Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.

Association of Neighborhood Deprivation With Thrombolysis and Thrombectomy for Acute Stroke in a Health System With Universal Access.

BACKGROUND AND OBJECTIVES: The association between socioeconomic status and acute ischemic stroke treatments remain uncertain, particularly in countries with universal health care systems. This study aimed to investigate the association between neighborhood-level material deprivation and the odds of receiving IV thrombolysis or thrombectomy for acute ischemic stroke within a single-payer, government-funded health care system. METHODS: We conducted a population-based cohort study using linked administrative data from Ontario, Canada. This study involved all community-dwelling adult Ontario residents hospitalized with acute ischemic stroke between 2017 and 2022. Neighborhood-level material deprivation, measured in quintiles from least to most deprived, was our main exposure. We considered the receipt of thrombolysis or thrombectomy as the primary outcome. We used multivariable logistic regression models adjusted for baseline differences to estimate the association between material deprivation and outcomes. We performed a sensitivity analysis by additionally adjusting for hospital type at initial assessment. Furthermore, we tested whether hospital type modified the associations between deprivation and outcomes. RESULTS: Among 57,704 patients, those in the most materially deprived group (quintile 5) were less likely to be treated with thrombolysis or thrombectomy compared with those in the least deprived group (quintile 1) (16.6% vs 19.6%, adjusted odds ratio [aOR] 0.76, 95% CI 0.63-0.93). The association was consistent when evaluating thrombolysis (13.0% vs 15.3%, aOR 0.78, 95% CI 0.64-0.96) and thrombectomy (6.4 vs 7.8%, aOR 0.73, 95% CI 0.59-0.90) separately. There were no statistically significant differences between the middle 3 quintiles and the least deprived group. These associations persisted after additional adjustment for hospital type, and there was no interaction between material deprivation and hospital type (p interaction >0.1). DISCUSSION: We observed disparities in the use of thrombolysis or thrombectomy for acute ischemic stroke by socioeconomic status despite access to universal health care. Targeted health care policies, public health messaging, and resource allocation are needed to ensure equitable access to acute stroke treatments for all patients.

Treatment outcomes for newly diagnosed, treatment-naïve TP53-mutated acute myeloid leukemia: a systematic review and meta-analysis.

BACKGROUND: TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA). METHODS: We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), duration of response (DoR), and overall response rate (ORR) among patients with TP53m AML receiving first-line treatment with IC, HMA, or VEN + HMA. RESULTS: Searches of EMBASE and MEDLINE identified 3006 abstracts, and 17 publications describing 12 studies met the inclusion criteria. Random-effects models were used to pool response rates, and time-related outcomes were analyzed with the median of medians method. IC was associated with the greatest CR rate of 43%, and CR rates were 33% for VEN + HMA and 13% for HMA. Rates of CR/CRi were comparable for IC (46%) and VEN + HMA (49%) but were lower for HMA (13%). Median OS was uniformly poor across treatments: IC, 6.5 months; VEN + HMA, 6.2 months; and HMA, 6.1 months. For IC, the EFS estimate was 3.7 months; EFS was not reported for VEN + HMA or HMA. The ORR was 41% for IC, 65% for VEN + HMA, and 47% for HMA. DoR was 3.5 months for IC, 5.0 months for VEN + HMA, and was not reported for HMA. CONCLUSIONS: Despite improved responses seen with IC and VEN + HMA compared to HMA, survival was uniformly poor, and clinical benefits were limited across all treatments for patients with newly diagnosed, treatment-naïve TP53m AML, demonstrating a significant need for improved treatment for this difficult-to-treat population.

Azacitidine Monotherapy in Patients With Treatment-Naïve Higher-risk Myelodysplastic Syndrome: A Systematic Literature Review and Meta-analysis.

BACKGROUND: The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes. MATERIALS AND METHODS: We assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for patients treated with AZA monotherapy. Noncomparative meta-analyses were used to summarize effects. RESULTS: The search identified 3250 abstracts, of which 34 publications describing 16 studies (5 RCTs, 3 prospective, and 8 retrospective observational) were included. Across all studies, pooled CR was 16%; PR was 6%; Median OS was 16.4 months; median DOR was 10.1 months; median TTR was 4.6 months. Proportions of grade 3/4 anemia and thrombocytopenia AEs were 10% and 30%. CONCLUSIONS: The effectiveness and efficacy of AZA monotherapy-as measured by CR and median OS-was limited. These findings highlight a significant unmet medical need for effective treatments for patients with higher-risk MDS.