Characteristics, clinical benefit and reimbursement of new authorisations for oncohaematology drugs in Spain between 2017 and 2020. / Características, beneficio clínico y financiación de las nuevas autorizaciones de fármacos oncohematológicos en España entre 2017 y 2020.

OBJECTIVE: To describe the authorisations and funding resolutions for new onco-hematological drugs in Spain between 2017 and 2020, as well as the results of their main trials. METHODS: Observational, cross-sectional, descriptive study conducted between October and December 2022. Onco-hematology drugs approved by the European Medicines Agency between 2017 and 2020 were included, according to EFPIA patients W.A.I.T Indicator 2021 Survey. Authorisation information was obtained from the main study of the European Public Assessment Report (EPAR). Data were collected on medicines, their authorisation and main study, benefit shown, cost, and status and time to reimbursement. RESULTS: Forty-one new drugs authorised for 49 indications were identified. More than half (58.5%) were targeted therapies, and 61.2% were for the treatment of solid tumors (61.2%). Most had palliative intent (71.4%) and were indicated in relapsed or refractory disease (55.1%). Of the clinical trials, 57.1% were phase III and 63.3% were randomised. The primary endpoint was overall survival in 16.3%, increasing to 25.8% among randomised clinical trials. Regarding licensed drugs based on response rate, the median response rate was 56.4% (IQI 40.0-66.3). In those authorised on the basis of surrogate time-to-event endpoints, the median Hazard Ratio was 0.54 (IQI 0.38-0.57), and among those using overall survival was 0.71 (IQI 0.59-0.77). Globally, 22.4% had shown benefit in overall survival, with a median gain of 4 months (IQI 3.6-16.7). One third (33.3%) of the indications evaluable according to the European Society for Medical Oncology Magnitude of Clinical Benefit Scale showed substantial clinical benefit. Of the indications, 75.5% were funded, half (48.6%; 36.7% of the total) with restrictions. The median time to funding was 19.5 months (IQI 11.4-29.3). CONCLUSIONS: Most main clinical trials of new onco-haematology drugs approved in Spain used surrogate primary endpoint and, at the time of authorisation, few had shown to prolong overall survival. More than a third were uncontrolled clinical trials.

Deprescribing in older patients with advanced cancer referred to palliative care.

OBJECTIVES: This study aimed to explore the prevalence of potentially inappropriate medications (PIMs) in a cohort of older adults with advanced cancer referred to palliative care. Secondary objectives were to describe the categories of identified PIMs and assess risk factors associated with their presence in this population. METHODS: This retrospective, observational study evaluated patients with advanced cancer admitted to a tertiary university hospital in Madrid, Spain and referred to palliative care between 1 January 2020 and 30 June 2020. Demographic, clinical, and pharmacotherapeutic data were obtained from the electronic medical records and regional databases. PIMs were assessed using the Screening Tool of Older Persons Prescriptions in Frail adults (STOPPFrail) criteria, V1. RESULTS: Among 123 patients (median age 80 years (IQR 73.5-87), 64.2% male), 74% presented at least one PIM according to the STOPPFrail criteria. The most common categories of inappropriate medications were lipid-lowering therapies, proton pump inhibitors, calcium supplements, and oral antidiabetics. The number of chronic comedications was significantly associated with PIM presence. CONCLUSIONS: Our study found a high prevalence of PIM among a cohort of older adults with advanced cancer and short life expectancy. This underlines the need for a comprehensive medication review to optimise pharmacotherapy in this population.

Real-world effectiveness and factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia receiving remdesivir.

OBJECTIVES: Evidence on the effectiveness of remdesivir when used in real-life clinical practice is controversial. This study aims to analyse its effectiveness and the factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia who require supplemental low-flow oxygen and received remdesivir. METHODS: A retrospective cohort study was conducted at Ramón y Cajal University Hospital (Madrid, Spain) which included all patients treated with remdesivir in our institution during the second pandemic breakout in Spain, from August to November 2020. Treatment with remdesivir was limited to non-critically ill patients with COVID-19 pneumonia requiring low-flow supplemental oxygen, with a treatment duration of 5 days. RESULTS: A total of 1757 patients were admitted with COVID-19 pneumonia during the study period, of which 281 non-critically ill patients were treated with remdesivir and included in the analysis. Mortality at 28 days after initiation of treatment was 17.1%. The median (IQR) time to recovery was 9 days (6-15). 104 (37.0%) patients had complications during hospitalisation, with renal failure being the most frequent (31 patients; 36.5%). After adjustment for confounding factors, high-flow oxygen therapy was associated with increased 28-day mortality (HR 2.77; 95% CI 1.39 to 5.53; p=0.004) and decreased 28-day clinical improvement (HR 0.54; 95% CI 0.35 to 0.85; p=0.008). A significant difference in survival and clinical improvement was identified between patients treated with high and low-flow oxygen. CONCLUSION: The 28-day mortality rate in patients treated with remdesivir needing low-flow oxygen therapy was higher than that published in clinical trials. Age and increased oxygen therapy needed after the beginning of treatment were the main risk factors associated with mortality.

Optimisation of the quality of care for patients with severe asthma: ASfarMA project.

Severe asthma has an important impact on patients and healthcare resources. Recently, the new specific treatments have defined a new scenario in which person-focused care and specialist multidisciplinary teams are necessary. Our Severe Asthma Unit (SAU) started the ASfarMA project along with an external human-centered design company to understand patients' vision of their illness, treatment, and healthcare experience, and to define the ideal SAU by performing a core group session, in-depth semistructured interviews and co-creation workshop. Herein, a series of tips classified as either 'transformative solutions' or 'quick wins', according to a value versus effort matrix are presented. Successful implementation of the proposed solutions will be valuable for patients and healthcare professionals, optimising patient care and resources. These findings can also be helpful to other SAUs or other humanisation projects involving complex, chronic and multidisciplinary pathologies.

Safety and tolerability of inhaled antibiotics in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is typically treated with inhaled antibiotics in clinical practice. However, there is a striking lack of standardised procedures for the preparation of noncommercial solutions. We used biochemical parameters to analyse the safety and tolerability of inhaled antibiotics in patients with bronchiectasis, and determined potential associations between the inhaled antibiotics used and adherence to the medications and quality of life. METHODS: We conducted a literature review, biochemical testing, and a pilot study of patients admitted to our hospital with noncystic fibrosis bronchiectasis. The MEDLINE database was searched for studies involving inhaled antibiotics to treat bronchiectasis. We analysed the pH, osmolality, and sodium and chloride ion concentrations of the antibiotics used. The pilot study included patients receiving inhaled antibiotic treatment. Demographic data, adherence, and quality of life were recorded and assessed. We determined potential associations between the study variables. RESULTS: The literature review identified 429 articles: 106 included precise instructions for diluting antibiotics, and 18 reported data on the biochemical parameters analysed. Laboratory results showed that some antibiotic dilutions were outside the range of tolerability, especially those involving dry powders for intravenous infusion, which must be diluted for their inhalation. Adherence was good in more than 80% of the patients, and higher in men and older patients. Men reported better quality of life. No associations were found between the antibiotics used and the other variables. CONCLUSION: Regarding the biochemical parameters analysed, there is a lack of information on the tolerability and biochemical safety of noncommercial dilutions of inhaled antibiotics used to treat bronchiectasis.

Serum zinc and copper in people with COVID-19 and zinc supplementation in parenteral nutrition.

OBJECTIVES: Zinc and copper are important to protect cells from oxidative stress and to enhance immunity. An association between low zinc levels and the severity of acute respiratory distress syndrome has been shown for people with COVID-19. We aimed to study serum zinc and copper concentrations in people with severe COVID-19 and zinc supplementation in parenteral nutrition (PN). METHODS: Thirty-five people with COVID-19 in need of PN were studied in a retrospective design. Serum samples were collected at three time points: at the start of PN, between 3 and 7 d after, and at the end of PN. RESULTS: Participants were on PN for a mean of 14 d, with a mean (± SD) daily supplemental zinc of 14.8 ± 3.7 mg/d. Serum zinc increased during PN administration from 98.8 ± 22.8 to 114.1 ± 23.3 µg/dL (Wilks' λ = 0.751, F = 5.459, P = 0.009). Conversely, serum copper did not vary from baseline (107.9 ± 34.2 µg/dL) to the end of the study (104.5 ± 37.4 µg/dL, Wilks' λ = 0.919, F = 1.453, P = 0.248). Serum zinc within the first week after starting PN and at the end of PN inversely correlated with total hospital stay (r = -0.413, P = 0.014, and r = -0.386, P = 0.022, respectively). Participants in critical condition presented lower serum copper (z = 2.615, P = 0.007). Mortality was not associated with supplemental zinc or with serum zinc or copper concentrations at any time of the study (P > 0.1 for all analyses). CONCLUSIONS: Serum zinc concentrations during PN support were inversely associated with length of hospital stay but not with mortality. Serum copper concentrations were lower in participants in critical condition but not associated with prognosis.