Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.

Women's preference to apply shared decision-making in breast cancer screening: a discrete choice experiment.

OBJECTIVE: To analyse women's stated preferences for establishing the relative importance of each attribute of shared decision-making (SDM) and their willingness to pay (WTP) for more participatory care in breast cancer screening programmes (BCSP). DESIGN: A discrete choice experiment was designed with 12 questions (choice tasks). It included three attributes: 'How the information is obtained', regarding benefits and harms; whether there is a 'Dialogue for scheduled mammography' between the healthcare professional and the woman; and, 'Who makes the decision', regarding participation in BCSP. Data were obtained using a survey that included 12 choice tasks, 1 question on WTP and 7 socioeconomic-related questions. The analysis was performed using conditional mixed-effect logit regression and stratification according to WTP. SETTING: Data collection related to BCSP was conducted between June and November 2021 in Catalonia, Spain. PARTICIPANTS: Sixty-five women aged between 50 and 60. MAIN OUTCOME MEASURES: Women's perceived utility of each attribute, trade-off on these attributes and WTP for SDM in BCSP. RESULT: The only significant attribute was 'Who makes the decision'. The decision made alone (coefficient=2.879; 95% CI=2.297 to 3.461) and the decision made together with a healthcare professional (2.375; 95% CI=1.573 to 3.177) were the options preferred by women. The former contributes 21% more utility than the latter. Moreover, 52.3% of the women stated a WTP of €10 or more for SDM. Women's preferences regarding attributes did not influence their WTP. CONCLUSIONS: The participant women refused a current paternalistic model and preferred either SDM or informed decision-making in BCSP.

Quality of care indicators for a resuscitation unit: A descriptive study and proposal.

There are lack of indicators of quality of care in resuscitation units of emergency departments. With the aim of proposing a series of indicators to evaluate the quality of care delivered in hospital resuscitation areas, we conducted a descriptive study of 7579 admissions to the resuscitation unit of an emergency department at a Spanish hospital between 2012 and 2016. The proposed indicators were the percentage of patients attending to the emergency department admitted to the resuscitation area by level of triage, the length of stay, the percentage of patients moved to intensive care and surgery at disposition, the mortality in the area or in the emergency department within 24 hours of disposition, and the data completeness. A majority of the patients (62.6%) were men and the median age was 68 years. Over 99% of the required data were recorded. Median length of stay in the resuscitation unit was 0.87 hours (interquartile range, 0.5-1.5). Approximately 80% of patients categorized as an emergency on admission to the emergency department were admitted to the resuscitation unit, although the proportion of urgency patients was higher. The main disposition destination was a trauma cubicle (82.3% of cases). Mortality was 0.41%.Specific indicators are needed to assess the quality of care delivery in resuscitation units. We believe that our findings will provide new insights into the work done to date in this field.

Clinical variables impacting on the estimation of utilities in chronic obstructive pulmonary disease.

PURPOSE: Health utilities are widely used in health economics as a measurement of an individual's preference and show the value placed on different health states over a specific period. Thus, health utilities are used as a measure of the benefits of health interventions in terms of quality-adjusted life years. This study aimed to determine the demographic and clinical variables significantly associated with health utilities for chronic obstructive pulmonary disease (COPD) patients. PATIENTS AND METHODS: This was a multicenter, observational, cross-sectional study conducted between October 2012 and April 2013. Patients were aged ≥40 years, with spirometrically confirmed COPD. Utility values were derived from the preference-based generic questionnaire EQ-5D-3L applying weighted Spanish societal preferences. Demographic and clinical variables associated with utilities were assessed by univariate and multivariate linear regression models. RESULTS: Three hundred and forty-six patients were included, of whom 85.5% were male. The mean age was 67.9 (standard deviation [SD] =9.7) years and the mean forced expiratory volume in 1 second (%) was 46.2% (SD =15.5%); 80.3% were former smokers, and the mean smoking history was 54.2 (SD =33.2) pack-years. Median utilities (interquartile range) were 0.81 (0.26) with a mean value of 0.73 (SD =0.29); 22% of patients had a utility value of 1 (ceiling effect) and 3.2% had a utility value lower than 0. The factors associated with utilities in the multivariate analysis were sex (beta =-0.084, 95% confidence interval [CI]: -0.154; -0.013 for females), number of exacerbations the previous year (-0.027, 95% CI: -0.044; -0.010), and modified Medical Research Council Dyspnea Scale (mMRC) score (-0.123 [95% CI: -0.185; -0.061], -0.231 [95% CI: -0.301; -0.161], and -0.559 [95% CI: -0.660; -0.458] for mMRC scores 2, 3, and 4 versus 1), all P<0.05. CONCLUSION: Multivariate analysis showed that female sex, frequent exacerbations, and an increased level of dyspnea were the main factors associated with reduced utility values in patients with COPD.

Generic utilities in chronic obstructive pulmonary disease patients stratified according to different staging systems.

BACKGROUND: To determine generic utilities for Spanish chronic obstructive pulmonary disease (COPD) patients stratified by different classifications: GOLD 2007, GOLD 2013, GesEPOC 2012 and BODEx index. METHODS: Multicentre, observational, cross-sectional study. Patients were aged ≥40 years, with spirometrically confirmed COPD. Utility values were derived from EQ-5D-3 L. Means, standard deviations (SD), medians and interquartile ranges (IQR) were computed based on the different classifications. Differences in median utilities between groups were assessed by non-parametric tests. RESULTS: 346 patients were included, of which 85.5% were male with a mean age of 67.9 (SD = 9.7) years and a mean duration of COPD of 7.6 (SD = 5.8) years; 80.3% were ex-smokers and the mean smoking history was 54.2 (SD = 33.2) pack-years. Median utilities (IQR) by GOLD 2007 were 0.87 (0.22) for moderate; 0.80 (0.26) for severe and 0.67 (0.42) for very-severe patients (p < 0.001 for all comparisons). Median utilities by GOLD 2013 were group A: 1.0 (0.09); group B: 0.87 (0.13); group C: 1.0 (0.16); group D: 0.74 (0.29); comparisons were statistically significant (p < 0.001) except A vs C. Median utilities by GesEPOC phenotypes were 0.84 (0.33) for non exacerbator; 0.80 (0.26) for COPD-asthma overlap; 0.71 (0.62) for exacerbator with emphysema; 0.72 (0.57) for exacerbator with chronic bronchitis (p < 0.001). Comparisons between patients with or without exacerbations and between patients with COPD-asthma overlap and exacerbator with chronic bronchitis were statistically-significant (p < 0.001). Median utilities by BODEx index were: group 0-2: 0.89 (0.20); group 3-4: 0.80 (0.27); group 5-6: 0.67 (0.29); group 7-9: 0.41 (0.31). All comparisons were significant (p < 0.001) except between groups 3-4 and 5-6. CONCLUSION: Irrespective of the classification used utilities were associated to disease severity. Some clinical phenotypes were associated with worse utilities, probably related to a higher frequency of exacerbations. GOLD 2007 guidelines and BODEx index better discriminated patients with a worse health status than GOLD 2013 guidelines, while GOLD 2013 guidelines were better able to identify a smaller group of patients with the best health.

Cost-effectiveness and harm-benefit analyses of risk-based screening strategies for breast cancer.

The one-size-fits-all paradigm in organized screening of breast cancer is shifting towards a personalized approach. The present study has two objectives: 1) To perform an economic evaluation and to assess the harm-benefit ratios of screening strategies that vary in their intensity and interval ages based on breast cancer risk; and 2) To estimate the gain in terms of cost and harm reductions using risk-based screening with respect to the usual practice. We used a probabilistic model and input data from Spanish population registries and screening programs, as well as from clinical studies, to estimate the benefit, harm, and costs over time of 2,624 screening strategies, uniform or risk-based. We defined four risk groups, low, moderate-low, moderate-high and high, based on breast density, family history of breast cancer and personal history of breast biopsy. The risk-based strategies were obtained combining the exam periodicity (annual, biennial, triennial and quinquennial), the starting ages (40, 45 and 50 years) and the ending ages (69 and 74 years) in the four risk groups. Incremental cost-effectiveness and harm-benefit ratios were used to select the optimal strategies. Compared to risk-based strategies, the uniform ones result in a much lower benefit for a specific cost. Reductions close to 10% in costs and higher than 20% in false-positive results and overdiagnosed cases were obtained for risk-based strategies. Optimal screening is characterized by quinquennial or triennial periodicities for the low or moderate risk-groups and annual periodicity for the high-risk group. Risk-based strategies can reduce harm and costs. It is necessary to develop accurate measures of individual risk and to work on how to implement risk-based screening strategies.

An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain.

BACKGROUND: The aim of this study was to evaluate the calibration and discriminatory power of three predictive models of breast cancer risk. METHODS: We included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries. The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area under the receiver operating characteristic curve (AUC) and the Harrell's C statistic. RESULTS: The Gail and Chen models showed good calibration while the Barlow model overestimated the number of cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest discrimination, with an AUC around 0.58. The Harrell's C statistic showed very similar values in the 5-year projection for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the number of cases in some breast density categories. CONCLUSIONS: These models cannot be used as a measure of individual risk in early detection programs to customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint models of survival and longitudinal data may be a step towards personalized early detection of BC.

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia.

Adult T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic tumor associated with poor outcome. In this study, we analyzed the prognostic relevance of genetic alterations, immunophenotypic markers, and microarray gene expression signatures in a panel of 53 adult T-ALL patients treated in the Eastern Cooperative Oncology Group E2993 clinical trial. An early immature gene expression signature, the absence of bi-allelic TCRG deletion, CD13 surface expression, heterozygous deletions of the short arm of chromosome 17, and mutations in IDH1/IDH2 and DNMT3A genes are associated with poor prognosis in this series. In contrast, expression of CD8 or CD62L, homozygous deletion of CDKN2A/CDKN2B, NOTCH1 and/or FBXW7 mutations, and mutations or deletions in the BCL11B tumor suppressor gene were associated with improved overall survival. Importantly, the prognostic relevance of CD13 expression and homozygous CDKN2A/CDKN2B deletions was restricted to cortical and mature T-ALLs. Conversely, mutations in IDH1/IDH2 and DNMT3A were specifically associated with poor outcome in early immature adult T-ALLs. This trial was registered at www.clinicaltrials.gov as #NCT00002514.