During geomagnetically disturbed conditions the midlatitude ionosphere is subject to intense poleward directed electric fields in the dusk‐midnight sector. These electric fields lead to the ...generation of a latitudinally narrow westward directed flow channel in the subauroral region called a subauroral polarization stream (SAPS). If the magnetic field lines are treated as equipotentials, electrodynamic events such as SAPS are expected to occur simultaneously at magnetically conjugate locations with similar features. In this paper we present simultaneous observations of a SAPS event in both hemispheres made by midlatitude SuperDARN radars with conjugate fields‐of‐view. We analyze the relation between the geomagnetic conditions and the characteristics of the channels such as latitudinal location, electric field, total potential variations across the channels, and Pedersen current. The results suggest a strong correlation between the strength of the ring current and the latitudinal location of the channel. An inter‐hemispheric comparison of the characteristics of the channel indicates that the potential variations across the channels are similar while the electric fields, Pedersen currents and latitudinal widths of the channel exhibit differences that are consistent with equal potential variations. We attribute these differences to seasonal differences in ionospheric conductivity between the hemispheres and magnetic distortion effects in the inner magnetosphere.
Key Points
Study the characteristics of SAPS observed in both hemispheres
Investigate the extent of inter‐hemispheric conjugacy exhibited during SAPS
Analyze the influence of geomagnetic conditions on SAPS
Older adults are characterized by profound clinical heterogeneity. When designing and delivering interventions, there exist multiple approaches to account for heterogeneity. We present the results of ...a systematic review of data‐driven, personalized interventions in older adults, which serves as a use case to distinguish the conceptual and methodologic differences between individualized intervention delivery and precision health‐derived interventions. We define individualized interventions as those where all participants received the same parent intervention, modified on a case‐by‐case basis and using an evidence‐based protocol, supplemented by clinical judgment as appropriate, while precision health‐derived interventions are those that tailor care to individuals whereby the strategy for how to tailor care was determined through data‐driven, precision health analytics. We discuss how their integration may offer new opportunities for analytics‐based geriatric medicine that accommodates individual heterogeneity but allows for more flexible and resource‐efficient population‐level scaling.
Using delivery system innovations to advance health care reform continues to be of widespread interest. However, it is difficult to generalize about the success of specific types of innovations, ...since they have been examined in only a few studies. To gain a broader perspective, we analyzed the results of forty-three ambulatory care programs funded by the first round of the Center for Medicare and Medicaid Innovation's Health Care Innovations Awards. The innovations' impacts on total cost of care were estimated by independent evaluators using multivariable difference-in-differences models. Through the first two years, most of the innovations did not show a significant effect on total cost of care. Using meta-regression, we assessed the effects on costs of five common components of these innovations. Innovations that used health information technology or community health workers achieved the greatest cost savings. Savings were also relatively large in programs that targeted clinically fragile patients-clinically complex populations at risk for disease progression. While the magnitude of these effects was often substantial, none achieved conventional levels of significance in our analyses. Meta-analyses of a larger number of delivery system innovations are needed to more clearly establish their potential for patient care cost savings.
Chronic limb‐threatening ischemia (CLTI) is associated with significant morbidity, including major limb amputation, and mortality. Healing ischemic wounds is necessary to optimise vascular outcomes ...and can be facilitated by dedicated appointments at a wound clinic. This study aimed to estimate the association between successful wound care initiation and 6‐month wound healing, with specific attention to differences by race/ethnicity. This retrospective study included 398 patients with CLTI and at least one ischaemic wound who scheduled an appointment at our wound clinic between January 2015 and July 2020. The exposure was the completion status of patients' first scheduled wound care appointment (complete/not complete) and the primary outcome was 6‐month wound healing (healed/not healed). The analysis focused on how this association was modified by race/ethnicity. We used Aalen–Johansen estimators to produce cumulative incidence curves and calculated risk ratios within strata of race/ethnicity. The final adjustment set included age, revascularization, and initial wound size. Patients had a mean age of 67 ± 14 years, were 41% female, 46% non‐White and had 517 total wounds. In the overall cohort, 70% of patients completed their first visit and 34% of wounds healed within 6‐months. There was no significant difference in 6‐month healing based on first visit completion status for White/non‐Hispanic individuals (RR 95% CI = 1.18 0.91, 1.45; p‐value = 0.130), while non‐White individuals were roughly 3 times more likely to heal their wounds if they completed their first appointment (RR 95% CI = 2.89 2.66, 3.11; p‐value < 0.001). In conclusion, non‐White patients were approximately three times more likely to heal their wound in 6 months if they completed their first scheduled wound care appointment while White/non‐Hispanic individuals' risk of healing was similar regardless of first visit completion status. Future efforts should focus on providing additional resources to ensure minority groups with wounds have the support they need to access and successfully initiate wound care.
Weak evidence, when manifested in clinical guidelines, can translate into biased vascular care. In vascular surgery, we have few randomized controlled trials with appropriate representation of ...females and persons of color, so generalizability of trial results can be problematic. Physicians are required to balance evidenced-based care (which is only as good as the underlying evidence) with personalized treatment recommendations that are often based on demographics, social circumstances, and/or existing therapeutic relationships. Biases, whether implicit or explicit, have an oversized effect on treatment decisions, and patient outcomes. In this commentary, we propose three principles to strengthen the vascular surgery evidence foundation and patient-centered decision-making going forward: (1) generating evidence designed for individualized care, (2) constructing clinical guidelines that are context specific and complexity aware, and (3) strengthening the training and support for surgeons to deliver patient-centered individualized care.
Randomized controlled trials (RCTs) are widely considered to provide the highest-quality evidence for the comparative efficacy and safety of competing clinical strategies. The strength of using RCTs ...for causal inference is derived from random treatment assignment and prospective data collection. Randomization eliminates confounding at the time of treatment group assignment, achieving exchangeability of the baseline study groups, such that they are the same, on average, except for the study intervention. Prospective data collection helps ensure that eligibility assessment, treatment assignment, and the start of follow-up are aligned temporally. Temporal alignment prevents biases that are common in observational research (eg, immortal time bias). In ideal settings, the results of an RCT provide the average causal effect of the intervention on the selected outcomes in the study population. Although observational research can estimate similar causal effects, observational designs require more assumptions and more advanced analytic frameworks than an RCT designed to answer the same question. Emerging trial designs, also discussed here, seek to address certain limitations of traditional RCT designs. The purpose of this review was to provide a broad overview of the central concepts in RCT design, implementation, conduct, and data analysis.
To set therapeutic benchmarks, in 2009 the Society for Vascular Surgery defined objective performance goals (OPG) for treatment of patients with chronic limb threatening ischemia (CLTI) with either ...open surgical bypass or endovascular intervention. The goal of these OPGs are to set standards of care from a revascularization standpoint and to provide performance benchmarks for 1 year patency rates for new endovascular therapies. While OPGs are useful in this regard, a critical decision point in the treatment of patients with CLTI is determining when revascularization is necessary. There is little guidance in the comprehensive treatment of this patient population, especially in the nonoperative cohort. Guidelines are needed for the CLTI patient population as a whole and not just those revascularized, and our aim was to assess whether CLTI OPGs could be attained with nonoperative management alone.
Our cohort included patients with an incident diagnosis of CLTI (by hemodynamic and symptomatic criteria) at our institution from 2013-2017. The primary outcome measured was mortality. Secondary outcomes were limb loss and failure of amputation-free survival. Descriptive statistics were used to define the 2 groups - patients undergoing primary revascularization and patients undergoing primary wound management. The risk difference in outcomes between the 2 groups was estimated using collaborative-targeted maximum likelihood estimation.
Our cohort included 349 incident CLTI patients; 60% male, 51% white, mean age 63 +/- 13 years, 20% Rutherford 4, and 80% Rutherford 5. Most patients (277, 79%) underwent primary revascularization, and 72 (21%) were treated with wound care alone. Demographics and presenting characteristics were similar between groups. Although the revascularized patients were more likely to have femoropopliteal disease (72% vs. 36%), both groups had a high rate of infrapopliteal disease (62% vs. 57%). Not surprisingly, the patients in the revascularization group were less likely to have congestive heart failure (34% vs. 42%), complicated diabetes (52% vs. 79%), obesity (19% vs. 33%), and end stage renal disease (14% vs. 28%). In the wound care group, 2-year outcomes were 65% survival, 51% amputation free survival, 19% major limb amputation, and 17% major adverse cardiac event. The wound care cohort had a 13% greater risk of death at 2 years; however, the risk of limb loss at 2 years was 12% less in the wound care cohort.
A comprehensive set treatment goals and expected amputation free survival outcomes can guide revascularization, but also assure that appropriate outcomes are achieved for patients treated without revascularization. The 2-year outcomes achieved in this cohort provide an estimate of outcomes for nonrevascularized CLTI patients. Although multi-center or prospective studies are needed, we demonstrate that equal, even improved, limb salvage rates are possible.
IntroductionSevere hypoglycemia (SH) in older adults (OAs) with type 1 diabetes is associated with profound morbidity and mortality, yet its etiology can be complex and multifactorial. Enhanced tools ...to identify OAs who are at high risk for SH are needed. This study used machine learning to identify characteristics that distinguish those with and without recent SH, selecting from a range of demographic and clinical, behavioral and lifestyle, and neurocognitive characteristics, along with continuous glucose monitoring (CGM) measures.Research design and methodsData from a case–control study involving OAs recruited from the T1D Exchange Clinical Network were analyzed. The random forest machine learning algorithm was used to elucidate the characteristics associated with case versus control status and their relative importance. Models with successively rich characteristic sets were examined to systematically incorporate each domain of possible risk characteristics.ResultsData from 191 OAs with type 1 diabetes (47.1% female, 92.1% non-Hispanic white) were analyzed. Across models, hypoglycemia unawareness was the top characteristic associated with SH history. For the model with the richest input data, the most important characteristics, in descending order, were hypoglycemia unawareness, hypoglycemia fear, coefficient of variation from CGM, % time blood glucose below 70 mg/dL, and trail making test B score.ConclusionsMachine learning may augment risk stratification for OAs by identifying key characteristics associated with SH. Prospective studies are needed to identify the predictive performance of these risk characteristics.
In the applied sciences, the ultimate goal is not just to acquire knowledge but to turn knowledge into action. The next wave for data disciplines may be experimental designs and analytical methods ...for closing the gap between the “real‐world” situations faced by decision‐makers and their idealized representations in optimization problems, and the health sciences are poised to be the discipline where these developments substantially improve lives. We discuss three recent trends in research—experimental designs and analytical methods for precision medicine and pragmatic trials; technological developments in sensors, wearables, and smartphones for measuring health data; and methods addressing algorithmic bias and model interpretability—and argue that these seemingly disparate trends point to a future where data‐driven decision support tools are increasingly used to promote wellbeing.
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulating T cell responses. A number of autoimmune diseases have shown genetic linkage to the CTLA-4 locus. We have ...cloned and expressed an alternatively spliced form of CTLA-4 that has genetic linkage with type I diabetes in the NOD mice. This splice variant of CTLA-4, named ligand-independent CTLA-4 (liCTLA-4), lacks exon2 including the MYPPPY motif essential for binding to the costimulatory ligands B7-1 and B7-2. Here we show that liCTLA-4 is expressed as a protein in primary T cells and strongly inhibits T cell responses by binding and dephosphorylating the TcRzeta chain. Expression of liCTLA-4, but not full-length CTLA-4 (flCTLA-4), was higher in memory/regulatory T cells from diabetes-resistant NOD congenic mice compared to susceptible NOD mice. These data suggest that increased expression and negative signaling delivered by the liCTLA-4 may regulate development of T cell-mediated autoimmune diseases.
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