Local Social Vulnerability as a Predictor for Cancer-Related Mortality Among US Counties.

Substantial gaps in national healthcare spending and disparities in cancer mortality rates are noted across counties in the US. In this cross-sectional analysis, we investigated whether differences in local county-level social vulnerability impacts cancer-related mortality. We linked county-level age-adjusted mortality rates (AAMR) from the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research database, to county-level Social Vulnerability Index (SVI) from the CDC Agency for Toxic Substances and Disease Registry. SVI is a metric comprising 15 social factors including socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. AAMRs were compared between least and most vulnerable counties using robust linear regression models. There were 4 107 273 deaths with an overall AAMR of 173 per 100 000 individuals. Highest AAMRs were noted in older adults, men, non-Hispanic Black individuals, and rural and Southern counties. Highest mortality risk increases between least and most vulnerable counties were noted in Southern and rural counties, individuals aged 45-65, and lung and colorectal cancers, suggesting that these groups may face highest risk for health inequity. These findings inform ongoing deliberations in public health policy at the state and federal level and encourage increased investment into socially disadvantaged counties.

Outcomes with plug-based versus suture-based vascular closure device after transfemoral transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Studies comparing plug-based (i.e., MANTA) with suture-based (i.e., ProStar XL and ProGlide) vascular closure devices (VCDs) for large-bore access closure after transcatheter aortic valve replacement (TAVR) have yielded mixed results. AIMS: To examine the comparative safety and efficacy of both types of VCDs among TAVR recipients. METHODS: An electronic database search was performed through March 2022 for studies comparing access-site related vascular complications with plug-based versus suture-based VCDs for large-bore access site closure after transfemoral (TF) TAVR. RESULTS: Ten studies (2 randomized controlled trials [RCTs] and 8 observational studies) with 3113 patients (MANTA = 1358, ProGlide/ProStar XL = 1755) were included. There was no difference between plug-based and suture-based VCD in the incidence of access-site major vascular complications (3.1% vs. 3.3%, odds ratio [OR]: 0.89; 95% confidence interval [CI]: 0.52-1.53). The incidence of VCD failure was lower in plug-based VCD (5.2% vs. 7.1%, OR: 0.64; 95% CI: 0.44-0.91). There was a trend toward a higher incidence of unplanned vascular intervention in plug-based VCD (8.2% vs. 5.9%, OR: 1.35; 95% CI: 0.97-1.89). Length of stay was shorter with MANTA. Subgroup analyses suggested significant interaction based on study designs such that there was higher incidence of access-site vascular complications and bleeding events with plug-based versus suture-based VCD among RCTs. CONCLUSION: In patients undergoing TF-TAVR, large-bore access site closure with plug-based VCD was associated with a similar safety profile as suture-based VCD. However, subgroup analysis showed that plug-based VCD was associated with higher incidence of vascular and bleeding complications in RCTs.

Transcatheter edge-to-edge repair of the tricuspid valve: The US experience.

OBJECTIVES: To examine the trends in utilization and outcomes of tricuspid valve (TV) transcatheter edge-to-edge repair (TEER). BACKGROUND: Surgery for isolated tricuspid regurgitation is associated with high morbidity and mortality and is rarely performed. TV TEER is an attractive alternative. METHODS: The Nationwide Readmissions Database was queried using the International Classification of Diseases, 10th Revision, procedure code for TV TEER for years 2016-2019. The main outcomes were trends in utilization and in-hospital all-cause mortality. RESULTS: We identified 918 hospitalizations for TV TEER. There was an uptrend in its utilization from 13 cases in the first quarter of 2016 to 122 cases in the last quarter of 2019 (p trend < 0.001). Concomitant mitral valve (MV) TEER was performed in 42.1% of admissions. The overall in-hospital mortality was 2.1%. Surgical TV replacement was needed in 1.1% of admissions; none of them died during the index hospitalization. Unplanned rehospitalizations were common at 30 days (15.7%); 38.2% of those were due to heart failure. There was no difference in in-hospital mortality between isolated TV TEER and combined MV and TV TEER (1.7% vs. 2.6%, p = 0.359). However, admissions receiving combined procedure had lower length of stay and urgent readmission rate. CONCLUSION: The current study showed that there was an increase in the utilization of TV TEER over 2016-2019 in the United States. TV TEER was associated with low rates of in-hospital mortality; however, the rate of urgent readmission remains high, mainly due to heart failure.

The least costly pharmacy for cancer supportive care medications over time: the logistic toxicity of playing catch up.

PURPOSE: No single pharmacy in an urban zip code is consistently the least expensive across medications. If medication prices change differently across pharmacies, patients and clinicians will face challenges accessing affordable medications when refilling medications. This is especially pertinent to people with cancer with multiple fills of supportive care medications over time. We evaluated if the lowest-priced pharmacy for a formulation remains the lowest-priced over time. METHODS: We compiled generic medications used to manage nausea/vomiting (14 formulations) and anorexia/cachexia (12 formulations). We extracted discounted prices in October 2021 and again in March 2022 for a typical fill at 8 pharmacies in Minneapolis, Minnesota, USA (zip code 55,414) using GoodRx.com. We examined how prices changed across formulations and pharmacies over time. RESULTS: Data were available for all 208 possible pharmacy-formulation combinations (8 pharmacies × 26 formulations). For 172 (83%) of the 208 pharmacy-formulation combinations, the March 2022 price was within 20% of the October 2021 price. Across pharmacy-formulation combinations, the price change over time ranged from - 76 to + 292%. For 12 (46%) of the 26 formulations, at least one pharmacy with the lowest price in October 2021 no longer was the least costly in March 2022. For one formulation (dronabinol tablets), the least expensive pharmacy became the most expensive, with an absolute and relative price increase of a fill of $22 and 85%. CONCLUSION: For almost half of formulations studied, at least one pharmacy with the lowest price was no longer the least costly a few months later. The lowest price for a formulation (across pharmacies) could also change considerably. Thus, even if a patient accesses the least expensive pharmacy for a medication, they may need to re-check prices across all pharmacies with each subsequent fill to access the lowest prices. In addition to safety concerns, directing medications to and accessing medications at multiple pharmacies can add time and logistic toxicity to patients with cancer, their care partners, prescribers, and pharmacy teams.

Use of direct oral anticoagulants in chronic thromboembolic pulmonary hypertension: a systematic review.

Direct oral anticoagulants (DOACs) are being increasingly used in patients with chronic thromboembolic hypertension (CTEPH), however, the data on their safety and efficacy are scarce and contradictory. We systematically searched MEDLINE and Google Scholar databases from January 2010 to January 2021 for studies of DOACs in CTEPH. Three observational studies, 2 abstracts and one case series met our inclusion criteria. While these studies reported similar or even less rates of major bleeding in patients receiving DOACs compared with vitamin K antagonists, there were concerns about the possibility of increased risk of venous thromboembolism recurrence with DOAC therapy. Further studies are warranted to better define the role of DOACs in CTEPH.

Outcomes with catheter-directed thrombolysis compared with anticoagulation alone in patients with acute deep venous thrombosis.

OBJECTIVE: The authors aimed to investigate the benefits and risks of catheter-directed thrombolysis (CDT) in acute deep venous thrombosis (DVT). BACKGROUND: The role of CDT in the management of DVT is evolving. Data on CDT versus anticoagulation alone in acute DVT is sparse. METHODS: We performed a systematic review and meta-analysis of published studies that compared CDT to anticoagulation alone in patients with acute DVT. RESULTS: We included 11 studies (four randomized control trials [RCTs] and seven observational studies) with a total of 8,737 patients. During hospital stay, patients who received CDT had higher odds of major bleeding (2.5% vs. 1.6%; OR 1.46, 95% CI [1.07, 1.98], p = .02), blood transfusion (10.8% vs. 6.2%; OR 1.8, 95% CI [1.52, 2.13], p < .001), and thromboembolism (15.5% vs. 10%; OR 1.67, 95% CI [1.47, 1.91], p < .001) compared with anticoagulation alone. At 6-month follow-up, patients who received CDT had higher venous patency (71.1% vs. 37.7%; OR 5.49, 95% CI [2.63, 11.5], p < .001) and lower postthrombotic syndrome (PTS; 27% vs. 40.7%; OR 0.44, 95% CI [0.22, 0.86], p = .02). During a mean follow-up duration of 30.5 ± 28 months, CDT group continued to have higher venous patency (79.6% vs. 71.8%; OR 3.79, 95% CI [1.54, 9.32], p = .004) and lower PTS (44.7% vs. 50.5%; OR 0.43, 95% CI [0.23, 0.78], p = .006), but no difference in thromboembolism. CONCLUSION: Compared with anticoagulation alone, CDT for patients with acute DVT was associated with a higher risk of complications, but a higher rate of venous patency and lower risk of postthrombotic syndrome at 2.5 years follow-up.

End-of-Life Characteristics Associated With Short Hospice Length of Stay for Patients With Solid Tumors Enrolled in Phase I Clinical Trials.

BACKGROUND: Patients participating in phase I trials represent a population with advanced cancer and symptoms, with quality-of-life implications arising from both disease and treatment. Transitions to end-of-life care for these patients have received little attention. Good empirical data are needed to better understand the role of advance care planning and palliative care during phase I trial transitions. We investigated how physician-patient communication at the time of disease progression, patient characteristics, and patterns of care were associated with end-of-life care. METHODS: We conducted a retrospective chart review of all patients with solid tumors enrolled in phase I trials at a comprehensive cancer center from January 2015 to December 2017. We captured physician-patient communication during disease progression. Among patients who died, we assessed palliative care referral, advance care planning, place of death, healthcare use in the final month of life, hospice enrollment, and hospice length of stay (LOS). Factors independently associated with a short hospice LOS (defined as ≤3 days) were estimated from a multivariable model building approach. RESULTS: Among 207 participants enrolled in phase I intervention studies at Johns Hopkins Hospital, the median age was 61 years (range, 31-91 years), 48% were women, 21% were members of racial minority groups, and 41.5% were referred from an outside institution. At the time of disease progression, 53% had goals of care documented, 47% were previously referred to palliative care, and 41% discussed hospice with their oncologist. A total of 82% of decedents died within 1 year of study enrollment, and 85% enrolled in hospice. Among the 147 participants who enrolled in hospice, 22 (15%) had a short LOS (≤3 days). Factors independently associated with an increased risk of short hospice LOS in the multivariable model included age >65 years (odds ratio [OR], 1.12; 95% CI, 1.01-1.24; P=.04), whereas remaining at the same institution (OR, 0.72; 95% CI, 0.65-0.80; P<.001) and referral to palliative care before progression (OR, 0.83; 95% CI, 0.75-0.92; P<.001) were associated with a decreased risk of short hospice LOS. CONCLUSIONS: Reported data support the benefit of palliative care for patients in phase I trials and the risks associated with healthcare transitions for all patients, particularly older adults, regardless of care received. Leaving a clinical trial is a time when clear communication is paramount. Phase I studies will continue to be vital in advancing cancer treatment. It is equally important to advance the support provided to patients who transition off these trials.

How palliative care teams can mitigate financial toxicity in cancer care.

The disruption to patient and family well-being introduced by the rising costs of cancer care is a growing clinical problem. In addition to logistical questions, there is a compelling, existential one: "How should healthcare teams address patient and caregiver distress and uncertainty from financial toxicity?" We argue that the principles and practice of palliative care can help alleviate this element and often unaddressed component of human suffering.

Prostate Specific Antigen and Prostate Specific Antigen Doubling Time Predict Findings on 18F-DCFPyL Positron Emission Tomography/Computerized Tomography in Patients with Biochemically Recurrent Prostate Cancer.

PURPOSE: Prostate specific membrane antigen targeted 18F-DCFPyL positron emission tomography/computerized tomography may offer superior image quality and sensitivity for the detection of biochemically recurrent prostate cancer. We examined the association of Gleason sum, serum prostate specific antigen and prostate specific antigen doubling time with any detectable and pelvic confined disease in patients with biochemically recurrent prostate cancer. MATERIALS AND METHODS: Data from 108 patients with biochemically recurrent prostate cancer after radical prostatectomy who underwent prostate specific membrane antigen targeted 18F-DCFPyL positron emission tomography/computerized tomography were analyzed. Data were collected on positive positron emission tomography findings as well as pelvic confined disease. Associations between Gleason sum, prostate specific antigen and prostate specific antigen doubling time were retrospectively explored. RESULTS: Serum prostate specific antigen was associated with positive prostate specific membrane antigen targeted imaging as continuous (OR 3.08, 95% CI 1.60-7.95, p=0.005) and categorical values (ie prostate specific antigen greater than 2.0 to 5.0 vs 0.5 ng/ml or less, OR 16.92, 95% CI 3.13-315.81, p=0.008). No relationship between Gleason sum or prostate specific antigen doubling time with overall positive imaging was observed. Patients with a prostate specific antigen greater than 2.0 to 5.0 ng/ml were significantly less likely to be diagnosed with pelvic confined disease compared with the 0.5 ng/ml or less subgroup (OR 0.21, 95% CI 0.06-0.69, p=0.013). A prostate specific antigen doubling time of 9 months or more (OR 4.20, 95% CI 1.57-11.89, p=0.005) or prostate specific antigen doubling time of 12 months or more (OR 3.03, 95% CI 1.12-8.76, p=0.033) was significantly associated with pelvic confined disease. No relationship between Gleason sum and pelvic confined disease was observed. CONCLUSIONS: Absolute prostate specific antigen was positively associated with the presence of findings on prostate specific membrane antigen targeted imaging and negatively associated with pelvic confined disease. Prostate specific antigen doubling time did not predict for overall disease detection, but long prostate specific antigen doubling times were associated with pelvic confined prostate cancer.

Clinical implications of mismatch repair deficiency in prostate cancer.

Immune checkpoint blockade holds great promise in the treatment of solid tumors but has not yet been approved for use in advanced prostate cancer. This is largely due to the relatively modest response in clinical trials in unselected patients and the lack of available biomarkers to predict clinical benefit. Germline and somatic mismatch repair (MMR) gene deficiencies are more prevalent than previously thought, especially in the metastatic setting, in patients with high-grade Gleason scores and in patients with variant histologies. An early signal suggests that patients with deficiency in MMR may respond well to immunotherapy. Both germline and somatic genetic testing are recommended, yet questions remain on the best modality for testing given lack of standardization and false-negative results in patients with complex genomic structural rearrangements. Expanded panels, such as next generation sequencing may increase the sensitivity without compromising specificity. Future studies are still needed to explore the relationships of hypermutation, tumor mutational burden, tumor-infiltrating lymphocytes and microsatellite instability-H status as predictors of response to immunotherapy. The drivers of variable response is largely unknown, and a more mature understanding of the mechanisms of resistance in deficiencies in MMR tumors may help to more precisely inform use of immunotherapy in prostate cancer.

Mini-review of kidney disease following hematopoietic stem cell transplant
.

Advancements in hematopoietic cell transplantation (HCT) have broadened indications for its use and resulted in more long-term survivors. Stem cell transplantation is associated with several well-known toxicities, although renal complications are not well defined. Acute and chronic kidney disease remains a common complication following transplantation itself. Incidence and risk factors for the development of chronic kidney disease (CKD) is less well understood. Recent estimates suggest that nearly 15% of subjects undergoing HCT will develop CKD, a complication that can progress to end-stage renal disease (ESRD), disrupts overall quality of life, and reduces overall survival. Several commonly-reported risk factors include acute kidney injury, graft-versus-host disease, and long-term calcineurin inhibitor use. This review highlights the incidence, timeline, etiology, risk factors, and prognosis of kidney disease in the setting of hematopoietic stem cell transplantation. Investigation of the causes of CKD is needed, as are ways to prevent, mitigate, and treat kidney injury. Renal disease importantly reflects prognosis, with dialysis-requiring patients carrying greater than 80% mortality after 3 years. Although CKD following HCT is common, prospective studies are needed to confirm risk factors and better define the underlying mechanisms in order to promote therapies that prevent this complication.
.

Intracoronary adenosine compared with adrenaline and verapamil in the treatment of no-reflow phenomenon following primary PCI in STEMI patients.

BACKGROUND: no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). METHODS: 108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. RESULTS: The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. CONCLUSION: Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.

Outcomes With Malignancy-Associated High-Risk Pulmonary Embolism: A Nationwide Analysis.

OBJECTIVE: To examine the characteristics and outcomes among patients with high-risk pulmonary embolism (PE) and malignancy. PATIENTS AND METHODS: The Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2019. The main outcome was the difference in all-cause in-hospital mortality. RESULTS: Among 28,547 weighted hospitalizations with high-risk PE, 4,825 (16.9%) had malignancy. Admissions with malignancy had a lower prevalence of other comorbid conditions except for anemia and coagulopathy. The use of systemic thrombolysis, catheter-directed interventions, and surgical embolectomy was less common among admissions with malignancy, whereas the use of inferior vena cava filter was more common among those with malignancy. All-cause in-hospital mortality was higher among admissions with malignancy even after adjustment (adjusted odds ratio, 1.91; 95% CI, 1.72 to 2.11; P<.001). Metastatic genitourinary, gastrointestinal (other than colorectal), and lung malignancies were associated with the highest incidence of in-hospital mortality. The incidence of intracranial hemorrhage (3.9% vs 3.1%; P=.056) and the composite of non-intracranial hemorrhage bleeding (21.9% vs 20.6%; P=.185) was not different between admissions with and without malignancy. However, admissions with malignancy had higher incidence of gastrointestinal bleeding. CONCLUSION: In this nationwide analysis of patients admitted with high-risk PE, malignancy was independently associated with an increased risk of in-hospital mortality. The risk was highest among patients with metastatic genitourinary, gastrointestinal, and lung malignancies. Advanced therapies were less frequently used among patients with malignancy.

Global burden of cardiovascular disease attributable to smoking, 1990-2019: an analysis of the 2019 Global Burden of Disease Study.

AIMS: This study aims to investigate the trends in the global cardiovascular disease (CVD) burden attributable to smoking from 1990 to 2019. METHODS AND RESULTS: Global Burden of Disease Study 2019 was used to analyse the burden of CVD attributable to smoking (i.e. ischaemic heart disease, peripheral artery disease, stroke, atrial fibrillation and flutter, and aortic aneurysm). Age-standardized mortality rates (ASMRs) per 100 000 and age-standardized disability-adjusted life year rates (ASDRs) per 100 000, as well as an estimated annual percentage change (EAPC) in ASMR and ASDR, were determined by age, sex, year, socio-demographic index (SDI), regions, and countries or territories. The global ASMR of smoking-attributed CVD decreased from 57.16/100 000 [95% uncertainty interval (UI) 54.46-59.97] in 1990 to 33.03/100 000 (95% UI 30.43-35.51) in 2019 [EAPC -0.42 (95% UI -0.47 to -0.38)]. Similarly, the ASDR of smoking-attributed CVD decreased between 1990 and 2019. All CVD subcategories showed a decline in death burden between 1990 and 2019. The burden of smoking-attributed CVD was higher in men than in women. Significant geographic and regional variations existed such that Eastern Europe had the highest ASMR and Andean Latin America had the lowest ASMR in 2019. In 2019, the ASMR of smoking-attributed CVD was lowest in high SDI regions. CONCLUSION: Smoking-attributed CVD morbidity and mortality are declining globally, but significant variation persists, indicating a need for targeted interventions to reduce smoking-related CVD burden.

The burden of cardiovascular disease (CVD) attributed to smoking declined worldwide between 1990 and 2019. The burden of smoking-attributed CVD was higher in men than in women in 2019. There were significant variations between different countries and regions such that Eastern Europe had the highest death rate and Andean Latin America had the lowest death rate in 2019. Also, countries with high socio-economic status had lower death rates from smoking-attributed CVD. This highlights the need for targeted interventions to reduce the burden of smoking-attributed CVD. The overall age-adjusted deaths from CVD attributed to smoking declined from 57.16/100 000 in 1990 to 33.03/100 000 in 2019.In 2019, ischaemic heart disease was the leading cause of smoking-attributed CVD deaths.

Transformative Peer Connections: Early Experiences From the ASCO Palliative Care Community of Practice.

The integration of palliative care into routine oncology practice is the standard of care by most leading cancer organizations. Palliative medicine helps to deliver higher quality of care at a lower cost. However, there are barriers to implementing palliative oncology at many institutions for myriad reasons. In this article, we discuss an innovative strategy that ASCO implemented called the Communities of Practice (CoP). We share our experiences as the Palliative Care CoP and how our group seeks to develop processes and structures to collectively promote systemic change and enhance palliative care delivery for people with cancer. Our Palliative Care CoP engages with senior leaders, administrators, and those in power to achieve a shared vision of delivering holistic health care for people with serious illness. We continue to evolve to meet our members' growing needs by addressing eight main domains: (1) increasing palliative care education and resources; (2) creating opportunities for global palliative care research; (3) providing peer mentorship and community building; (4) engaging with patient advocates; (5) supporting and developing interdisciplinary teams; (6) assisting with professional development and identity formation, especially for trainees and early career faculty; (7) extending our outreach through social media; and (8) enhancing the clinical practice of palliative oncology. The ASCO CoP has been a vital forum to realize ASCO's mission of conquering cancer and advancing the Art and Science of Cancer Care: From Comfort to Cure.

Integrated dual training in palliative care and oncology.

Fellowship training in Hospice and Palliative Medicine (HPM) and Hematology/Oncology (Hem/Onc) share common themes and roots in the holistic care of people living with cancer. As of 2021, approximately 630 physicians in the United States were board-certified in both HPM and Hem/Onc. There is increasing demand for an integrated fellowship pathway, and the inaugural integrated fellowship Match took place in 2022. We present the historical context of the overlap in HPM and Hem/Onc fellowship training, limitations of the standard training paradigm, and an overview of the recently developed integrated training pathway accredited by the Accreditation Council for Graduate Medical Education (ACGME). We explore applications of dual training in clinical care, program development, and research at the intersection of HPM and Hem/Onc. Finally, we consider challenges to the success and how best to assess the outcomes of this program. Integrated fellowship training in HPM and Hem/Onc is 1 avenue to develop a cohort of dual-trained physicians poised to effect broad cultural change in this important and evolving space. A subset of physicians with dual training has the potential to fill unmet needs by promoting enhanced patient-centered care, developing infrastructure for heightened collaboration between these distinct but closely related fields, and prioritizing research focused on advanced communication skills and symptom management for patients with cancer.