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Abstract The clinical application of Pharmacogenomics (PGx) has improved patient safety. However, comprehensive PGx testing has not been widely adopted in clinical practice, and significant opportunities exist to further optimize PGx in cancer care. This systematic review and meta‐analysis aim to evaluate the safety outcomes of reported PGx‐guided strategies (Analysis 1) and identify well‐studied emerging pharmacogenomic variants that predict severe toxicity and symptom burden (Analysis 2) in patients with cancer. We searched MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to January 2023 for clinical trials or comparative studies evaluating PGx strategies or unconfirmed pharmacogenomic variants. The primary outcomes were severe adverse events (SAE; ≥ grade 3) or symptom burden with pain and vomiting as defined by trial protocols and assessed by trial investigators. We calculated pooled overall relative risk (RR) and 95% confidence interval (95%CI) using random effects models. PROSPERO, registration number CRD42023421277. Of 6811 records screened, six studies were included for Analysis 1, 55 studies for Analysis 2. Meta‐analysis 1 (five trials, 1892 participants) showed a lower absolute incidence of SAEs with PGx‐guided strategies compared to usual therapy, 16.1% versus 34.0% (RR = 0.72, 95%CI 0.57–0.91, p = 0.006, I2 = 34%). Meta‐analyses 2 identified nine medicine(class)‐variant pairs of interest across the TYMS, ABCB1, UGT1A1, HLA‐DRB1, and OPRM1 genes. Application of PGx significantly reduced rates of SAEs in patients with cancer. Emergent medicine‐variant pairs herald further research into the expansion and optimization of PGx to improve systemic anti‐cancer and supportive care medicine safety and efficacy.

BackgroundAcute decompensated heart failure (HF) and cardiogenic shock (CS) frequently are refractory to conservative treatment and require mechanical circulatory support (MCS). We report our early clinical experience and evaluate patient outcomes with the newer generation surgical Impella 5.5.MethodsSeventy patients that underwent Impella 5.5 implantation between October 2019 and December 2021 at a single center were enrolled in this study. Pre-operative characteristics, peri-operative clinical course information, and post-operative outcomes were retrospectively collected.ResultsFifty-seven (81%) patients survived to discharge, and 51 (76%) patients survived at the time of the first 30 days post-discharge visit. Thirty-one patients (44%) received Impella support for a bridge to advanced surgical heart failure therapy (transplant or durable left ventricular assist device [LVAD]), 27 (39%) cases were used for a bridge to recovery/decision and 12 (17.1%) cases was used for planned perioperative support for high-risk cardiac surgery procedure.ConclusionOur results suggest that Impella 5.5 provides favorable survival in the management of HF and CS, particularly used for a bridge to heart transplant or LVAD. Early extubation and mobilization with high flow circulatory support allowed effective tailoring of MCS approaches from peri-operative support for high-risk cardiac surgery, bridge to recovery, and to advanced surgical heart failure therapy.

Background Peripartum cardiomyopathy (PPCM) outcomes have been previously linked to demographic and social factors. The social vulnerability index (SVI) is a measure of social vulnerability in the United States. We explored PPCM disparities and the impact of SVI on PPCM mortality. Methods and Results Mortality from 1999 to 2020, SVI, and demographic data were obtained from CDC databases. County‐specific SVI rankings were linked to PPCM age‐adjusted mortality rates (AAMRs), allowing for a comparative analysis of AAMRs across both cumulative populations and subpopulations to identify disparities. All US counties were then stratified into low‐ and high‐SVI groups, facilitating comparison of SVI rankings by estimation of excess‐deaths per 1 000 000 person‐years attributable to greater social vulnerability and rate ratios (RR) through univariable Poisson regression. We identified a total of 1026 deaths related to PPCM between 1999 and 2020. Overall AAMR increased from 0.180 in 1999 to 0.326 in 2020. Black populations (AAMR: 1.081) and Southern US counties (AAMR: 0.444) had the highest AAMRs compared with other racial and US census groups, respectively. Higher SVI accounted for 0.172 excess deaths per 1 000 000 person‐years (RR=1.800). Among Black and White populations, higher SVI also accounted for 0.248 and 0.071 excess deaths per 1 000 000 person‐years, respectively. Similar impacts of greater social vulnerability were observed when comparing the US census regions (Northeast RR=1.609, Midwest RR=1.819, South RR=1.934, West RR=1.776). Conclusions PPCM mortality disparities exist across racial and geographic populations in the United States. A greater burden of social vulnerability is associated with higher PPCM mortality on a national level.

Abstract Background The impact of chronic kidney disease (CKD) on atrial fibrillation outcomes (AF) is not well understood. Methods We conducted analyses of comorbid AF and CKD related death in the United States from 1999 to 2020 using descriptive epidemiology. Results Age‐adjusted mortality rates (AAMR) per 100,000 increased from 0.39 in 1999 to 1.65 in 2020. Non‐Hispanic populations (1.01) and nonmetropolitan areas (1.08) had higher AAMRs compared to Hispanic (0.62) and metropolitan (0.97) areas. Midwestern (1.11) and Western (1.13) US regions recorded the highest AAMRs. Conclusions These findings highlight the need for interventions to address AF death disparities in patients with CKD.

Background: Social vulnerability index (SVI) plays a pivotal role in the outcomes of cardiovascular diseases and prevalence of alcohol use. We evaluated the impact of the SVI on alcoholic cardiomyopathy (ACM) mortality. Methods: Mortality data from 1999 to 2020 and the SVI were obtained from CDC databases. Demographics such as age, sex, race/ethnicity, and geographic residence were obtained from death certificates. The SVI was divided into quartiles, with the fourth quartile (Q4) representing the highest vulnerability. Age-adjusted mortality rates across SVI quartiles were compared, and excess deaths due to higher SVI were calculated. Risk ratios were calculated using univariable Poisson regression. Results: A total of 2779 deaths were seen in Q4 compared to 1672 deaths in Q1. Higher SVI accounted for 1107 excess-deaths in the US and 0.05 excess deaths per 100,000 person-years (RR: 1.38). Similar trends were seen for both male (RR: 1.43) and female (RR: 1.67) populations. Higher SVI accounted for 0.06 excess deaths per 100,000 person-years in Hispanic populations (RR: 2.50) and 0.06 excess deaths per 100,000 person-years in non-Hispanic populations (RR: 1.46). Conclusion: Counties with elevated SVI experienced higher ACM mortality rates. Recognizing the impact of SVI on ACM mortality can guide targeted interventions and public health strategies, emphasizing health equity and minimizing disparities.

Billing and insurance-related costs are a significant source of wasteful health care spending in Organization for Economic Cooperation and Development nations, but these administrative burdens vary across national systems. We executed a microlevel accounting of these costs in different national settings at six provider locations in five nations (Australia, Canada, Germany, the Netherlands, and Singapore) that supplements our prior study measuring the costs in the US. We found that billing and insurance-related costs for inpatient bills range from a low of $6 in Canada to a high of $215 in the US for an inpatient surgical bill (purchasing power parity adjusted). We created a taxonomy of billing and insurance-related activities (eligibility, coding, submission, and rework) that was applied to data from the six sites and allows cross-national comparisons. Higher costs in the US and Australia are attributed to high coding costs. Much of the savings achieved in some nations is attributable to assigning tasks to people in lower-skill job categories, although most of the savings are due to more efficient billing and insurance-related processes. Some nations also reduce these costs by offering financial counseling to patients before treatment. Our microlevel approach can identify specific cost drivers and reveal national billing features that reduce coding costs. It illustrates a valuable pathway for future research in understanding and mitigating administrative costs in health care.