Citations

A wireless, wearable Doppler ultrasound offers a new paradigm for linking physiology to resuscitation medicine. To this end, the image analysis of simultaneously-acquired venous and arterial Doppler spectrograms attained by wearable ultrasound represents a new source of hemodynamic data. Previous investigators have reported a direct relationship between the central venous pressure (CVP) and the ratio of the internal jugular-to-common carotid artery diameters. Because Doppler power is directly related to the number of red cell scatterers within a vessel, we hypothesized that (1) the ratio of internal jugular-to-carotid artery Doppler power (V/APOWER) would be a surrogate for the ratio of the vascular areas of these two vessels and (2) the V/APOWER would track the anticipated CVP change during simulated hemorrhage and resuscitation. To illustrate this proof-of-principle, we compared the change in V/APOWER obtained via a wireless, wearable Doppler ultrasound to B-mode ultrasound images during a head-down tilt. Additionally, we elucidated the change in the V/APOWER during simulated hemorrhage and transfusion via lower body negative pressure (LBNP) and release. With these Interesting Images, we show that the Doppler V/APOWER ratio qualitatively tracks anticipated changes in CVP (e.g., cardiac preload) which is promising for both diagnosis and management of hemodynamic unrest.

Objectives: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. Design and Methods: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. Results: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. Conclusion: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection.

Abstract Objectives We aimed to identify migraine treatment features preferred by patients and treatment outcomes most valued by patients. Background The values and preferences of people living with migraine are critical for both the choice of acute therapy and management approach of migraine. Methods We conducted a qualitative evidence synthesis. Two reviewers independently selected studies, appraised methodological quality, and undertook a framework synthesis. We developed summary of findings tables following the approach of Grading of Recommendations, Assessment, Development and Evaluations Confidence in the Evidence from Reviews of Qualitative Research to assess confidence in the findings. Results Of 1691 candidate references, we included 19 studies (21 publications) involving 459 patients. The studies mostly recruited White women from North America (11 studies) and Europe (8 studies). We identified eight themes encompassing features preferred by patients in a migraine treatment process. Themes described a treatment process that included shared decision‐making, a tailored approach, trust in health‐care professionals, sharing of knowledge and diversity of treatment options, a holistic approach that does not just address the headache, ease of communication especially for complex treatments, a non‐undermining approach, and reciprocity with mutual respect between patient and provider. In terms of the treatment itself, seven themes emerged including patients’ preferences for nonpharmacologic treatment, high effectiveness, rapidity of action, long‐lasting effect, lower cost and more accessibility, self‐management/self‐delivery option that increases autonomy, and a mixed preference for abortive versus prophylactic treatments. The treatment outcomes that have high value to patients included maintaining or improving function; avoiding side effects, potential for addiction to medications, and pain reoccurrence; and avoiding non‐headache symptoms such as nausea, vomiting, and sensitivity to light or sounds. Conclusion Patient values and preferences were individually constructed, varied widely, and could be at odds with conventional medical perspectives and evidence of treatment effects. Considering the availability of numerous treatments for acute migraine, it is necessary that decision‐making incorporates patient values and preferences identified in qualitative research. The findings of this qualitative synthesis can be used to facilitate an individually tailored approach, strengthen the patient–health‐care system relationship, and guide choices and decisions in the context of a clinical encounter or a clinical practice guideline.

AbstractContextHypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality.ObjectiveTo support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults.MethodsWe searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence.ResultsWe reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low.ConclusionThe evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients’ values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.

Abstract Context Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. Objective To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. Methods We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. Results We included 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels &lt;54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. Conclusion This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.

ImportanceProstate cancer (PCa) is marked by disparities in clinical outcomes by race, ethnicity, and age. Equitable enrollment in clinical trials is fundamental to promoting health equity.ObjectiveTo evaluate disparities in the inclusion of racial and ethnic minority groups and older adults across PCa clinical trials.Data SourcesMEDLINE, Embase, and ClinicalTrials.gov were searched to identify primary trial reports from each database's inception through February 2021. Global incidence in age subgroups and US population-based incidence in racial and ethnic subgroups were acquired from the Global Burden of Disease and Surveillance, Epidemiology, and End Results 21 incidence databases respectively.Study SelectionAll phase 2/3 randomized PCa clinical trials were eligible for age disparity analyses. Trials recruiting exclusively from the US were eligible for primary racial and ethnic disparity analyses.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were pooled using a random-effects model.Main Outcomes and MeasuresEnrollment incidence ratios (EIRs), trial proportions (TPs) of participants 65 years or older or members of a racial and ethnic subgroup divided by global incidence in the corresponding age group, or US population–based incidence in the corresponding racial and ethnic subgroup, were calculated. Meta-regression was used to explore associations between trial characteristics and EIRs and trends in EIRs during the past 3 decades.ResultsOf 9552 participants among trials reporting race, 954 (10.8%) were African American/Black, 80 (1.5%) were Asian/Pacific Islander, and 8518 (78.5) were White. Of 65 US trials, 45 (69.2%) reported race and only 9 (13.8%) reported data on all 5 US racial categories. Of 286 global trials, 75 (26.2%) reported the enrollment proportion of older adults. Outcomes by race and age were reported in 2 (3.1%) and 41 (15.0%) trials, respectively. Black (EIR, 0.70; 95% CI, 0.59-0.83) and Hispanic (EIR, 0.70; 95% CI, 0.59-0.83) patients were significantly underrepresented in US trials. There was no disparity in older adult representation (TP, 21 143 [71.1%]; EIR, 1.00; 95% CI, 0.95-1.05). The representation of Black patients was lower in larger trials (meta-regression coefficient, −0.06; 95% CI, −0.10 to −0.02; P = .002).Conclusions and RelevanceThe results of this meta-analysis suggest that Black and Hispanic men are underrepresented in trials compared with their share of PCa incidence. The representation of Black patients has consistently remained low during the past 2 decades.

Background To standardize renal functional magnetic resonance imaging (MRI), it is important to understand the influence of side‐to‐side variation, regional variation within the organ, and hydration states in MRI and to search for variables that are not affected by those variations. Purpose To assess MRI‐based biomarkers for characterizing the kidney in healthy volunteers while considering variations in anatomic factors and hydration states. Study Type Prospective. Subjects Twenty‐five healthy volunteers (15 females and 10 males, median age 25 years). Field Strength/Sequence 3.0 T intravoxel incoherent motion diffusion‐weighted imaging, arterial spinning labeling imaging, blood oxygenation level dependent imaging, and three‐dimensional MR elastography. Assessment Functional variables were measured before and after water challenge. Regions of interest were manually drawn by two investigators (JC and ZZ, with 8‐ and 5‐year experiences in abdominal radiology) in the cortex, the medulla, and the entire kidney. The medulla/cortex ratio was calculated. Statistical Tests Paired t ‐test or Wilcoxon signed rank test; interobserver correlation coefficient; repeatability coefficients; Spearman's correlation; significance level: P < 0.05. Results Diffusion parameters were only subject to regional variation. R2*, RBF, and renal stiffness (RS) showed regional variation, side variation, and dependence on hydration states. For each side and hydration state, the cortex showed significantly higher standard apparent diffusion coefficient (sADC), higher true diffusion ( D ), lower R2*, and lower RS than the medulla. For each region at baseline, the left kidney showed significantly higher R2*, higher RS, and lower renal blood flow (RBF) than the right kidney. For each region and side, RS and RBF increased significantly while R2* decreased significantly after water intake. After introducing the intrinsic regional difference, significantly higher medulla/cortex ratio of RS remained after water intake except for RS@90 Hz in the right kidney. Data Conclusion Renal multiparametric MRI quantifications were affected by regional variation, side variation, and hydration states. Level of Evidence 2 Technical Efficacy Stage 1