incidence of nosocomial pneumonia. Randomized trials investigating the potential of β-blockade in acute stroke may be warranted.

Intravenous Streptokinase in Acute Myocardial Infarction

1983 ◽  
Vol 17 (5) ◽  
pp. 367-368
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Trials ◽  
Chest Pain ◽  
Intravenous Administration ◽  
Randomized Clinical Trials ◽  
Intravenous Route ◽  
Intravenous Streptokinase ◽  
Intracoronary Streptokinase ◽  
Percent Decrease

Intracoronary streptokinase has been reported to be successful in producing coronary recanalization and lowered morbidity and mortality in acute myocardial infarction patients, when administered shortly after the onset of chest pain. However, intracoronary administration of streptokinase is not practical for most hospitals at present, and intravenous administration would enable treatment of larger numbers of patients and enable the drug to be administered earlier than by the intracoronary route. Available studies have suggested benefits of the intravenous route and results of randomized clinical trials indicate an approximately 20-percent decrease in mortality after intravenous use. Intravenous streptokinase after acute myocardial infarction warrants further investigation.

scholarly journals Association between Dietary Salt Intake and Progression in the Gastric Precancerous Process

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 467 ◽  
Author(s):  
Susan Thapa ◽  
Lori A. Fischbach ◽  
Robert Delongchamp ◽  
Mohammed F. Faramawi ◽  
Mohammed Orloff
Keyword(s):  
Gastric Cancer ◽  
Confidence Interval ◽  
Risk Ratio ◽  
Salt Intake ◽  
Precancerous Lesions ◽  
Urinary Sodium ◽  
Adjusted Risk ◽  
Adjusted Risk Ratio ◽  
Increased Risk ◽  
H Pylori

Gastric cancer is the third leading cause of cancer mortality worldwide. Studies investigating the effect of salt on gastric cancer have mainly used self-reported measures, which are not as accurate as sodium/creatinine ratios because individuals may not know the amount of salt in their food. Using data from a prospective cohort study, we investigated the effect of salt intake on progression to gastric precancerous lesions. Salt intake was estimated by urinary sodium/creatinine ratios, self-reported frequencies of adding salt to food, and total added table salt. We repeated the analyses among groups with and without Helicobacter pylori infection. We did not observe a positive association between salt intake, measured by urinary sodium/creatinine ratio, and overall progression in the gastric precancerous process (adjusted risk ratio (RR): 0.94; 95% confidence interval (CI) 0.76–1.15). We did observe an association between salt intake and increased risk for progression to dysplasia or gastric cancer overall (adjusted risk ratio (RR): 1.32; 95% confidence interval (CI): 0.96–1.81), especially among those who continued to have H. pylori infection at the five-month follow-up (adjusted RR: 1.53; 95% CI: 1.12–2.09), and among those who had persistent H. pylori infection over 12 years (adjusted RR: 1.49; 95% CI: 1.09–2.05). Salt intake may increase the risk of gastric dysplasia or gastric cancer in individuals with H. pylori infection.

scholarly journals More Screening or More Disease? Gonorrhea Testing and Positivity Patterns Among Men in 3 Large Clinical Practices in Massachusetts, 2010–2017

2020 ◽  
Author(s):  
Sarah J Willis ◽  
Heather Elder ◽  
Noelle Cocoros ◽  
Jessica Young ◽  
Julia L Marcus ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Positive Result ◽  
Risk Ratio ◽  
The United States ◽  
Clinical Practices ◽  
Clinical Encounters ◽  
Binomial Regression ◽  
Testing Patterns ◽  
Test Result ◽  
Annual Risk

Abstract Background Gonorrhea diagnosis rates in the United States increased by 75% during 2009–2017, predominantly in men. It is unclear whether the increase among men is being driven by more screening, an increase in the prevalence of disease, or both. We sought to evaluate changes in gonorrhea testing patterns and positivity among men in Massachusetts. Methods The analysis included men (aged ≥15 years) who received care during 2010–2017 in 3 clinical practice groups. We calculated annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive result, among men tested. Log-binomial regression models were used to examine trends in these outcomes. We adjusted for clinical and demographic characteristics that may influence the predilection to test and probability of gonorrhea disease. Results On average, 306 348 men had clinical encounters each year. There was a significant increase in men with ≥1 gonorrhea test from 2010 (3.1%) to 2017 (6.4%; adjusted annual risk ratio, 1.12; 95% confidence interval, 1.12–1.13). There was a significant, albeit lesser, increase in the percentage of tested men with ≥1 positive result (1.0% in 2010 to 1.5% in 2017; adjusted annual risk ratio, 1.07; 95% confidence interval, 1.04–1.09). Conclusions We estimated significant increases in the annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive gonorrhea test result between 2010 and 2017. These results suggest that observed increases in gonorrhea rates could be explained by both increases in screening and the prevalence of gonorrhea.

scholarly journals Association Between Industry Marketing Payments and Prescriptions for PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitors in the United States

2021 ◽  
Author(s):  
Kosuke Inoue ◽  
Jose F. Figueroa ◽  
Colette DeJong ◽  
Yusuke Tsugawa ◽  
E. John Orav ◽  
...  
Keyword(s):  
Primary Care ◽  
Risk Ratio ◽  
Primary Care Physicians ◽  
Clinical Decision Making ◽  
Density Lipoprotein ◽  
The United States ◽  
Prior Authorization ◽  
Proprotein Convertase ◽  
Adjusted Risk ◽  
Adjusted Risk Ratio

Background: Marketing payments from the pharmaceutical industry to physicians have come under scrutiny due to their potential to influence clinical decision-making. Two proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were approved by the US Food and Drug Administration in 2015 for reducing low-density lipoprotein cholesterol in high-risk patients, but their initial uptake was limited due to their high-cost and stringent prior authorization requirements. We sought to investigate the association between industry marketing and early adoption of PCSK9i among US physicians. Methods: We used nationwide databases of primary care physicians, cardiologists, and endocrinologists treating Medicare beneficiaries to examine the association between PCSK9i-related marketing payments in 2016 and the number of filled PCSK9i prescriptions in 2017, after adjusting for physician characteristics. In subgroup analyses, we stratified our analyses by physician specialty and prior experience with prescribing PCSK9i. Results: Among 209 840 physicians included in this analysis, 49 341 (24%) physicians received 292 941 PCSK9i-related marketing payments in 2016. The total value of these payments was $19 million, with a median payment of $61 per physician (interquartile range, $25–$132). Most payments (95%) were for meals, with a median of $14 per meal. The receipt of PCSK9i-related payments in 2016 was associated with increased PCSK9i prescription in 2017 (adjusted risk ratio, 3.18 [95% CI, 2.95–3.42]). This association was larger among primary care physicians (adjusted risk ratio, 6.67 [95% CI, 5.87–7.57]) than cardiologists (adjusted risk ratio, 2.00 [95% CI, 1.84–2.16]) and endocrinologists (adjusted risk ratio, 4.06 [95% CI, 2.95–5.59]). The association was observed across all types of payments. Conclusions: At a time when few physicians had experience with prescribing PCSK9i under strict prior authorization requirements, industry marketing payments to physicians for PCSK9i, predominantly in the form of meals, were associated with increased PCSK9i prescription in the subsequent year.

scholarly journals Trends of Ruptured and Unruptured Aneurysms Treatment in the United States in Post‐ISAT Era: A National Inpatient Sample Analysis

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Mohamed M. Salem ◽  
Georgios A. Maragkos ◽  
Santiago Gomez‐Paz ◽  
Luis C. Ascanio ◽  
Long H. Ngo ◽  
...  
Keyword(s):  
Relative Risk ◽  
Risk Ratio ◽  
Intracranial Aneurysms ◽  
The United States ◽  
Relative Risk Ratio ◽  
Control Group ◽  
National Inpatient Sample ◽  
Multinomial Regression ◽  
Unruptured Aneurysms ◽  
Unruptured Intracranial Aneurysms

Background The ISAT (International Subarachnoid Aneurysm Trial) has generated a paradigm shift towards endovascular treatment for intracranial aneurysms but remains unclear if this has led to a true reduction in the risk for aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between the treatment burden of unruptured and ruptured aneurysms in the post‐ISAT era. Methods and Results Admissions data from the National Inpatient Sample (2004–2014) were extracted, including patients with a primary diagnosis of aSAH or unruptured intracranial aneurysms treated by clipping or coiling. Within each year, this combined group was randomly matched to non‐aneurysmal control group, based on age, sex, and Elixhauser comorbidity index. Multinomial regression was performed to calculate the relative risk ratio of undergoing treatment for either ruptured or unruptured aneurysms in comparison with the reference control group, adjusted for time. After adjusting for National Inpatient Sample sampling effects, 243 754 patients with aneurysm were identified, 174 580 (71.6%) were women; mean age, 55.4±13.2 years. A total of 121 882 (50.01%) patients were treated for unruptured aneurysms, 79 627 (65.3%) endovascularly and 42 256 (34.7%) surgically. A total of 121 872 (49.99%) patients underwent procedures for aSAH, 68 921 (56.6%) endovascular, and 52 951 (43.5%) surgically. Multinomial regression revealed a significant year‐to‐year decrease in aSAH procedures compared with the control group of non‐aneurysmal hospitalizations (relative risk ratio, 0.963 per year; P <0.001), while there was no statistical significance for unruptured aneurysms procedures (relative risk ratio, 1.012 per year; P =0.35). Conclusions With each passing year, there is a significant decrease in relative risk ratio of undergoing treatment for aSAH, concomitant with a stable annual risk of undergoing treatment for unruptured intracranial aneurysms.

Association of maternal prenatal acetaminophen use with the risk of attention deficit/hyperactivity disorder in offspring: A meta-analysis

2019 ◽  
Vol 53 (3) ◽  
pp. 195-206 ◽  
Author(s):  
Xiaoyun Gou ◽  
Yan Wang ◽  
Ying Tang ◽  
Yi Qu ◽  
Jun Tang ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Confidence Interval ◽  
Risk Ratio ◽  
Attention Deficit ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Sample Population ◽  
Adjusted Risk ◽  
Hyperactivity Disorder ◽  
Disorder Risk

Background: Acetaminophen is a widely used medication for fever and pain management during pregnancy. However, recent studies have found a possible connection between maternal prenatal acetaminophen use and attention deficit/hyperactivity disorder in children. Objective: We aimed to explore the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. Data sources: PubMed, Embase, Web of Science and Cochrane Library were searched from their initial publications through November 2018 for studies. Study selection: We included all studies that examined the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring if the authors reported odds ratios, risk ratios, hazard ratios, regression coefficient, standard error and 95% confidence intervals. Data extraction and synthesis: Two reviewers independently extracted data on the definition of exposure and outcome, exposed, non-exposed and total number of participants in the sample population, adjusted potential confounders and outcome parameters. Study quality was also assessed. Results: Eight cohort studies with a total of 244,940 participants were included. Maternal exposure to acetaminophen during pregnancy increased the risk of attention deficit/hyperactivity disorder in offspring with a pooled adjusted risk ratio of 1.25 (95% confidence interval = [1.17, 1.34]). Children exposed prenatally to acetaminophen in the third trimester seemed to have the greatest risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.26; 95% confidence interval = [1.08, 1.47]). In addition, a longer duration of maternal acetaminophen use during pregnancy was correlated with a higher risk ratio. Children whose mothers used acetaminophen for 28 or more days during gestation had a higher risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.63; 95% confidence interval = [1.23, 2.16]). Conclusion: There is an association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. The timing and duration of acetaminophen use during pregnancy may have a major effect on the risk of attention deficit/hyperactivity disorder.

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