Transforming diabetes care with continuous glucose monitoring: Rationale for expanded eligibility criteria.

ABSTRACT: Randomized trials and large retrospective database studies have shown that individuals treated with noninsulin therapies experience the same glycemic benefits from continuous glucose monitoring (CGM) use as those treated with more intensive treatment regimens. However, many policy makers and payers are reluctant to provide CGM coverage for these patients. Although the recent American Diabetes Association guidelines have taken an important first step in recommending that CGM should be offered to all adults treated with basal insulin who are capable of using it, clinicians should consider the acute and long-term consequences of persistent hyperglycemia in all of their patients with diabetes. This article describes how the use of the FreeStyle Libre 2 CGM System (Abbott Diabetes Care, Alameda, CA) improved glycemic outcomes and facilitates personalized diabetes care in two type 2 diabetes patients treated with noninsulin therapies.

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

Overview of screening eligibility in patients undergoing ruptured AAA repair from 2003 to 2019 in the Vascular Quality Initiative.

OBJECTIVE: Although efforts such as the Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act have improved access to abdominal aortic aneurysm (AAA) screening, certain high-risk populations are currently excluded from the guidelines yet may benefit from screening. We therefore examined all patients who underwent repair of ruptured AAA (rAAA) to characterize those who are ineligible for screening under current guidelines and evaluate the potential impact of these restrictions on their disease. METHODS: We identified patients undergoing rAAA repair in the Vascular Quality Initiative (VQI) database between 2003 and 2019. These patients were stratified by AAA screening eligibility according to the Centers for Medicare and Medicaid reimbursement guidelines. We then described baseline characteristics to identify high-risk features of these cohorts. Groups with disproportionate representation in the screening-ineligible cohort were identified as potential targets of screening expansion. Trends over time in screening eligibility and the proportion of AAA repairs performed for rAAA were also analyzed. RESULTS: A total of 5340 patients underwent rAAA repair. The majority (66%) were screening-ineligible. When characterizing the screening-ineligible group by sex and risk factors (smoking history or family history of AAA), the largest contributors to screening ineligibility were males less than 65 years of age with a smoking history or family history of AAA (25%), males greater than 75 years of age with a smoking history (25%), and females older than 65 years of age with a smoking history (19%). In comparison with rAAAs prior to implementation of the SAAAVE act, the proportion of AAA repair performed for rupture among males undergoing AAA repair in the VQI decreased from 12% to 8% (P < .001), whereas in females, there was no change (P = .990). There was no statically significant difference in screening eligibility for either males (P = .762) or females (P = .335). CONCLUSIONS: Most patients who underwent rAAA repair were ineligible for initial AAA screening or aged out of the screening window. Furthermore, rAAA rates and screening ineligibility have not improved as much as expected since the passage of the SAAAVE Act. Our data suggest that three high-risk populations may benefit from expansion of AAA screening guidelines: males with a smoking history or family history of AAA between ages 55 and 64 years, female smokers older than 65 years, and male smokers older than 75 years who are otherwise in good health. Increased efforts to screen these high-risk populations may increase elective AAA repair and minimize the morbidity and mortality associated with rAAAs.

Toward endovascular treatment of type A aortic dissection with smaller landing zones and more patient eligibility.

OBJECTIVE: Type A or ascending aortic dissection is an acute life-threatening condition with high morbidity and mortality. Open surgery remains the standard of care. The development of minimally invasive endografts for type A aortic dissection (TAAD) will require a detailed understanding of the dissection and aortic root anatomy to determine patient eligibility and optimal device specifications. METHODS: Computed tomography images of TAAD cases at our institution from 2012 to 2019 were identified, and three-dimensional reconstructions were performed using OsiriX, version 10.0 (Pixmeo SARL, Bernex, Switzerland). We analyzed key anatomic structures, including centerline length measurements, ascending aorta and aortic root dimensions, and the location and extent of dissection in relationship to the coronary ostia. RESULTS: A total of 53 patients were identified (mean ± standard deviation age, 60.4 ± 17.1 years; 36 men and 17 women), 46 of whom had undergone surgery for TAAD. Four patients had died within 30 days of surgery. In 47 patients (88.7%), the entry tear was distal to the highest coronary ostium. These cases were retrospectively considered for endovascular intervention using a nonbranched, single endograft stent. The proximal landing zone (LZ) was defined as the distance from the highest coronary ostium to the entry tear. Of the 53 patients, 35 (66.0%) had a proximal LZ length of ≥2.0 cm, 38 (71.7%) had a proximal LZ length of ≥1.5 cm, and 42 (79.2%) had a proximal LZ length of ≥1.0 cm. The median proximal and distal LZ diameters of the sinotubular junction (STJ) and distal ascending aorta regions were 3.29 cm (interquartile range [IQR], 2.73-4.10 cm) and 3.49 cm (IQR, 3.09-3.87 cm, respectively), with a median length from the STJ to the innominate takeoff of 8.08 cm (IQR, 6.96-9.40 cm). The median ascending aorta radius of curvature was 6.48 cm (IQR, 5.27-8.00 cm). Of the 53 patients, 25 (47.2%) could be treated with a straight tube graft with a ≤20% diameter mismatch between the proximal and distal LZs. CONCLUSIONS: Almost 80% of the patients with TAAD had had a proximal LZ of ≥1.0 cm. Of these patients, 47.2% had anatomy amenable for endovascular therapy with a nontapered straight tube graft using commercially available devices. To increase patient eligibility for TAAD endovascular intervention, enhanced precision deployment with an adequate seal in shorter LZs will be required. Our results can serve as a guide for endovascular device specifications designed to treat this devastating condition.

Eligibility for cervical cancer screening exit: Comparison of a national and safety net cohort.

OBJECTIVE: To determine eligibility for discontinuation of cervical cancer screening. METHODS: Women aged 64 with employer-sponsored insurance enrolled in a national database between 2016 and 2018, and those aged 64-66 receiving primary care at a safety net health center in 2019 were included. Patients were evaluated for screening exit eligibility by current guidelines: no evidence of cervical cancer or HIV-positive status and no evidence of cervical precancer in the past 25 years, and had evidence of either hysterectomy with removal of the cervix or evidence of fulfilling screening exit criteria, defined as two HPV screening tests or HPV plus Pap co-tests or three Pap tests within the past 10 years without evidence of an abnormal result. RESULTS: Of the 590,901 women in the national claims database, 131,059 (22.2%) were eligible to exit due to hysterectomy (1.6%) or negative screening (20.6%). Of the 1544 women from the safety net health center, 528 (34.2%) were eligible to exit due to hysterectomy (9.3%) or negative screening (24.9%). Most women did not have sufficient data available to fulfill exit criteria: 382,509 (64.7%) in the national database and 875 (56.7%) in the safety net hospital system. Even among women with 10 years of insurance claims data, only 41.5% qualified to discontinue screening. CONCLUSIONS: Examining insurance claims in a national database and electronic medical records at a safety net institution led to remarkably similar findings: two thirds of women fail to qualify for screening exit. Additional steps to ensure eligibility prior to screening exit may be necessary to decrease preventable cervical cancers among women aged >65. CLINICAL TRIAL REGISTRATION: N/A.

Association of the Comprehensive Care for Joint Replacement Model With Disparities in the Use of Total Hip and Total Knee Replacement.

Importance: The Comprehensive Care for Joint Replacement (CJR) model is Medicare's mandatory bundled payment reform to improve quality and spending for beneficiaries who need total hip replacement (THR) or total knee replacement (TKR), yet it does not account for sociodemographic risk factors such as race/ethnicity and income. Results of this study could be the basis for a Medicare payment reform that addresses inequities in joint replacement care. Objective: To examine the association of the CJR model with racial/ethnic and socioeconomic disparities in the use of elective THR and TKR among older Medicare beneficiaries after accounting for the population of patients who were at risk or eligible for these surgical procedures. Design, Setting, and Participants: This cohort study used the 2013 to 2017 national Medicare data and multivariable logistic regressions with triple-differences estimation. Medicare beneficiaries who were aged 65 to 99 years, entitled to Medicare, alive at the end of the calendar year, and residing either in the 67 metropolitan statistical areas (MSAs) mandated to participate in the CJR model or in the 104 control MSAs were identified. A subset of Medicare beneficiaries with a diagnosis of arthritis underwent THR or TKR. Data were analyzed from March to December 2020. Exposures: Implementation of the CJR model in 2016. Main Outcomes and Measures: Outcomes were separate binary indicators for whether a beneficiary underwent THR or TKR. Key independent variables were MSA treatment status, pre- or post-CJR model implementation phase, combination of race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic beneficiaries) and dual eligibility, and their interactions. Logistic regression models were used to control for patient characteristics, MSA fixed effects, and time trends. Results: The 2013 cohort included 4 447 205 Medicare beneficiaries, of which 2 025 357 (45.5%) resided in MSAs with the CJR model. The cohort's mean (SD) age was 77.18 (7.95) years, and it was composed of 2 951 140 female (66.4%), 3 928 432 non-Hispanic White (88.3%), and 657 073 dually eligible (14.8%) beneficiaries. Before the CJR model implementation, rates were highest among non-Hispanic White non-dual-eligible beneficiaries at 1.25% (95% CI, 1.24%-1.26%) for THR use and 2.28% (95% CI, 2.26%-2.29%) for TKR use in MSAs with CJR model. Compared with MSAs without the CJR model and the analogous race/ethnicity and dual-eligibility group, the CJR model was associated with a 0.10 (95% CI, 0.05-0.15; P < .001) percentage-point increase in TKR use for non-Hispanic White non-dual-eligible beneficiaries, a 0.11 (95% CI, 0.004-0.21; P = .04) percentage-point increase for non-Hispanic White dual-eligible beneficiaries, a 0.15 (95% CI, -0.29 to -0.01; P = .04) percentage-point decrease for non-Hispanic Black non-dual-eligible beneficiaries, and a 0.18 (95% CI, -0.34 to -0.01; P = .03) percentage-point decrease for non-Hispanic Black dual-eligible beneficiaries. These CJR model-associated changes in TKR use were 0.25 (95% CI, -0.40 to -0.10; P = .001) percentage points lower for non-Hispanic Black non-dual-eligible beneficiaries and 0.27 (95% CI, -0.45 to -0.10; P = .002) percentage points lower for non-Hispanic Black dual-eligible beneficiaries compared with the model-associated changes for non-Hispanic White non-dual-eligible beneficiaries. No association was found between the CJR model and a widening of the THR use gap among race/ethnicity and dual eligibility groups. Conclusions and Relevance: Results of this study indicate that the CJR model was associated with a modest increase in the already substantial difference in TKR use among non-Hispanic Black vs non-Hispanic White beneficiaries; no difference was found for THR. These findings support the widespread concern that payment reform has the potential to exacerbate disparities in access to joint replacement care.

Eligibility for clinical trials is unsatisfactory for patients with myelodysplastic syndromes, even at a tertiary referral center.

Participation in clinical trials may allow patients with MDS to gain access to therapies not otherwise available. However, access is limited by strict inclusion and exclusion criteria, reflecting academic or regulatory questions addressed by the respective studies. We performed a simulation in order to estimate the average proportion of MDS patients eligible for participation in a clinical trial. The simulation drew upon 1809 patients in the Düsseldorf MDS Registry whose clinical data allowed eligibility screening for a wide range of clinical trials. This cohort was assumed to be alive and available for study participation. The simulation also posited that all MDS trials (n = 47) conducted in our center between 1987 and 2016 were open for recruitment. In addition, study activities in the year 2016 were analyzed to determine the proportion of patients eligible for at least one of the 9 MDS trials open at that time. On average, each clinical trial was suitable for about 18 % of patients in the simulation cohort. Conversely, 34 % of the patients were eligible for at least one of the 9 clinical studies in 2016. Inclusion/exclusion criteria of studies initiated by the pharmaceutical industry excluded more than twice the fraction of patients compared with investigator initiated trials (potential inclusion of 10 % vs. 21 %, respectively). Karyotype (average exclusion rate 58 %), comorbidities (40 %), and prior therapies (55 %) were the main reasons for exclusion. We suggest that in- and exclusion criteria should be less restrictive, in order to meet the needs of the real-life population of elderly MDS patients.

Severe asthma and eligibility for biologics in a Brazilian cohort.

OBJECTIVE: This study aims to describe the eligibility for biologic therapies for severe asthma (SA) in a cohort of patients attending the Program for Control of Asthma (ProAR) in Bahia, Brazil. METHODS: Data from SA patients (≥18 years old) attending the ProAR, that were included in a case-control study conducted from 2013 to 2015, were used to reassess patients according to a modified ERS/ATS 2014 SA criteria. Patients were then classified according to the eligibility for SA biological therapy based on current prescription labels. RESULTS: From 544 patients in the cohort, 531 (97.6%) were included and 172 (32.4%) were identified as SA patients according to the ERS/ATS 2014 modified criteria. Of these 172 patients, 69 (40.1%) were ineligible for any of the biologicals approved for asthma (omalizumab, mepolizumab, reslizumab and benralizumab), 60 (34.9%) patients were eligible for one of the biological therapies, and 10 (5.8%) patients were eligible for all biological therapies. CONCLUSIONS: More than half of patients with SA were eligible for biologic therapy in our study, but none of them received this form of treatment. Almost half of them were not eligible to any of the approved biologics, however. The variability and overlap in patients' eligibility highlight the importance of evaluating each patient individually for a more personalized treatment approach. While there is a need to increase access for some of those eligible that may really need a biologic treatment, continuous efforts are required to develop alternatives to those who are not eligible.

Quality improvement for reducing utilization drift in hypoxic-ischemic encephalopathy management.

OBJECTIVES: Therapeutic hypothermia is an effective neuroprotective intervention for infants with moderate or severe hypoxic-ischemic encephalopathy (HIE). With the introduction of new medical therapy comes a learning curve with regards to its proper implementation and understanding of eligibility guidelines. We hypothesized that variation in patient selection and lack of adherence to established protocols contributed to the utilization drift away from the original eligibility guidelines. METHODS: A retrospective cohort study was conducted including infants who received therapeutic hypothermia in the neonatal intensive care unit (NICU) for HIE to determine utilization drift. We then used QI methodology to address gaps in medical documentation that may lead to the conclusion that therapeutic hypothermia was inappropriately applied. RESULTS: We identified 54% of infants who received therapeutic hypothermia who did not meet the clinical, physiologic, and neurologic examination criteria for this intervention based on provider admission and discharge documentation within the electronic medical record (EMR). Review of the charts identified incomplete documentation in 71% of cases and led to the following interventions: 1) implementation of EMR smartphrases; 2) engagement of key stakeholders and education of faculty, residents, and neonatal nurse practitioners; and 3) performance measurement and sharing of data. We were able to improve both adherence to the therapeutic hypothermia guidelines and achieve 100% documentation of the modified Sarnat score. CONCLUSIONS: Incomplete documentation can lead to the assumption that therapeutic hypothermia was inappropriately applied when reviewing a patient's EMR. However, in actual clinical practice physicians follow the clinical guidelines but are not documenting their medical decision making completely. QI methodology addresses this gap in documentation, which will help determine the true utilization drift of therapeutic hypothermia in future studies.

Struggle for the Soul of Medicaid.

Medicaid is uniquely equipped to serve low-income populations. We identify four features that form the "soul" of Medicaid, explain how the administration is testing them, and explore challenges in accountability contributing to this struggle. We highlight the work of watchdogs acting to protect Medicaid and conclude with considerations for future health reform.

Gender as a principle of the organization of clinical sleep research.

In 2014 the National Institutes of Health required researchers to examine sex as a biological variable. While this approach is necessary to ensure adequate and appropriate female inclusion in research studies, it puts researchers at high risk for attributing their findings to biological sex differences when instead they may be more appropriately attributed to the influence and expectations of gender. In this paper, we specify how gender works as a principle of the social organization of symptoms, experiences, research, and clinical practice using obstructive sleep apnea symptomology to illustrate these patterns. We draw from psychologist Sandra Bem's account differentiating three specific mechanisms of gender: gender polarization, androcentrism, and biological essentialism.

Comorbidity Assessment Is Uneven Across Veterans Health Administration and Medicare for the Same Patient: Implications for Risk Adjustment.

OBJECTIVE: Compare comorbidity identification in Medicare and Veterans Health Administration (VA) data for the purposes of risk adjustment. DATA SOURCES: Analysis of Medicare and VA datasets for dually-enrolled Veterans receiving care in both settings, fiscal years 2010-2014. STUDY DESIGN: A retrospective analysis of administrative data for a national sample of cancer decedents. DATA EXTRACTION METHODS: Comorbidities were evaluated using Elixhauser and Charlson coding algorithms. PRINCIPAL FINDINGS: Clinical comorbidities were more likely to be recorded in Medicare than in VA datasets. Of 42 comorbidities, 36 (86%) were recorded at a different frequency. For example, congestive heart failure was recorded for 22.0% of patients in Medicare data and for 11.3% of patients in VA data (P<0.001). CONCLUSION: There are large differences in comorbidity assessment across VA and Medicare administrative data for the same patient, posing challenges for risk adjustment.

Eligibility Criteria and Endpoints in Metastatic Renal Cell Carcinoma Trials.

OBJECTIVES: Treatments for metastatic renal cell carcinoma (mRCC) are often compared across trials, but trial eligibility criteria and endpoints differ. In an effort to better align trials, the Definition for the Assessment of Time to event Endpoints in CANcer trials (DATECAN) project published recommendations in 2015 to be used in mRCC clinical trial design. We analyzed mRCC trial criteria to determine if DATECAN's recommendations were followed. MATERIALS AND METHODS: We compared eligibility criteria across 29 phase 3 mRCC trials conducted between 2003 and 2019. We then evaluated endpoints used in 10 phase 3 trials activated between 2015 and 2019 to determine their compliance with DATECAN's recommendations. RESULTS: Among the 29 trials, performance status, renal function, and disease characteristics differed in terms of requirements and measures used. In terms of endpoints, the 10 trials did not entirely follow DATECAN's recommendations. In total, 7/10 trials' primary endpoint was progression-free survival (PFS) as recommended; 4/9 trials used PFS as an endpoint but did not publish their definition of PFS, and the 5 that did, included "death from any cause" instead of DATECAN's recommendation of "death from kidney cancer." CONCLUSIONS: Key eligibility criteria were somewhat inconsistent across the phase 3 mRCC trials studied. Endpoints in the newer trials did not align with DATECAN's recommendations. Not only is greater standardization needed to facilitate meta-analyses and cross-trial comparisons, but as evident from lack of adherence to DATECAN's recommendations, greater promotion and adoption of recommendations are needed to better harmonize trial design.

Exclusion of Pregnant Women from Clinical Trials during the Coronavirus Disease 2019 Pandemic: A Review of International Registries.

OBJECTIVE: Pregnant women have been historically excluded from clinical trials for nonobstetric conditions, even during prior epidemics. The objective of this review is to describe the current state of research for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: We conducted a search of international trial registries for trials relating to the novel coronavirus. The eligibility criteria for each trial were reviewed for inclusion/exclusion of pregnant women. Relevant data were extracted and descriptive statistics were calculated for individual and combined data. The total number of trials from each registry were compared, as well as the proportions of pregnancy-related trials within each. RESULTS: Among 621,370 trials in the World Health Organization International Clinical Trials Registry, 927 (0.15%) were COVID-19 related. Of those, the majority (52%) explicitly excluded pregnancy or failed to address pregnancy at all (46%) and only 16 (1.7%) were pregnancy specific. When categorized by region, 688 (74.2%) of COVID-19 trials were in Asia, followed by 128 (13.8%) in Europe, and 66 (7.2%) in North America. Of the COVID-19 trials which included pregnant women, only three were randomized-controlled drug trials. CONCLUSION: Approximately 1.7% of current COVID-19 research is pregnancy related and the majority of trials either explicitly exclude or fail to address pregnancy. Only three interventional trials worldwide involved pregnant women. The knowledge gap concerning the safety and efficacy of interventions for COVID-19 created by the exclusion of pregnant women may ultimately harm them. While "ethical" concerns about fetal exposure are often cited, it is in fact unethical to habitually exclude pregnant women from research. KEY POINTS: · Pregnancy was excluded from past pandemic research.. · Pregnancy is being excluded from COVID-19 research.. · Exclusion of pregnant women is potentially harmful..

Expanding Access to Lung Cancer Clinical Trials by Reducing the Use of Restrictive Exclusion Criteria: Perspectives of a Multistakeholder Working Group.

Low rates of adult patient participation have been a persistent problem in cancer clinical trials and have continued to be a barrier to efficient drug development. The routine use of significant exclusion criteria has contributed to this problem by limiting participation in studies and creating significant clinical differences between the study cohorts and the real-world cancer patient populations. These routine exclusions also unnecessarily restrict opportunities for many patients to access potentially promising new therapies during clinical development. Multiple efforts are underway to broaden eligibility criteria, allowing more patients to enroll in studies and generating more robust data regarding the effect of novel therapies in the population at large. Focusing specifically on lung cancer as an example, a multistakeholder working group empaneled by the LUNGevity Foundation identified 14 restrictive and potentially outdated exclusion criteria that appear frequently in lung cancer clinical trials. As a part of the project, the group evaluated data from multiple recent lung cancer studies to ascertain the extent to which these 14 criteria appeared in study protocols and played a role in excluding patients (screen failures). The present report describes the working group's efforts to limit the use of these routine exclusions and presents clinical justifications for reducing the use of 14 criteria as routine exclusions in lung cancer studies, potentially expanding trial eligibility and improving the generalizability of the results from lung cancer trials.

Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement on Heart Transplantation: Patient Eligibility, Selection, and Post-Transplantation Care.

Significant practice-changing developments have occurred in the care of heart transplantation candidates and recipients over the past decade. This Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement provides evidence-based, expert panel recommendations with values and preferences, and practical tips on: (1) patient selection criteria; (2) selected patient populations; and (3) post transplantation surveillance. The recommendations were developed through systematic review of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The evolving areas of importance addressed include transplant recipient age, frailty assessment, pulmonary hypertension evaluation, cannabis use, combined heart and other solid organ transplantation, adult congenital heart disease, cardiac amyloidosis, high sensitization, and post-transplantation management of antibodies to human leukocyte antigen, rejection, cardiac allograft vasculopathy, and long-term noncardiac care. Attention is also given to Canadian-specific management strategies including the prioritization of highly sensitized transplant candidates (status 4S) and heart organ allocation algorithms. The focus topics in this position statement highlight the increased complexity of patients who undergo evaluation for heart transplantation as well as improved patient selection, and advances in post-transplantation management and surveillance that have led to better long-term outcomes for heart transplant recipients.