ABSTRACT
PURPOSE OF REVIEW: The pivotal phase III trials demonstrating efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF) excluded patients with important and common comorbidities, including obesity, advanced chronic kidney disease, cirrhosis, cancer and antiphospholipid antibody syndrome. Despite the lack of large prospective randomized control trials in these patient populations, the use of DOACs has led to a wealth of efficacy and safety data within these groups. RECENT FINDINGS: Retrospective studies, meta-analyses, national databases and pharmacokinetic data have shed light on the efficacy and safety of DOACs in these patient populations. Although DOACs should be avoided in those with high-risk triple positive antiphospholipid antibody syndrome, advanced cirrhosis, advanced kidney disease and intact gastrointestinal cancers, and used with caution in genitourinary cancers, their use extends beyond the inclusion criteria of the initial randomized control trials. SUMMARY: DOACs have revolutionized anticoagulant management and have become the cornerstone for VTE treatment and stroke prevention in NVAF. The decision to use DOACs must be individualized. Patient preference, underlying comorbidities and informed consent must always be considered when selecting the most appropriate anticoagulant.
Subject(s)
Anticoagulants , Venous Thromboembolism , Administration, Oral , Anticoagulants/adverse effects , Humans , Prospective Studies , Retrospective Studies , Venous Thromboembolism/drug therapyABSTRACT
Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250âµg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level.Patients >14 years who underwent SST from January 2010 to December 2017 were included. Pearson's chi-square cross-tabulation was used to identify individuals with inconsistent 30- and 60-minute serum cortisol test results. Logistic regression analysis was performed to predict normal responses based on the baseline cortisol value.Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394â±â286.58, 722â±â327.11, and 827â±â369.30ânmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (nâ=â72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550ânmol/L at 60 minutes. This particular subgroup's mean change (240ânmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152ânmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226ânmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST (P-valueâ<â.0001).Relying on a 60-minute cortisol level can identify all normal and abnormal responses, while relying on 30-minute cortisol level alone may produce false-positives. Additionally, a baseline cortisol level of ≥226ânmol/L is a reliable threshold for determining adequate adrenal function, particularly with a low pretest hypoadrenalism probability.