Citations

This review article examines evidence supporting the use of oral therapies in treating idiopathic, actinic, and metabolically induced skin hyperpigmentation. A thorough review of the literature regarding oral treatments for hyperpigmentation was systematically conducted through PubMed. Keywords used in the primary search include “Hyperpigmentation,” “Melanosis” or “Melasma,” “Lightening,” “Oral,” and “Therapeutics.” The search was limited to the English language, and no timeframe restrictions were implemented. Numerous orally administered therapies have been proposed for the treatment of skin hyperpigmentation. There is an abundant body of literature demonstrating the efficacy of orally administered tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. It is reasonable to expect that the most effective oral therapies will address known underlying causes of hyperpigmentation such as thyroid disease, diabetes, and hormonal imbalance. Improvement due to oral therapy of otherwise unresponsive skin hyperpigmentation or hyperpigmentation of unknown cause is less predictable. This review is limited by the strength of evidence contained within the available studies. Clinical studies investigating the treatments discussed within this article are limited in number, at times lack blinding in the study design, and are based on small sample sizes. Based on existing research, the most promising oral remedies for hyperpigmentation appear to be tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. Additional studies to better establish safety and efficacy are necessary.

Research ObjectiveAn artificial intelligence (AI) algorithm based on ECG was integrated into clinical workflows to identify patients with a high likelihood of low ejection (EF), a condition that is underdiagnosed but treatable. The trial aimed to assess whether the AI‐powered clinical decision support enabled early diagnosis of low EF.Study DesignA pragmatic, cluster randomized controlled trial (RCT) was conducted in 45 primary care practices, including an academic medical center as well as community and rural clinics across Minnesota and Wisconsin. A total of 120 primary care teams, including 358 clinicians, were randomized to either intervention (access to AI results with positive results indicating a high likelihood of low EF; 181 clinicians) or control (usual care; 177 clinicians). The primary endpoint was a new diagnosis of EF≤50% within 90 days. A positive deviance qualitative study and a survey were used to assess implementation strategies.Population StudiedIn total, 22,641 adult patients (N = 11,573 intervention; N = 11,068 control) with ECG performed as part of routine care between 8/5/2019 and 3/31/2020 were included. Patients were excluded if they had known EF≤50% or a history of documented heart failure (HF) identified by clinical notes abstracted by natural language processing.Principal FindingsThe mean age of patients was 60.5 ± 17.6 years; 53.9% were women. Positive AI results were found in 6.0% of patients in both arms. Clinicians in the intervention group obtained more echocardiograms for patients with positive results (38.1% control vs. 49.6% intervention, p < 0.001), but in the overall cohort, the echocardiogram utilization was similar (18.2% vs. 19.2%, p = 0.17). The intervention increased the diagnosis of low EF in the overall cohort (1.6% vs. 2.1%, odds ratio [OR] 1.32 [1.01–1.61], p = 0.007) and among patients with positive results (14.5% vs. 19.5% OR 1.43 [1.08–1.91], p = 0.01). Results using different thresholds for low EF were consistent with the primary result. Among patients with positive results, the intervention increased echocardiography more significantly in women vs. men (p for interaction 0.02), in patients without prior echocardiogram vs. those with prior echocardiogram (p for interaction 0.04), and in patients whose ECGs were ordered in outpatient clinics (p for interaction 0.02).ConclusionsAn AI algorithm run on existing ECGs enabled the early diagnosis of low EF in a large cohort of patients managed in routine primary care practices. Because ECG is a low‐cost test frequently performed for a variety of purposes, the algorithm could improve early diagnosis and treatment of a condition that is often asymptomatic but has effective treatments, and thus, reduce the disease burden in broad populations.Implications for Policy or PracticeThe current study is one of the first RCTs that demonstrated the value of AI in routine practice. Low EF confers an increased risk of HF progression and mortality. Although there are effective therapies, low EF is undiagnosed, leading to missed opportunities for treatment. EF can be readily determined by echocardiography, but the imagining test is too resource‐intensive to screen unselected populations. The AI applied to the existing ECGs could identify high‐risk patients for further assessment.Primary Funding SourceMayo Clinic.

ABSTRACT Vacuoles, E1 enzyme, X linked, autoinflammatory, somatic (VEXAS) syndrome is a recently described X-linked autoinflammatory condition associated with somatic mutation of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. It often coexists with myelodysplastic syndrome, which can occur due to DNA (cytosine-5)-methyltransferase 3A (DNMT3A) mutation. These patients, predominantly males, present after the fifth decade of life with unique systemic inflammatory clinical features and have haematological abnormalities and vacuolated precursor cells on bone marrow pathology. Here we describe a unique case of VEXAS syndrome in a patient harbouring DNMT3A gene mutation with coexisting UBA1 mutation with a review of literature.

SummaryFedratinib, an oral Janus kinase‐2 (JAK2) inhibitor, reduces splenomegaly and improves symptom burden in patients with myelofibrosis. Regulatory approval of fedratinib 400‐mg daily was based on results of an updated analysis of the pivotal phase III, placebo‐controlled JAKARTA trial in patients with JAK‐inhibitor‐naïve myelofibrosis. At week 24, spleen volume response rate was 47% and symptom response rate was 40% with fedratinib 400 mg, versus 1% and 9% respectively, with placebo. Common adverse events were diarrhoea, nausea, anaemia, and vomiting. No Wernicke encephalopathy occurred in patients receiving fedratinib 400 mg/day. These updated data support use of first‐line fedratinib in patients with myelofibrosis.

Abstract Background Bamlanivimab and casirivimab-imdevimab are authorized for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk patients. We compared the outcomes of patients who received these therapies to identify factors associated with hospitalization and other clinical outcomes. Methods Adult patients who received monoclonal antibody from 19 November 2020 to 11 February 2021 were selected and divided into those who received bamlanivimab (n = 2747) and casirivimab-imdevimab (n = 849). The 28-day all-cause and COVID-19–related hospitalizations were compared between the groups. Results The population included 3596 patients; the median age was 62 years, and 50% were female. All had ≥1 medical comorbidity; 55% had multiple comorbidities. All-cause and COVID-19–related hospitalization rates at 28 days were 3.98% and 2.56%, respectively. After adjusting for medical comorbidities, there was no significant difference in all-cause and COVID-19–related hospitalization rates between bamlanivimab and casirivimab-imdevimab (adjusted hazard ratios [95% confidence interval], 1.4 [.9–2.2] and 1.6 [.8–2.7], respectively). Chronic kidney, respiratory and cardiovascular diseases, and immunocompromised status were associated with higher likelihood of hospitalization. Conclusions This observational study on the use of bamlanivimab and casirivimab-imdevimab in high-risk patients showed similarly low rates of hospitalization. The number and type of medical comorbidities are associated with hospitalizations after monoclonal antibody treatment.

AbstractEvidence for the human health effects of pesticides is needed to inform risk assessment. We studied the relationship between occupational insecticide use and risk of non‐Hodgkin lymphoma (NHL) by pooling data from nine case‐control studies participating in the InterLymph Consortium, including 7909 cases and 8644 controls from North America, the European Union and Australia. Insecticide use was coded using self‐report or expert assessment, for insecticide groups (eg, organophosphates, pyrethroids) and active ingredients (eg, malathion, permethrin). Associations with insecticides were estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CI) for all NHL and NHL subtypes, with adjustment for study site, demographic factors and use of other pesticides. Occupational insecticide use, overall, was not associated with risk of NHL. Use of organophosphate insecticides was associated with increased risk of all NHL and the subtype follicular lymphoma, and an association was found with diazinon, in particular (ever use: OR = 2.05, 95%CI: 1.24‐3.37). The carbamate insecticide, carbaryl, was associated with risk of all NHL, and the strongest associations were found with T‐cell NHL for ever‐use (OR = 2.44, 95%CI: 1.13‐5.28) and longer duration (>8 years vs never: OR = 2.90, 95%CI: 1.02‐8.25). There was no association of NHL with other broad groups of insecticides, including organochlorines and pyrethroids, and some inverse associations were estimated in relation to historical DDT use. Our findings contribute to the totality of evidence available to help inform risk decisions by public health and regulatory agencies of importance given continued, widespread use of organophosphate and carbamate insecticides.