The Cardiac Pulsed Wave Doppler Pattern of the Common Femoral Vein in Diagnosing the Likelihood of Severe Pulmonary Hypertension: Results from a Prospective Multicentric Study.

Background and Objectives: Pulmonary hypertension (PH) is a clinical condition with high mortality rates, particularly in patients over 65. Current guidelines recommend assessing the likelihood of pulmonary hypertension (LPH) using advanced echocardiography before proceeding to right heart catheterization. This study proposed using the common femoral vein (CFV), an accessible vein that reflects right atrial pressure, as an alternative method to assess the high likelihood of pulmonary hypertension (H-LPH). Materials and Methods: This prospective observational study included 175 emergency patients from three hospitals. Ultrasound assessed the pulsed wave Doppler (PW-Doppler) morphology of the CFV. This diagnostic yield for H-LPH was evaluated alongside traditional ultrasound parameters (right-to-left ventricular basal diameter ratio greater than 1 (RV > LV), septal flattening, right ventricular outflow acceleration time (RVOT) of less than 105 ms and/or mesosystolic notching, pulmonary artery diameter greater than the aortic root (AR) diameter or over 25 mm, early pulmonary regurgitation maximum velocity > 2.2 m/s; TAPSE/PASP less than 0.55, inferior vena cava (IVC) diameter over 21 mm with decreased inspiratory collapse, and right atrial (RA) area over 18 cm2). Results: The CFV's PW-Doppler cardiac pattern correlated strongly with H-LPH, showing a sensitivity (Sn) of 72% and a specificity (Sp) of 96%. RA dilation and TAPSE/PASP < 0.55 also played significant diagnostic roles. Conclusions: The CFV's PW-Doppler cardiac pattern is an effective indicator of H-LPH, allowing reliable exclusion of this condition when absent. This approach could simplify initial LPH evaluation in emergency settings or where echocardiographic resources are limited.

Evaluating the Utility of ctDNA in Detecting Residual Cancer and Predicting Recurrence in Patients with Serous Ovarian Cancer.

Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence. We assessed 48 women diagnosed with serous ovarian cancer (47 high-grade and 1 low-grade) for visible residual disease and for ctDNA. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. We sequenced DNA samples for 59 breast and ovarian cancer driver genes. The plasma sample was collected after surgery and before initiating chemotherapy. We compared survival in women with no residual disease, with and without a positive plasma ctDNA test. We found tumour-specific variants (TSVs) in cancer cells from 47 patients, and these variants were sought in ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Thirty-one patients (65.9%) had no visible residual disease; of these, 24 (77.4%) patients had detectable ctDNA. Of the patients with no visible residual disease, those patients with detectable ctDNA had higher mortality (20 of 27 died) than those without detectable ctDNA (3 of 7 died) (HR 2.32; 95% CI: 0.67-8.05), although this difference was not statistically significant (p = 0.18). ctDNA in post-surgical serum samples may predict the presence of microscopic residual disease and may be a predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings.

What Is Known about Breast Cancer in Young Women?

Breast cancer (BC) is the second leading cause of cancer-related death in women under the age of 40 years worldwide. In addition, the incidence of breast cancer in young women (BCYW) has been rising. Young women are not the focus of screening programs and BC in younger women tends to be diagnosed in more advanced stages. Such patients have worse clinical outcomes and treatment complications compared to older patients. BCYW has been associated with distinct tumour biology that confers a worse prognosis, including poor tumour differentiation, increased Ki-67 expression, and more hormone-receptor negative tumours compared to women >50 years of age. Pathogenic variants in cancer predisposition genes such as BRCA1/2 are more common in early-onset BC compared to late-onset BC. Despite all these differences, BCYW remains poorly understood with a gap in research regarding the risk factors, diagnosis, prognosis, and treatment. Age-specific clinical characteristics or outcomes data for young women are lacking, and most of the standard treatments used in this subpopulation currently are derived from older patients. More age-specific clinical data and treatment options are required. In this review, we discuss the epidemiology, clinicopathologic characteristics, outcomes, treatments, and special considerations of breast cancer in young women. We also underline future directions and highlight areas that require more attention in future studies.

Improving representativeness in trials: a call to action from the Global Cardiovascular Clinical Trialists Forum.

Participants enrolled in cardiovascular disease (CVD) randomized controlled trials are not often representative of the population living with the disease. Older adults, children, women, Black, Indigenous and People of Color, and people living in low- and middle-income countries are typically under-enrolled in trials relative to disease distribution. Treatment effect estimates of CVD therapies have been largely derived from trial evidence generated in White men without complex comorbidities, limiting the generalizability of evidence. This review highlights barriers and facilitators of trial enrollment, temporal trends, and the rationale for representativeness. It proposes strategies to increase representativeness in CVD trials, including trial designs that minimize the research burden on participants, inclusive recruitment practices and eligibility criteria, diversification of clinical trial leadership, and research capacity-building in under-represented regions. Implementation of such strategies could generate better and more generalizable evidence to reduce knowledge gaps and position the cardiovascular trial enterprise as a vehicle to counter existing healthcare inequalities.

Potential clinical utility of liquid biopsies in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. One of the main challenges in the management of OC is the late clinical presentation of disease that results in poor survival. Conventional tissue biopsy methods and serological biomarkers such as CA-125 have limited clinical applications. Liquid biopsy is a novel sampling method that analyzes distinctive tumour components released into the peripheral circulation, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), cell-free RNA (cfRNA), tumour-educated platelets (TEPs) and exosomes. Increasing evidence suggests that liquid biopsy could enhance the clinical management of OC by improving early diagnosis, predicting prognosis, detecting recurrence, and monitoring response to treatment. Capturing the unique tumour genetic landscape can also guide treatment decisions and the selection of appropriate targeted therapies. Key advantages of liquid biopsy include its non-invasive nature and feasibility, which allow for serial sampling and longitudinal monitoring of dynamic tumour changes over time. In this review, we outline the evidence for the clinical utility of each liquid biopsy component and review the advantages and current limitations of applying liquid biopsy in managing ovarian cancer. We also highlight future directions considering the current challenges and explore areas where more studies are warranted to elucidate its emerging clinical potential.

Surgical versus conservative management of tongue lacerations in the acute care setting: A systematic review of the literature.

Objective: The objective of this study was to determine whether suturing or conservative management of tongue lacerations results in differences in wound healing and functional outcome. The secondary aim was to identify whether antibiotics are required in the treatment of tongue lacerations. Methods: Studies published between December 1954 and August 2020 were extracted from MEDLINE via PubMed, Embase via OVID, CINAHL via EBSCO, Web of Science, and the Cochrane Library and evaluated for inclusion based on predetermined inclusion and exclusion criteria by two independent reviewers in accordance with PRISMA guidelines. Results: The search yielded a total of 16,111 articles, 124 of which were evaluated by full-text review, resulting in 11 articles included in this systematic review representing 142 unique cases of tongue lacerations. At least 26 lacerations (18.3%) included penetration of the muscle layer of the tongue, and 24 (16.9%) were classified as full-thickness lacerations. Thirty-five of the 142 tongue lacerations (24.6%) were sutured. The remaining lacerations underwent some form of conservative management. The majority of studies reported excellent healing of tongue lacerations regardless of the management method, with minimal scarring and excellent return to normal functional status. No cases of infection were reported. Conclusions: Current literature is inconsistent with regards to indications and guidelines for primary repair of tongue lacerations. The majority of tongue lacerations reported in the literature heal with excellent outcomes regardless of management method. Physician judgement along with patient and parental preference based on potential risks of the procedure should be used when deciding whether a tongue laceration requires primary repair. Tongue lacerations in otherwise healthy individuals are at very low risk of infection.

Systemic Therapy for Atopic Dermatitis in Older Adults and Adults With Comorbidities: A Scoping Review and International Eczema Council Survey.

BACKGROUND: Clinical trials of systemic therapies for atopic dermatitis (AD) often exclude patients based on age and comorbidities. OBJECTIVES: We conducted a scoping review of observational studies and survey of International Eczema Council (IEC) members on the treatment of AD in patients with liver disease, renal disease, viral hepatitis, HIV, or history of malignancy. METHODS: We searched MEDLINE via Ovid, Embase via Ovid, and Web of Science from inception to September 14, 2020. We mapped the available evidence on the use of cyclosporine, methotrexate, azathioprine, mycophenolate, systemic corticosteroids, and dupilumab for AD in older adults (≥65 years) and adults with the previously mentioned comorbidities. We surveyed IEC members on their preferred systemic medications for each patient population. RESULTS: We identified 25 studies on the use of systemic medications in special populations of adults with AD. Although IEC members preferred dupilumab as the first-line systemic agent across all special populations, many could not identify viable third-line systemic therapy options for some populations. CONCLUSIONS: Data on systemic therapy for AD for older adults and adults with comorbidities are limited. Although IEC members' access to systemic therapies differs geographically, expert opinion suggests that dupilumab is preferred for those patients.

Racial Differences in the Prognosis and Survival of Cutaneous Melanoma From 1990 to 2020 in North America: A Systematic Review and Meta-Analysis.

BACKGROUND: Factors influencing the difference in the diagnosis and treatment of melanoma in racial minority groups are well-described in the literature and include atypical presentations and socioeconomic factors that impede access to care. OBJECTIVE: To characterize the differences in melanoma survival outcomes between non-Hispanic white patients and ethnic minority patients in North America. METHODS: We conducted searches of Embase via Ovid and MEDLINE via Ovid of studies published from 1989 to August 5, 2020. We included observational studies in North America which reported crude or effect estimate data on patient survival with cutaneous melanoma stratified by race. RESULTS: Forty-four studies met our inclusion criteria and were included in this systematic review. Pooled analysis revealed that black patients were at a significantly increased risk for overall mortality (HR 1.42, 95% CI, 1.25-1.60), as well as for melanoma-specific mortality (HR 1.27, 95% CI, 1.03-1.56). Pooled analyses using a representative study for each database yielded similar trends. Other ethnic minorities were also more likely report lower melanoma-specific survival compared to non-Hispanic white patients. CONCLUSION: Our results support findings that melanoma patients of ethnic minorities, particularly black patients, experience worse health outcomes with regards to mortality. Overall survival and melanoma-specific survival are significantly decreased in black patients compared to non-Hispanic white patients. With the advent of more effective, contemporary treatments such as immunotherapy, our review identifies a gap in the literature investigating present-day or prospective data on melanoma outcomes, in order to characterize how current racial differences compare to findings from previous decades.

Global representation of heart failure clinical trial leaders, collaborators, and enrolled participants: a bibliometric review 2000-20.

AIMS: The geographic representation of investigators and participants in heart failure (HF) randomized controlled trials (RCTs) may not reflect the global distribution of disease. We assessed the geographic diversity of RCT leaders and explored associations with geographic representation of enrolled participants among impactful HF RCTs. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and CINAHL for HF RCTs published in journals with impact factor ≥ 10 between January 2000 and June 2020. We used the Jonckheere-Terpstra test to assess temporal trends and multivariable logistic regression models to explore associations between predictors and outcomes. There were 414 eligible RCTs. Only 80 of 828 trial leaders [9.7%; 95% confidence interval (CI): 7.8-11.8%] and 453 of 4656 collaborators (9.7%; 95% CI: 8.8-10.6%) were from outside Europe and North America, with no change in temporal trends and with greater disparities in large RCTs. The adjusted odds of trial leadership outside Europe and North America were lower with industry funding [adjusted odds ratio (aOR): 0.33; 95% CI: 0.15-0.75; P = 0.008]. Among 157 416 participants for whom geography was reported, only 14.5% (95% CI: 14.3-14.7%) were enrolled outside Europe and North America, but odds of enrolment were 10-fold greater with trial leadership outside Europe and North America (aOR: 10.0; 95% CI: 5.6-19.0; P < 0.001). CONCLUSION: Regions disproportionately burdened with HF are under-represented in HF trial leadership, collaboration, and enrolment. RCT leadership outside Europe and North America is independently associated with participant enrolment in under-represented regions. Increasing research capacity outside Europe and North America could enhance trial diversity and generalizability.

Factors Associated With Racial and Ethnic Diversity Among Heart Failure Trial Participants: A Systematic Bibliometric Review.

BACKGROUND: Heart failure has a disproportionate burden on patients who are Black, Indigenous, and people of color (BIPOC), but not much is known about representation of these groups in randomized controlled trials (RCTs). We explored temporal trends in and RCT factors associated with the reporting of race and ethnicity data and the enrollment of BIPOC in heart failure RCTs. METHODS: We searched MEDLINE, EMBASE, and CINAHL for heart failure RCTs published in journals with an impact factor ≥10 between January 1, 2000 and June 17, 2020. We used the Cochran-Armitage and Jonchkeere-Terpstra tests to examine temporal trends, and multivariable regression to assess the association between trial characteristics and outcomes. RESULTS: Of 414 RCTs meeting inclusion criteria, only 157 (37.9% [95% CI, 33.2%-2.8%]) reported race and ethnicity data. Among 158 200 participants in these 157 RCTs, 29 512 (18.7% [95% CI, 18.5%-18.9%]) were BIPOC. There was a temporal increase in reporting of race and ethnicity data (29.5% in 2000-2003 to 54.7% in 2016-2020, P<0.001) and in enrollment of BIPOC (14.4% in 2000-2003 to 22.2% in 2016-2020, P=0.038). Trial leadership by a woman was independently associated with twice the odds of reporting race and ethnicity data (odds ratio, 2.0 [95% CI, 1.1-3.8]; P=0.028) and an 8.4% increase (95% CI, 1.9%-15.0%; P=0.013) in BIPOC enrollment. CONCLUSIONS: A minority of heart failure RCTs reported race and ethnicity data, and among these, BIPOC were under-enrolled relative to disease distribution. Both reporting of race and ethnicity as well as enrollment of BIPOC increased between 2000 and 2020. After multivariable adjustment, trials led by women had greater odds of reporting race and ethnicity and enrolling BIPOC. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021237497.

Predictive models for cardiovascular and kidney outcomes in patients with type 2 diabetes: systematic review and meta-analyses.

OBJECTIVE: To inform a clinical practice guideline (BMJ Rapid Recommendations) considering sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for treatment of adults with type 2 diabetes, we summarised the available evidence regarding the performance of validated risk models on cardiovascular and kidney outcomes in these patients. METHODS: We systematically searched bibliographic databases in January 2020 to identify observational studies evaluating risk models for all-cause and cardiovascular mortality, heart failure (HF) hospitalisations, end-stage kidney disease (ESKD), myocardial infarction (MI) and ischaemic stroke in ambulatory adults with type 2 diabetes. Using a random effects model, we pooled discrimination measures for each model and outcome, separately, and descriptively summarised calibration plots, when available. We used the Prediction Model Risk of Bias Assessment Tool to assess risk of bias of each included study and the Grading of Recommendations, Assessment, Development, and Evaluation approach to evaluate our certainty in the evidence. RESULTS: Of 22 589 publications identified, 15 observational studies reporting on seven risk models proved eligible. Among the seven models with >1 validation cohort, the Risk Equations for Complications of Type 2 Diabetes (RECODe) had the best calibration in primary studies and the highest pooled discrimination measures for the following outcomes: all-cause mortality (C-statistics 0.75, 95% CI 0.70 to 0.80; high certainty), cardiovascular mortality (0.79, 95% CI 0.75 to 0.84; low certainty), ESKD (0.73, 95% CI 0.52 to 0.94; low certainty), MI (0.72, 95% CI 0.69 to 0.74; moderate certainty) and stroke (0.71, 95% CI 0.68 to 0.74; moderate certainty). This model does not, however, predict risk of HF hospitalisations. CONCLUSION: Of available risk models, RECODe proved to have satisfactory calibration in primary validation studies and acceptable discrimination superior to other models, though with high risk of bias in most primary studies. TRIAL REGISTRATION NUMBER: CRD42020168351.

Association Between Topical Calcineurin Inhibitor Use and Risk of Cancer, Including Lymphoma, Keratinocyte Carcinoma, and Melanoma: A Systematic Review and Meta-analysis.

Importance: Topical calcineurin inhibitors (TCIs) are commonly used as second-line treatment for atopic dermatitis. In 2006, the US Food and Drug Administration issued a black box warning against TCI use, citing data from case reports and animal studies indicating a potential risk of cancer. Objective: To evaluate the association between TCI use and risk of malignant neoplasms compared with nonactive and active comparator groups. Data Sources: Electronic searches were conducted in MEDLINE via Ovid, Embase via Ovid, and Web of Science from database inception to August 21, 2020. Study Selection: Observational studies investigating the association between treatment with TCIs (ie, tacrolimus and pimecrolimus) and the development of cancer with nonactive or active comparators were included. The population of interest was not limited to any specific disease state, age, or sex. All articles were assessed independently and in duplicate by 2 reviewers. Risk of bias was assessed using the Newcastle-Ottawa scale. Of 2464 nonduplicate records retrieved from the search, 11 studies met the inclusion criteria. Data Extraction and Synthesis: Data extraction was conducted independently by 2 reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Random-effects meta-analyses were used to derive pooled relative risk (RR) estimates. Data were analyzed from July 25 to October 25, 2020. Main Outcomes and Measures: Risk of cancer overall and risk of specific cancer types (lymphoma, melanoma, and keratinocyte carcinoma). Results: Eight unique cohort studies (408 366 treated participants [55.1% female], 1 764 313 nonactive comparator controls, and 1 067 280 controls using topical corticosteroids) and 3 unique case-control studies (3898 cases [55.0% male] and 14 026 cancer-free controls [52.4% male]) were included. There was no association between TCI use and cancer overall compared with nonactive comparators (RR, 1.03; 95% CI, 0.92-1.16). Lymphoma risk was elevated with TCI use with both nonactive (RR, 1.86; 95% CI, 1.39-2.49) and topical corticosteroid comparators (RR, 1.35; 95% CI, 1.13-1.61). No significant association was found between TCI use and increased skin cancer (melanoma and keratinocyte carcinoma). Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest an association between TCI use and risk of lymphoma but not other cancers. Combined with the low absolute risk of lymphoma, the potential increased risk attributable to TCI use for any individual patient is likely very small.

Medically inoperable Merkel cell carcinoma of the head and neck treated with stereotactic body radiation therapy: a case report.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumour of the skin. MCC is the second most common cause of death from non-melanoma skin cancer and the most aggressive cutaneous malignancy. An 88-year-old male presented with a large, bleeding skin tumour located on the right temple and pre-auricular region. A biopsy confirmed MCC; immunohistochemistry (IHC) was positive for synaptophysin and CK20. The patient was assessed by a head and neck surgical oncologist and not deemed to have operable disease due to medical co-morbidities and extent of disease. The patient underwent a single fraction of electron treatment, followed by stereotactic body radiation therapy (SBRT) to a total dose of 40 Gy in 5 fractions over 2 weeks. Bleeding stopped and the patient tolerated treatment well with no reported side effects other than fatigue. There was symptomatic improvement within 2 weeks and a complete clinical response within 4 weeks of treatment. There are limited data on the use of radiotherapy in unresected/ inoperable MCC. For elderly, medically frail patients who cannot undergo surgery, SBRT may be an option to alleviate symptoms and control the tumour in a relatively short number of treatments; further study is warranted.

Diagnosis and Acute Management of E-Cigarette or Vaping Product Use-Associated Lung Injury in the Pediatric Population: A Systematic Review.

OBJECTIVE: To assess quantitative data on the presentation, investigative findings, patterns of lung injury, and interventions of pediatric cases of e-cigarette or vaping-associated lung injury (EVALI) in the acute care setting. STUDY DESIGN: A literature search using keywords was performed on April 17, 2020, in accordance with PRISMA guidelines. Three thousand five hundred fifty-eight articles were retrieved from MEDLINE via PubMed, Embase via OVID, CINAHL via EBSCO, Web of Science, and the Cochrane Library. Studies were evaluated for inclusion based on predetermined inclusion and exclusion criteria by 2 independent reviewers. RESULTS: The search yielded a total of 3558 individual results, 145 of which were evaluated by full text review, resulting in 23 articles included in this systematic review. Two of these articles were identified by manual search of article references. A total of 61 cases of EVALI were described, and 10 major patterns of lung injury were identified for which presenting symptoms, diagnostic and laboratory investigations, interventions, and outcomes were synthesized. CONCLUSIONS: Cases of EVALI in the pediatric population have been reported in patients as young as 13 years and often present with respiratory, constitutional, abdominal, and cardiovascular signs and symptoms. Diagnostic findings vary based on the underlying lung injury pattern. However, typical patterns of common findings were identified, including the presence of ground-glass opacities on computed tomography scan and leukocytosis. Mainstays of treatment include the use of corticosteroids, antibiotics, and ventilatory support, including extracorporeal membrane oxygenation. Outcomes range from complete or near complete recovery of lung function to death.

Diagnosis and Acute Management of Adolescent Cannabinoid Hyperemesis Syndrome: A Systematic Review.

PURPOSE: This study aimed to synthesize qualitative and quantitative data on the diagnosis and effective management of cannabinoid hyperemesis syndrome (CHS) in the adolescent population. METHODS: Using keywords, 1,334 studies published between December 1954 and December 2019 were extracted from MEDLINE via PubMed, Embase via OVID, CINAHL via EBSCO, Web of Science, and the Cochrane Library. Studies were evaluated by two independent reviewers using predetermined inclusion and exclusion criteria. RESULTS: The search yielded 148 studies for full-text review, of which 21 were included in this systematic review. A total of 10 articles were related to the diagnosis of CHS, while 11 articles discussed the treatment and management of adolescent cases of CHS. CONCLUSIONS: CHS in the adolescent population fulfills the major and minor diagnostic criteria of CHS in the adult population; however, in adolescent patients, CHS may present more frequently in females, with the earliest reported case presenting at age 15 years. There appears to be a substantial proportion (21%) of adolescent patients diagnosed with CHS that have a history of anxiety and depression; however, higher quality studies to assess the prevalence are warranted. Although haloperidol and topical capsaicin cream may provide symptom relief in isolated cases, complete cessation of cannabis use is currently the only known effective treatment.

Inclusion of Older Adults in Randomized Clinical Trials for Systemic Medications for Atopic Dermatitis: A Systematic Review.

Importance: Despite increasing evidence that atopic dermatitis is common in older adults, it is unclear whether the evidence base for treating atopic dermatitis with systemic therapy is generalizable to that population. Older adults are most at risk for adverse events from medications, given age-related alterations in drug metabolism, increased comorbidity, and polypharmacy. Objective: This systematic review examines the representation of older adults in randomized clinical trials (RCTs) of systemic immunomodulatory treatments for atopic dermatitis and whether safety and efficacy data are reported specifically for older individuals. Evidence Review: The Cochrane Central Register of Controlled Trials, Embase, MEDLINE databases, and the ClinicalTrials.gov trial register were searched from inception (MEDLINE via Ovid, 1946; Embase via Ovid, 1974) to November 7, 2019. RCTs investigating systemic immunomodulatory treatments for adults with atopic dermatitis were included. Titles, abstracts, and full-text papers were screened, and data were extracted in duplicate. Findings: A total of 32 trials with 4547 participants were reviewed. The mean (SD) age of trial participants was 34.4 (5.4) years. The median number of participants per trial was 44 (range, 10-740). Eleven trials (34%) reported explicit upper age limits ranging from 42 to 70 years of age. Most of these trials (n = 9) examined safety and effectiveness of cyclosporine. Twenty-two trials (69%) had other exclusion criteria that might disproportionately exclude older adults. In total, 10 trials (31%) included adults aged 65 years or older. Within 7 trials that reported the proportion of participants aged 65 and older (all evaluating dupilumab), 112 of 2964 participants (4%) were 65 years or older. None of the included trials reported stratified safety or effectiveness data for older adults. Conclusions and Relevance: Study results suggest that older adults are underrepresented in RCTs of systemic treatment for atopic dermatitis, resulting in a lack of evidence supporting safe clinical use for older adults. Clinicians and patients should be aware of this evidence gap when prescribing systemic therapy for atopic dermatitis. Randomized trials and observational studies that include older patients with atopic dermatitis are needed.