With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.
Outcomes in relapsed or refractory acute myeloid leukemia (AML) with unfavorable cytogenetic risk status are poor . One of these cytogenetic markers is the FMS-like tyrosine kinase 3 (FLT3), a cytokine receptor tyrosine kinase that is present in about 30% of patients with AML .
This international, multicenter phase 3 trial , randomized 247 patients with relapsed or refractory FLT3+ AML in a 2:1 fashion to gilteritinib, an oral and selective FLT3 inhibitor, or salvage chemotherapy. Results showed gilteritinib was superior to salvage chemotherapy in both the primary endpoints, overall survival (9.3 months vs. 5.6 months; HR for death 0.65, 95% CI 0.49-0.83) and full remission with full or partial hematologic recovery (34% vs. 15.3%; risk difference 18.6 percentage points, 95% CI 9.8-27.4). These results are consistent with a similarly designed trial , which also showed advantage of FLT3-directed therapy compared to salvage chemotherapy, however outcomes with this other agent (quizartinib) were not as robust and in contrast to gilteritinib, quizartinib is only used for one of the FLT3 variants.
Authors do warn that although these results are promising, they should not be overinterpreted, as there are important limitations, such as the relatively small sample size (especially for subgroup analysis) and the fact that very few subjects received FLT3-directed therapy during induction. Nonetheless, we might indeed be witnessing an “AML therapeutic revolution” .
Subclinical hypothyroidism is defined by increased thyroid-stimulating hormone (TSH) and normal free thyroxine levels (FT4). Previous literature  and current guidelines [8,9] recommend against the treatment of subclinical hypothyroidism, however adults 80 years and older have been underrepresented in previous studies .
To investigate whether adults 80 years or older would benefit from treatment, authors in this study  combined data from two randomized, double-blinded, placebo-controlled parallel-group clinical trials: the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial , and the Thyroid Hormone Replacement for Untreated Adults With Subclinical Hypothyroidism Trial (TRUST)  . A total of 251 participants (TSH range 4.6-17.6 mIU/L) were randomized in a 1:1 fashion to levothyroxine treatment or placebo. The co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness. This questionnaire ranges from 0-100 (higher scores mean more symptoms), and the minimal score difference for clinical importance is 9 .
At 1 year, hypothyroid symptoms scores between the intervention and placebo arm were not significantly different (scores decreased from 21.7 at baseline to 19.3 in the levothyroxine group, and 19.8 to 17.4 in the placebo group; p=0.53). Similarly, tiredness scores were not statistically different and increased from 25.5 to 28.2 in the levothyroxine group and 25.1 to 28.7 in the placebo group (p=0.96).
Despite some limitations, such as the lack of a pre-specified subgroup analysis in the high-symptom-burden group and more severely elevated TSH (values ranged from 4.6-12.5 mIU/L in the levothyroxine group), authors concluded that adults 80 years or older with subclinical hypothyroidism should not be routinely treated with levothyroxine.
For several years, the first-line treatment for major depressive disorder (MDD) has been pharmacologic therapy with second-generation antidepressants (SGAs) or cognitive behavioral therapy (CBT) . Despite this, it is estimated that fewer than a quarter of patients receive CBT . One factor that could account for the underuse of CBT is cost, as a single CBT session costs more than $100 , compared to commonly used SGAs, which cost less than $100 per year .
To further assess the cost-effectiveness of SGAs compared to CBT as initial treatment modality, authors used a previously described decision analytic model  to simulate the clinical and economic outcomes . Authors’ methodology was consistent with the 2013 Consolidation Health Economic Evaluation Reporting Standards . Results showed that there does not appear to be a substantial economic difference between SGAs and CBT, although the 1-year analysis favored SGAs (64-77% chance of being preferred) and the 5-year analysis favored CBT (73-77% chance of being preferred).
Authors did note a strong trend towards long-term savings with CBT, which despite not being statistically significant, could result in more than $1.5 billion in savings at 5 years. In short, authors concluded that given their clinical and economic similarities, the decision between SGAs and CBT for the initial treatment of MDD should continue to rely on patient-centered discussions that include preferences, CBT availability, and ability to afford up-front costs.
This study asked 382 participants 60 years or older with non-dialysis-dependent chronic kidney disease (CKD) stage 4 or 5 to answer what would be important to them in case they had a serious illness. Among them, 20% answered “live as long as possible,” compared to 33% for “focus on comfort.” One third of those who wanted to “focus on comfort” reported that “a life on dialysis would not be worth living,” compared to 5% of those who answered “live as long as possible” (p<0.001).
Nintedanib, an inhibitor of tyrosine kinase, has been shown to improve outcomes in idiopathic pulmonary fibrosis . In this double-blinded, placebo-controlled, phase 3 trial that included 663 patients , nintedanib was tested in a broad range of fibrosing lung diseases and was found to slow down the decline of the functional vital capacity (FVC) from 187.8ml per year to 80.8ml per year (p<0.001).
This retrospective cohort study used data from 1,206 subjects to correlate obstructive sleep apnea (OSA) severity and continuous positive airway pressure (CPAP) adherence with the incidence of type 2 diabetes (T2D). At a median follow-up of 7.3 years, investigators found that moderate and severe OSA increased the risk of T2D incidence (HR 2.01, 95% CI 1.06-3.81 for moderate; HR 2.62, 95% CI 1.40-4.93 for severe). The third of patients who used CPAP regularly appeared to have a lower T2D incidence, 3.41 versus 1.61 per 100 person-years.
This qualitative study that included 50 participants (11 hospitalists, 26 internal medicine residents, and 13 students) aimed to explore episodes of biased behaviors from patients towards physicians and trainees. It found that there is a wide range of biased behaviors that participants were exposed to including explicit racist, sexist, and homophobic comments, as well as more subtle microaggressions such as “jokes.” Uniformly, participants agreed that further training on how to respond in these situations, along with clear institutional policies, would be beneficial.
Dr. Alvaro Vargas is a third-year resident in internal medicine at NYU Langone Health
Peer reviewed by Christian Torres, MD, chief resident, internal medicine, NYU School of Medicine
Image courtesy of Wikimedia Commons
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