Association Between the Use of an Adaptive Cardiac Resynchronization Therapy Algorithm and Health Care Use and Cost.

OBJECTIVES: To assess the association between the use of adaptive pacing on clinical and economic outcomes of cardiac resynchronization therapy (CRT) recipients in a real-world analysis. BACKGROUND: The adaptivCRT (aCRT) algorithm was shown in prior subgroup analyses of prospective trials to achieve clinical benefits, but a large prospective trial showed nonsignificant changes in the endpoint of mortality or hospitalizations due to heart failure. METHODS: CRT-implanted patients from the Optum Clinformatics database with ≥ 90 days of follow-up were included. Remote monitoring data were used to classify patients based on CRT setting-adaptive biventricular and left ventricular pacing (aCRT) vs standard biventricular pacing (Standard CRT). Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Mortality, 30-day readmissions, health care use, and payer and patients' costs were evaluated post-implantation. RESULTS: This study included 2412 aCRT and 1638 Standard CRT patients (mean follow-up: 2.4 ± 1.4 years), with balanced baseline characteristics after adjustment. The aCRT group was associated with lower all-cause mortality rates (adjusted hazard ratio = 0.88 [95% confidence interval (CI):0.80, 0.96]), fewer all-cause 30-day readmissions (adjusted incidence rate ratio = 0.87 [CI:0.81, 0.94]), and fewer all-cause and HF-related inpatient, outpatient and emergency department visits. The aCRT cohort was also associated with lower all-cause outpatient payer-paid amounts and lower all-cause and HF-related inpatient and emergency department patient-paid amounts. CONCLUSIONS: In this retrospective analysis of a large real-world cohort, the use of an adaptive CRT algorithm was associated with lower mortality rates, reduced health care resource use and lower payer and patient costs.

Assessment of the E-value in the presence of bias amplification: a simulation study.

BACKGROUND: The E-value, a measure that has received recent attention in the comparative effectiveness literature, reports the minimum strength of association between an unmeasured confounder and the treatment and outcome that would explain away the estimated treatment effect. This study contributes to the literature on the applications and interpretations of E-values by examining how the E-value is impacted by data with varying levels of association of unobserved covariates with the treatment and outcome measure when covariate adjustment is applied. We calculate the E-value after using regression and propensity score methods (PSMs) to adjust for differences in observed covariates. Propensity score methods are a common observational research method used to balance observed covariates between treatment groups. In practice, researchers may assume propensity score methods that balance treatment groups across observed characteristics will extend to balance of unobserved characteristics. However, that assumption is not testable and has been shown to not hold in realistic data settings. We assess the E-value when covariate adjustment affects the imbalance in unobserved covariates. METHODS: Our study uses Monte Carlo simulations to evaluate the impact of unobserved confounders on the treatment effect estimates and to evaluate the performance of the E-Value sensitivity test with the application of regression and propensity score methods under varying levels of unobserved confounding. Specifically, we compare observed and unobserved confounder balance, odds ratios of treatment vs. control, and E-Value sensitivity test statistics from generalized linear model (GLM) regression models, inverse-probability weighted models, and propensity score matching models, over correlations of increasing strength between observed and unobserved confounders. RESULTS: We confirm previous findings that propensity score methods - matching or weighting - may increase the imbalance in unobserved confounders. The magnitude of the effect depends on the strength of correlation between the confounder, treatment, and outcomes. We find that E-values calculated after applying propensity score methods tend to be larger when unobserved confounders result in more biased treatment effect estimates. CONCLUSIONS: The E-Value may misrepresent the size of the unobserved effect needed to change the magnitude of the association between treatment and outcome when propensity score methods are used. Thus, caution is warranted when interpreting the E-Value in the context of propensity score methods.

Outcomes of patients implanted with an atrioventricular synchronous leadless ventricular pacemaker in the Medicare population.

BACKGROUND: The Micra AV Coverage with Evidence Development study is a novel analysis of utilization and outcomes associated with Micra AV leadless pacing in US Medicare patients. OBJECTIVE: The purpose of this study was to describe patient characteristics, complications, and outcomes of patients implanted with a Micra AV leadless pacemaker compared with a contemporaneous cohort of patients implanted with a dual chamber transvenous pacemaker. METHODS: Patients implanted with Micra AV (n = 7471) or a dual chamber transvenous pacemaker (n = 107,800) from February 5, 2020, through December 1, 2021, were identified using device registry-linked Medicare claims data. Acute complications were assessed at 30 days, and chronic complications, reinterventions, and all-cause mortality were assessed at 6 months. RESULTS: Patients implanted with Micra AV had higher rates of end-stage renal disease (14.9% vs 2.0%; P < .0001) and overall comorbidity burden (mean Charlson Comorbidity Index 4.9 vs 3.8; P < .0001). There was no difference in the unadjusted rate of complications at 30 days (9.1% vs 8.7%; P = .61), and patients implanted with Micra AV had a significantly lower adjusted rate of complications (8.6% vs 11.0%; P < .0001). At 6 months, patients implanted with Micra AV had significantly lower rates of complications (adjusted hazard ratio 0.50; 95% confidence interval 0.43-0.57; P < .0001) and reinterventions (adjusted hazard ratio 0.46; 95% confidence interval 0.36-0.58; P < .0001). Patients implanted with Micra AV had higher all-cause mortality at 30 days and 6 months, likely because of differences in the underlying risk of mortality. CONCLUSION: Patients implanted with Micra AV had similar rates of complications at 30 days and significantly lower rates of complications and reinterventions at 6 months, despite being sicker than patients implanted with a transvenous pacemaker.

Leadless versus transvenous single-chamber ventricular pacemakers: 3 year follow-up of the Micra CED study.

INTRODUCTION: The Micra Coverage with Evidence Development (CED) Study is a novel comparative analysis of Micra (leadless VVI) and transvenous single-chamber ventricular pacemakers (transvenous VVI) using administrative claims data. To compare chronic complications, device reinterventions, heart failure hospitalizations, and all-cause mortality after 3 years of follow-up. METHODS: US Medicare claims data linked to manufacturer device registration information were used to identify Medicare beneficiaries with a de novo implant of either a Micra VR leadless VVI or transvenous VVI pacemaker from March 9, 2017 to December 31, 2018. Unadjusted and propensity score overlap-weight adjusted Fine-Gray competing risk models were used to compare outcomes at 3 years. RESULTS: Leadless VVI patients (N = 6219) had a 32% lower rate of chronic complications and a 41% lower rate of reintervention compared with transvenous VVI patients (N = 10 212) (chronic complication hazard ratio [HR] 0.68; 95% confidence interval [CI], 0.59-0.78; reintervention HR 0.59; 95% CI 0.44-0.78). Infections rates were significantly lower among patients with a leadless VVI (<0.2% vs. 0.7%, p < .0001). Patients with a leadless VVI also had slightly lower rates of heart failure hospitalization (HR 0.90; 95% CI 0.84-0.97). There was no difference in the adjusted 3-year all-cause mortality rate (HR 0.97; 95% CI, 0.92-1.03). CONCLUSION: This nationwide comparative evaluation of leadless VVI versus transvenous VVI de novo pacemaker implants demonstrated that the leadless group had significantly fewer complications, reinterventions, heart failure hospitalizations, and infections than the transvenous group at 3 years, confirming that the previously reported shorter-term advantages associated with leadless pacing persist and continue to accrue in the medium-to-long-term.

Two-year outcomes of leadless vs. transvenous single-chamber ventricular pacemaker in high-risk subgroups.

AIMS: This study compares clinical outcomes between leadless pacemakers (leadless-VVI) and transvenous ventricular pacemakers (transvenous ventricular permanent-VVI) in subgroups of patients at higher risk of pacemaker complications. METHODS AND RESULTS: This study is based on the Micra Coverage with Evidence Development (CED) study. Patients from the Micra CED study were considered in a high-risk subgroup if they had a diagnosis of chronic kidney disease Stages 4-5 (CKD45), end-stage renal disease, malignancy, diabetes, tricuspid valve disease (TVD), or chronic obstructive pulmonary disease (COPD) 12 months prior to pacemaker implant. A pre-specified set of complications and reinterventions were identified using diagnosis and procedure codes. Competing risks models were used to compare reinterventions and complications between leadless-VVI and transvenous-VVI patients within each subgroup; results were adjusted for multiple comparisons. A post hoc comparison of a composite outcome of reinterventions and device complications was conducted. Out of 27 991 patients, 9858 leadless-VVI and 12 157 transvenous-VVI patients have at least one high-risk comorbidity. Compared to transvenous-VVI patients, leadless-VVI patients in four subgroups [malignancy, HR 0.68 (0.48-0.95); diabetes, HR 0.69 (0.53-0.89); TVD, HR 0.60 (0.44-0.82); COPD, HR 0.73 (0.55-0.98)] had fewer complications, in three subgroups [diabetes, HR 0.58 (0.37-0.89); TVD, HR 0.46 (0.28-0.76); COPD, HR 0.51 (0.29-0.90)) had fewer reinterventions, and in four subgroups (malignancy, HR 0.52 (0.32-0.83); diabetes, HR 0.52 (0.35-0.77); TVD, HR 0.44 (0.28-0.70); COPD, HR 0.55 (0.34-0.89)] had lower rates of the combined outcome. CONCLUSION: In a real-world study, leadless pacemaker patients had lower 2-year complications and reinterventions rates compared with transvenous-VVI pacing in several high-risk subgroups. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03039712.

Collection of economic data using UB-04s: Is it worth the effort? Evidence from two clinical trials.

Cost collection using UB-04 forms for economic evaluation is challenging, as UB-04 collection is time and effort intensive and compliance is imperfect. Alternative data sources could overcome those challenges. The objective of this study is to determine the usefulness of UB-04 data in estimating hospital costs compared to clinical case report form (CRF) data. Health care utilization costs were compared from financial information in UB-04s and from an assignment process using CRF data, from the WRAP-IT (23 infections) and the Micra IDE trials (61 adverse events and 108 implants). Charge-based costs were calculated by multiplying charges in UB-04s and hospital-specific Cost-to-Charge ratios from the Centers for Medicare and Medicaid Services cost reports. The cost assignment process used clinical information to find comparable encounters in real world data and assigned an average cost. Paired difference tests evaluated whether both methods yield similar results. The mean difference in total infection related costs between methods in the WRAP-IT trial was $152 +/-$22,565. In the Micra IDE trial, the mean difference in total adverse event related costs between methods was -$355 +/-$8,298 while the mean difference in total implant related costs between methods was $-3,488 +/-$13,859. Wilcoxon tests and generalized linear models could not reject the difference in costs between methods in the first two cases. Cost assignment methods achieve results similar to costs obtained through UB-04s, without the additional investment in time and effort. The use of UB-04 information for services that are not mature in a health care system may present unexpected challenges, necessitating a tradeoff with other methods of cost assignment.

Diagnostic sensitivity and cost per diagnosis of ambulatory cardiac monitoring strategies in unexplained syncope patients.

Diagnosing cardiac pauses that could produce syncopal episodes is important to guide appropriate therapy. However, the infrequent nature of these episodes can make detection challenging with conventional monitoring (CM) strategies with short-term ECG monitors. Insertable cardiac monitors (ICMs) continuously monitor for arrhythmias but present a higher up-front cost. It is not well understood whether these higher costs are offset by the costs of repeat evaluation in CM strategies. We simulated the likelihood of diagnostic success and cost-per-diagnosis of pause arrhythmias with CM strategies compared to ICM monitoring. ICM device data from syncope patients diagnosed with pause arrhythmias was utilized to simulate patient pathways and diagnostic success with CM. We assumed that detected true pause episodes (≥5 seconds) were symptomatic and prompted a hospital encounter and further evaluation with CM. Subsequent true pause episodes in yet-undiagnosed patients triggered additional rounds of CM. Costs of monitoring were accrued at each encounter and represent the U.S. payer perspective. Cost per diagnosed patient was calculated as the total costs accrued for all patients divided by the number of patients diagnosed, across 1,000 simulations. During a mean 505±333 days of monitoring ICM detected 2.4±2.7 pause events per patient, with an average of 109±94 days until the first event. CM was projected to diagnose between 13.8% (24-hour Holter) and 30.2% (two 30-day monitors) of the ICM-diagnosed patients. Total diagnostic costs per ICM-diagnosed patient averaged $7,847, whereas in the CM strategies average cost-per-diagnosis ranged from $12,950±2,589 with 24-hour Holter to $32,977±14,749 for two 30-day monitors. Relative to patients diagnosed with pause arrhythmias via ICM, CM strategies diagnose fewer patients and incur higher costs per diagnosed patient.

Leadless vs. transvenous single-chamber ventricular pacing in the Micra CED study: 2-year follow-up.

AIMS: Clinical trials have demonstrated the safety and efficacy of the Micra leadless VVI pacemaker; however, longer-term outcomes in a large, real-world population with a contemporaneous comparison to transvenous VVI pacemakers have not been examined. We compared reinterventions, chronic complications, and all-cause mortality at 2 years between leadless VVI and transvenous VVI implanted patients. METHODS AND RESULTS: The Micra Coverage with Evidence Development study is a continuously enrolling, observational, cohort study of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted with a leadless VVI pacemaker between March 9, 2017, and December 31, 2018, were identified using Medicare claims data linked to manufacturer device registration data (n = 6219). All transvenous VVI patients from facilities with leadless VVI implants during the study period were obtained directly from Medicare claims (n = 10 212). Cox models were used to compare 2-year outcomes between groups. Compared to transvenous VVI, patients with leadless VVI had more end-stage renal disease (12.0% vs. 2.3%) and a higher Charlson comorbidity index (5.1 vs. 4.6). Leadless VVI patients had significantly fewer reinterventions [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45-0.85, P = 0.003] and chronic complications (adjusted HR 0.69, 95% CI 0.60-0.81, P < 0.0001) compared with transvenous VVI patients. Adjusted all-cause mortality at 2 years was not different between the two groups (adjusted HR 0.97, 95% CI 0.91-1.04, P = 0.37). CONCLUSION: In a real-world study of US Medicare patients, the Micra leadless VVI pacemaker was associated with a 38% lower adjusted rate of reinterventions and a 31% lower adjusted rate of chronic complications compared with transvenous VVI pacing. There was no difference in adjusted all-cause mortality at 2 years.

Compassionate use of cefiderocol to treat tissue infection caused by MDR-pseudomonas aeruginosa in a critically-ill patient / Uso compasivo de cefiderocol en el tratamiento de pseudomona multirresistentes en paciente crítico

BACKGROUND: One of the newest antibiotics against multidrug-resistant (MDR) bacteria is Cefiderocol, a siderophore cephalosporin able to overcome most resistance mechanisms, including metallo-beta-lactamases. Several studies are being carried to prove its clinical benefit. CASE PRESENTATION: A 55-year-old male patient was admitted in the ICU undergoing septic shock due to surgical wound infection. Multidrug-resistant Pseudomonasputida grew in blood cultures and Pseudomonas aeruginosa grew in soft tissue cultures. He was treated with colistin and tobramycin, developing nephro and ototoxicity. Compassionate use of cefiderocol was ordered, and the infection was cured within 14 days. CONCLUSIONS: This is the first evidence of cefiderocol treatment in a soft tissue infection within a surgical wound infection. Our experience with cefiderocol in surgical wound infection suggests that it may be helpful in treating infections at that level, but more clinical trials are still needed.

ANTECEDENTES: Uno de los antibióticos más nuevos contra las bacterias multirresistentes (MDR) es el cefiderocol, una cefalos- porina siderófora capaz de superar la mayoría de los mecanismos de resistencia, incluidas las metalobetalactamasas. Se están realizando varios estudios para demostrar su beneficio clínico. PRESENTACIÓN DEL CASO: Paciente masculino de 55 años que ingresó en la UCI con shock séptico por infección de herida quirúrgica. Pseudomonas putida multirresistente creció en hemocultivos y Pseudomonas aeruginosa crecieron en cultivos de tejidos blandos. Fue tratado con colistina y tobramicina, desarrollando nefro y ototoxicidad. Se indicó cefiderocol y la infección se curó en 14 días. CONCLUSIONES: Esta es la primera evidencia de cefiderocol en el tratamiento de una infección de partes blandas dentro de una infección de herida quirúrgica. Nuestra experiencia con cefiderocol en infección de herida quirúrgica sugiere que puede ser útil en el tratamiento de infecciones a ese nivel, pero aún se necesitan más ensayos clínicos.

Pupilometría óptica cuantitativa en cuidados intensivos / Quantitative optical pupillometry in intensive care unit

Neurological examination is still one of the most important semiological aspects in the daily assessment of the critically ill patient, especially in those with acute neurological injury. Within the neurological examination, the pupillary examination, including size, symmetry, and reactivity to light stimulus, is one of the most fundamental aspects and with the greatest weight when it comes to predict the neurological outcome[]. Conventional pupillary assessment is based on a qualitative, subjective, explorer- dependent method, with great inter-explorer variability and therefore, subject to errors during its performance and interpretation[]. In the modern era, the incorporation of new technologies in the field of critically ill patients has made us focus more on a personalized and more precise medicine, leaving behind the traditional examination practices to be replaced by diagnostic tools that facilitate work and overcome the human factor of the equation, thanks to the quantitative optical pupillometry (POC) by infrared.

La exploración neurológica sigue siendo uno de los aspectos semiológicos más importantes en la evaluación rutinaria del enfermo crítico, sobre todo en pacientes con patología aguda neurológica. Dentro de la exploración neurológica, el examen pupilar, incluyendo el tamaño, simetría y la reactividad pupilar a la luz, es uno de los aspectos más fundamentales y con mayor peso a la hora de predecir trastornos neurológicos agudos, e incluso para predecir el pronóstico neurológico[]. La exploración pupilar convencional se basa en un método cualitativo, subjetivo, explorador dependiente, con gran variabilidad interexplorador y, por lo tanto, sujeto a errores durante su realización e interpretación[]. En la era moderna, la incorporación de nuevas tecnologías en el ámbito del paciente crítico, han hecho que nos enfoquemos más en una medicina personalizada y más precisa, dejando relegadas las prácticas de exploración tradicionales para ser sustituidas por herramientas diagnósticas que facilitan el trabajo y eliminan el factor humano de la ecuación, entre estas se encuentra la pupilometría óptica cuantitativa (POC) por infrarrojos.

Cost-Effectiveness Analysis of Implantable Cardioverter Defibrillator Therapy for Primary Prevention Patients with Additional Risk Factors in Brazil

Abstract Background: Implantable cardiac defibrillators (ICDs) therapy for primary prevention (PP) of sudden cardiac arrest (SCA) is well-established but underutilized globally. The Improve SCA study has identified a cohort of patients called 1.5 primary prevention (1.5PP), based on PP patients with the presence of documented risk factors: non-sustained ventricular tachycardia, frequent premature ventricular contractions, left ventricular ejection fraction < 25%, and pre-syncope or syncope. Objective: This study evaluated the cost-effectiveness of ICD therapy compared to no ICD among 1.5PP patients in the Brazilian public healthcare system. Methods: Modified inputs to a published Markov model were applied to compare costs and outcomes of ICD therapy to no ICD therapy from the Brazilian payer's perspective. Mortality and utility estimates were obtained from the IMPROVE SCA trial. Additional effectiveness inputs were sourced from the literature. Cost inputs were obtained from the Brazilian Unified Health System and the Ministry of Health. Costs were discounted at 4.7%; quality-adjusted life years (QALYs) were discounted at 1.45%. This study applied a willingness-to-pay (WTP) value of three times Brazil's gross domestic product (GDP) in 2017, R$105,723 (Brazilian Real). Results: The total discounted lifetime costs for ICD therapy were R$100,920 compared to R$43,866 for no ICD therapy. Total discounted QALYs for ICD therapy and no ICD therapy were 9.85 and 7.15, respectively. The incremental cost effectiveness ratio was R$21,156 per QALY and less than the R$105,723 WTP threshold. Results from sensitivity analyses were consistent with base case results. Conclusions: ICD therapy compared to no ICD therapy is cost-effective in the 1.5PP population in Brazil. (Int J Cardiovasc Sci. 2021; [online].ahead print, PP.0-0)