Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults.

INTRODUCTION: Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). METHODS: This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. RESULTS: In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506-0.887), 29.3% (0.707; 0.573-0.858), and 23.4% (0.766; 0.626-0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860-0.976), 6.4% (0.936; 0.895-0.978), and 2.4% (0.976; 0.935-1.017), respectively. CONCLUSIONS: Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.

Classification, Prediction, and Concordance of Cognitive and Functional Progression in Patients with Mild Cognitive Impairment in the United States: A Latent Class Analysis.

BACKGROUND: Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood. OBJECTIVE: To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class. METHODS: Participants with incident MCI were identified from the US National Alzheimer's Coordinating Center Uniform Data Set (09/2005-02/2019). Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Predictors of progression class were identified using multivariate multinomial logistic regression models; odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus≤70 years, OR [95% CI] = 5.26 [1.78-15.54]), one copy of APOE ɛ4 (1.94 [1.08-3.47]), higher baseline CDR-SB (2.46 [1.56-3.88]), lower baseline MMSE (0.85 [0.75-0.97]), and higher baseline FAQ (1.13 [1.02-1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p < 0.05). Predictors of FAQ class membership were largely similar. CONCLUSION: Approximately a third of participants experienced progression based on CDR-SB or FAQ during the  4-year follow-up period. CDR-SB and FAQ class assignment were concordant for the vast majority of participants. Identified predictors may help the selection of patients at higher risk of progression in future trials.

The Impact of Progression on Healthcare Resource Utilization and Costs Among Patients with High-Grade Non-Muscle Invasive Bladder Cancer After Bacillus Calmette-Guérin Therapy: A Retrospective SEER-Medicare Analysis.

INTRODUCTION: We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy. METHODS: Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. RESULTS: Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]. CONCLUSIONS: Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.

Real-world systemic therapy utilization in Medicare patients with locally advanced or metastatic urothelial carcinoma diagnosed between 2008 and 2012.

PURPOSE: Treatment of advanced urothelial carcinoma (UC) remains a challenging clinical entity occurring predominantly in older patients with limited treatment options. However, real-world treatment patterns, differential cancer center access, and association with outcomes is lacking in nationally representative clinical practice and will provide context for emerging therapies. MATERIALS AND METHODS: We used SEER-Medicare data to identify patients with locally advanced or metastatic UC of the bladder or upper urinary tract diagnosed between 2008 and 2012. We characterized utilization systemic therapy, including first- and second-line chemotherapy. Patients receiving neoadjuvant chemotherapy were excluded; results were stratified by academic versus non-academic setting. RESULTS: 3569 patients met study criteria; 48% received some form of chemotherapy within 2 years of diagnosis. Of these, one-third subsequently received second-line chemotherapy. The majority received a regimen including ≥2 agents. Gemcitabine alone or in combination with platinum was the most common first- and second-line treatment. Similar patterns of first- and second-line chemotherapy were observed between patients treated in academic and non-academic centers. Sensitivity analyses of trial-similar patients demonstrated increased utilization (69%). Receipt of platinum doublet as 1st line therapy was less likely in older patients and those with renal disease, and more likely for grade IV disease. CONCLUSIONS: Roughly half of all Medicare patients with locally advanced/metastatic UC receive systemic therapy regardless of access to academic cancer centers and despite poor oncologic outcomes. Cytotoxic, gemcitabine-based doublet chemotherapy remains the most common treatment. A substantial population of older patients exists for whom alternative, non-cytotoxic, treatment options may be of benefit.

Evidence-based Assessment of Current and Emerging Bladder-sparing Therapies for Non-muscle-invasive Bladder Cancer After Bacillus Calmette-Guerin Therapy: A Systematic Review and Meta-analysis.

CONTEXT: Currently, there is no standard of care for patients with non-muscle-invasive bladder cancer (NMIBC) who recur despite bacillus Calmette-Guerin (BCG) therapy. Although radical cystectomy is recommended, many patients decline to undergo or are ineligible to receive it. Multiple agents are being investigated for use in this patient population. OBJECTIVE: To systematically synthesize and describe the efficacy and safety of current and emerging treatments for NMIBC patients after treatment with BCG. EVIDENCE ACQUISITION: A systematic literature search of MEDLINE, Embase, and the Cochrane Controlled Register of Trials (period limited to January 2007-June 2019) was performed. Abstracts and presentations from major conference proceedings were also reviewed. Randomized controlled trials were assessed using the Cochrane risk of bias tool. Data for single-arm trials were pooled using a random-effect meta-analysis with the proportions approach. Trials were grouped based on the minimum number of prior BCG courses required before enrollment and further stratified based on the proportion of patients with carcinoma in situ (CIS). EVIDENCE SYNTHESIS: Thirty publications were identified with data from 23 trials for meta-analysis, of which 17 were single arm. Efficacy and safety outcomes varied widely across studies. Heterogeneity across trials was reduced in subgroup analyses. The pooled 12-mo response rates were 24% (95% confidence interval [CI]: 16-32%) for trials with two or more prior BCG courses and 36% (95% CI: 25-47%) for those with one or more prior BCG courses. In a subgroup analysis, inclusion of ≥50% of patients with CIS was associated with a lower response. CONCLUSIONS: The variability in efficacy and safety outcomes highlights the need for consistent endpoint reporting and patient population definitions. With promising emerging treatments currently in development, efficacious and safe therapeutic options are urgently needed for this difficult-to-treat patient population. PATIENT SUMMARY: We examined the efficacy and safety outcomes of treatments for non-muscle-invasive bladder cancer after bacillus Calmette-Guerin therapy. Outcomes varied across studies and patient populations, but emerging treatments currently in development show promising efficacy.

Simulated Costs of the ASCO Patient-Centered Oncology Payment Model in Medicare Beneficiaries With Newly Diagnosed Advanced Ovarian Cancer.

PURPOSE: Efforts to curb the rising costs of cancer care while improving quality include alternative payment models (APMs), which offer incentives to reduce avoidable spending and provide high-quality and cost-efficient care. The impact of proposed APMs has not been quantified in real-world practice. In this study, we evaluated ASCO's Patient-Centered Oncology Payment (PCOP) model in existing fee-for-service (FFS) Medicare beneficiaries to understand the magnitude of potential cost savings. MATERIALS AND METHODS: SEER-Medicare data were used to identify women with advanced ovarian cancer diagnosed between 2000 and 2012 who either (1) underwent primary debulking surgery followed by chemotherapy or (2) received neoadjuvant chemotherapy followed by surgery. Medicare payments in each cohort were used to compare FFS and PCOP and to estimate the potential for cost savings across health care services received, including outpatient emergency department visits, hospitalizations, and imaging. RESULTS: Three thousand seven hundred seventy-seven primary debulking surgery and 866 neoadjuvant chemotherapy patients were included in the study, with mean total costs of $75,433 and $95,138 in 2016 US$, respectively Most costs were related to chemotherapy or hospitalization. Additional PCOP-related payments would be offset if hospitalizations could be reduced by 11.6% or imaging claims by 88%. CONCLUSION: APMs have the potential to reduce costs of current FFS reimbursement via either a large reduction in imaging or a modest reduction in hospitalizations during treatment of ovarian cancer. PCOP is a reasonable payment structure for oncologists if the additional payments can provide the necessary resources to invest in improved coordination of care.

Comparison of the Harms, Advantages, and Costs Associated With Alternative Guidelines for the Evaluation of Hematuria.

IMPORTANCE: Existing recommendations for the diagnostic testing of hematuria range from uniform evaluation of varying intensity to patient-level risk stratification. Concerns have been raised about not only the costs and advantages of computed tomography (CT) scans but also the potential harms of CT radiation exposure. OBJECTIVE: To compare the advantages, harms, and costs associated with 5 guidelines for hematuria evaluation. DESIGN, SETTING, AND PARTICIPANTS: A microsimulation model was developed to assess each of the following guidelines (listed in order of increasing intensity) for initial evaluation of hematuria: Dutch, Canadian Urological Association (CUA), Kaiser Permanente (KP), Hematuria Risk Index (HRI), and American Urological Association (AUA). Participants comprised a hypothetical cohort of patients (n = 100 000) with hematuria aged 35 years or older. This study was conducted from August 2017 through November 2018. EXPOSURES: Under the Dutch and CUA guidelines, patients received cystoscopy and ultrasonography if they were 50 years or older (Dutch) or 40 years or older (CUA). Under the KP and HRI guidelines, patients received different combinations of cystoscopy, ultrasonography, and CT urography or no evaluation on the basis of risk factors. Under the AUA guidelines, all patients 35 years or older received cystoscopy and CT urography. MAIN OUTCOMES AND MEASURES: Urinary tract cancer detection rates, radiation-induced secondary cancers (from CT radiation exposure), procedural complications, false-positive rates per 100 000 patients, and incremental cost per additional urinary tract cancer detected. RESULTS: The simulated cohort included 100 000 patients with hematuria, aged 35 years or older. A total of 3514 patients had urinary tract cancers (estimated prevalence, 3.5%; 95% CI, 3.0%-4.0%). The AUA guidelines missed detection for the fewest number of cancers (82 [2.3%]) compared with the detection rate of the HRI (116 [3.3%]) and KP (130 [3.7%]) guidelines. However, the simulation model projected 108 (95% CI, 34-201) radiation-induced cancers under the KP guidelines, 136 (95% CI, 62-229) under the HRI guidelines, and 575 (95% CI, 184-1069) under the AUA guidelines per 100 000 patients. The CUA and Dutch guidelines missed detection for a larger number of cancers (172 [4.9%] and 251 [7.1%]) but had 0 radiation-induced secondary cancers. The AUA guidelines cost approximately double the other 4 guidelines ($939/person vs $443/person for Dutch guidelines), with an incremental cost of $1 034 374 per urinary tract cancer detected compared with that of the HRI guidelines. CONCLUSIONS AND RELEVANCE: In this simulation study, uniform CT imaging for patients with hematuria was associated with increased costs and harms of secondary cancers, procedural complications, and false positives, with only a marginal increase in cancer detection. Risk stratification may optimize the balance of advantages, harms, and costs of CT.