The Role of Multidimensional Prognostic Index to Identify Hospitalized Older Adults with COVID-19 Who Can Benefit from Remdesivir Treatment: An Observational, Prospective, Multicenter Study

Background: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. Objective: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from the use of remdesivir. Methods: This was a multicenter, prospective study of older adults hospitalized for COVID-19 in 10 European hospitals, followed-up for 90 days after hospital discharge. A standardized CGA was performed at hospital admission and the MPI was calculated, with a final score ranging between 0 (lowest mortality risk) and 1 (highest mortality risk). We assessed survival with Cox regression, and the impact of remdesivir on mortality (overall and in hospital) with propensity score analysis, stratified by MPI = 0.50. Results: Among 496 older adults hospitalized for COVID-19 (mean age 80 years, female 59.9%), 140 (28.2% of patients) were treated with remdesivir. During the 90 days of follow-up, 175 deaths were reported, 115 in hospital. Remdesivir treatment significantly reduced the risk of overall mortality (hazard ratio [HR] 0.54, 95% confidence interval CI 0.35–0.83 in the propensity score analysis) in the sample as whole. Stratifying the population, based on MPI score, the effect was observed only in less frail participants (HR 0.47, 95% CI 0.22–0.96 in propensity score analysis), but not in frailer subjects. In-hospital mortality was not influenced by remdesivir use. Conclusions: MPI could help to identify less frail older adults hospitalized for COVID-19 who could benefit more from remdesivir treatment in terms of long-term survival

Effects of oral amino acid supplementation on multidimensional prognostic index in hospitalized older patients: A multicenter randomized, double-blind, placebo-controlled pilot study

Background: It is not known whether amino acid supplementations may influence health status in hospitalized older acutely ill patients. Aim: The aim of this study was to determine whether nutritional supplementation with amino acids (Aminoglutam®) is associated with multidimensional improvement assessed with the Multidimensional Prognostic Index (MPI). Methods: In this randomized, double-blind, placebo-controlled pilot clinical trial, 126 patients aged ≥65 years were enrolled from 6 Italian geriatric wards. A multidimensional assessment to calculate the MPI was performed at baseline and after 4 weeks of treatment with nutritional supplementation (96 kcal, 12 g amino acids, 0.18 g fat, 11.6 g carbohydrate, and vitamins B1, B6, and C) or placebo administered twice a day. Logistic regression modeling was applied to determine the effect of treatment on the improvement of MPI (vs no-change/worsening), adjusting for gender, age, and MPI at baseline. Treatment’s interactions with age, gender, and MPI at baseline were tested adding the appropriate interaction parameter in the regression models. Results: Of the 126 patients included, 117 patients (93%) completed the study. A significant improvement in the MPI score was detected in the overall population (mean difference post-pretreatment: −0.03, p=0.001), with no differences between active and placebo arms. Men in the amino acid supplementation group had a significantly higher rate of improvement in MPI (81%) compared to the placebo group (46%) (Fisher’s exact test p=0.03). Adjusting for age, diagnosis, and MPI at baseline, amino acid treatment was shown to be associated with an improvement in MPI in men (OR=4.82, 95% confidence interval [CI]: 0.87–26.7) and not in women (OR=0.70, 95% CI: 0.27–1.81). The interaction effect between active treatment and gender was significant (p=0.04). Conclusion: A 4-week amino acid supplementation improved the MPI significantly in hospitalized older male patients but not in female patients. Further studies are needed to confirm the gender effect of amino acid supplementation on MPI in older patients

Testing of microbial contamination during the preparation of the radiocompound [90Y]DOTATOC for clinical trials: A process validation study by media fill approach

Aim. Radioisotopes used in nuclear radiopharmacy possess short half-lives, not allowing enough time to wait for completion of sterility tests. Moreover, carrying out sterility tests on highly radioactive solutions inside the hospital microbiology laboratory arises concerns about radioprotection. Therefore, the release of radiopharmaceuticals for injection is allowed in microbial analysis. For this reason, the effectiveness of the aseptic procedures has to be continuously assessed in order to guarantee the safety of the drug. The aim of this study was to validate the sterile preparation of [90Y]DOTATOC by means of media fill test. Methods. In order to validate the process, a simulation test was used: the media fill test. To apply this method, operators simulated each step of the process using culture medium (Triptic Soy Broth, TSB) instead of actual radiopharmaceutical product. Media fill test procedure has been subdivided into 5 phases, from the simulation of reagent preparation through the dispensing operations up to ward delivery. After every step, the processed medium was incubated at 35°C for 14 days. If the compounding procedures are adequately performed, no growth of microorganisms will be detected. Results. Microbiological analyses, carried out on all vials obtained at the end of each step, showed no microbial growth. For this reason, sterility tests were considered satisfactory. Conclusion. Application of media-fill test allowed both to validate operative modality used for [90Y]-DOTATOC handling and to attest the ability of operators who worked on it. Additionally, a correct quality control of the radiopharmaceutical i.v. preparations allows clinic infections control and prevention

Effects of oral amino acid supplementation on Multidimensional Prognostic Index in hospitalized older patients: a multicenter randomized, double-blind, placebo-controlled pilot study

Stefano Volpato,1 Romina Custureri,2 Matteo Puntoni,3 Lara Bianchi,1 Julia Daragjati,4 Sara Garaboldi,2 Matteo Simonato,4 Antonio Greco,5 Emanuele Rizzo,6 Pierluigi Dal Santo,7 Antonio Mangiacotti,5 Ekaterini Zigoura,2 Giacomo Siri,3 Alberto Pilotto2 1Department of Medical Science, University of Ferrara, Ferrara, Italy; 2Department of Geriatric Care, Orthogeriatrics and Rehabilitation, E.O. Galliera Hospital, Genova, Italy; 3Clinical Trial Unit, Scientific Directorate, E.O. Galliera Hospital, Genoa, Italy; 4Geriatrics Unit, San Antonio Hospital, ULSS 6 Euganea, Padova, Italy; 5Geriatrics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy; 6Geriatrics Unit, ULSS 2 Marca Trevigiana, Montebelluna, Italy; 7Geriatrics Unit, ULSS 5 Polesana, Rovigo, Italy Background: It is not known whether amino acid supplementations may influence health status in hospitalized older acutely ill patients. Aim: The aim of this study was to determine whether nutritional supplementation with amino acids (Aminoglutam®) is associated with multidimensional improvement assessed with the Multidimensional Prognostic Index (MPI). Methods: In this randomized, double-blind, placebo-controlled pilot clinical trial, 126 patients aged ≥65 years were enrolled from 6 Italian geriatric wards. A multidimensional assessment to calculate the MPI was performed at baseline and after 4 weeks of treatment with nutritional supplementation (96 kcal, 12 g amino acids, 0.18 g fat, 11.6 g carbohydrate, and vitamins B1, B6, and C) or placebo administered twice a day. Logistic regression modeling was applied to determine the effect of treatment on the improvement of MPI (vs no-change/worsening), adjusting for gender, age, and MPI at baseline. Treatment’s interactions with age, gender, and MPI at baseline were tested adding the appropriate interaction parameter in the regression models. Results: Of the 126 patients included, 117 patients (93%) completed the study. A significant improvement in the MPI score was detected in the overall population (mean difference post-pretreatment: -0.03, p=0.001), with no differences between active and placebo arms. Men in the amino acid supplementation group had a significantly higher rate of improvement in MPI (81%) compared to the placebo group (46%) (Fisher’s exact test p=0.03). Adjusting for age, diagnosis, and MPI at baseline, amino acid treatment was shown to be associated with an improvement in MPI in men (OR=4.82, 95% confidence interval [CI]: 0.87–26.7) and not in women (OR=0.70, 95% CI: 0.27–1.81). The interaction effect between active treatment and gender was significant (p=0.04). Conclusion: A 4-week amino acid supplementation improved the MPI significantly in hospitalized older male patients but not in female patients. Further studies are needed to confirm the gender effect of amino acid supplementation on MPI in older patients. Keywords: Multidimensional Prognostic Index, aging, hospitalization, oral supplementation, amino acid

Case Report: Two Cases of Pediatric Thrombotic Thrombocytopenic Purpura Treated With Combined Therapy

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. Over 95% of TTPs are acquired, due to autoantibody inhibitors. In children, acquired TTP is a very rare, life-threatening disease. To date, no consensus exists on the treatment strategy of pediatric TTP. We report the cases of two pediatric patients with a diagnosis of TTP, successfully treated with a combination of various therapeutic approaches. Although the patients complained of different sets of symptoms, laboratory data showed Coombs negative hemolytic anemia, renal impairment, and low platelet count in both cases. The diagnosis of acquired TTP was supported by the PLASMIC score and confirmed by the reduction of the ADAMTS13 activity and the presence of anti-ADAMTS13 antibodies. Intravenous immunoglobulin, corticosteroids, and plasma exchange (PEX) were performed without delay. As soon as available, caplacizumab was added to the therapy, with a prompt normalization of platelet count. Nevertheless, ADAMTS13 activity was persistently low, and anti-ADAMTS13 antibodies level was high; thus, a course of rituximab was administered, with persistent normalization of laboratory findings. No adverse events were observed during the treatment. In our experience, the combined use of PEX, caplacizumab, and immunosuppressive therapy during the acute phase of the disease is safe and may have a significant impact on the prognosis with successful clinical outcome and decrease in life-threatening events

Multidimensional prognostic index (MPI) predicts non-invasive ventilation failure in older adults with acute respiratory failure

Background: Acute respiratory failure (ARF) is a very common complication among hospitalized older adults. Non-invasive ventilation (NIV) may avoid admission to intensive care units, intubation and their related complication, but still lacks specific indications in older adults. Multidimensional Prognostic Index (MPI) based on comprehensive geriatric assessment (CGA) could have a role in defining the short-term prognosis and the best candidates for NIV among older adults with ARF. Methods: This is a retrospective observational study which enrolled patients older than 70 years, consecutively admitted to an acute geriatric unit with ARF. A standardized CGA was used to calculate the MPI at admission. Multivariate Cox regression models were used to test if MPI score could predict in-hospital mortality and NIV failure. Receiver operator curve (ROC) analysis was used to identify the discriminatory power of MPI for NIV failure. Results: We enrolled 231 patients (88.2 ± 5.9 years, 47% females). Mean MPI at admission was 0.76±0.16. In-hospital mortality rate was 33.8%, with similar incidence in patients treated with and without NIV. Among NIV users (26.4%), NIV failure occurred in 39.3%. Higher MPI scores at admission significantly predicted in-hospital mortality (β=4.46, p<0.0001) among patients with ARF and NIV failure (β=7.82, p = 0.001) among NIV users. MPI showed good discriminatory power for NIV failure (area under the curve: 0.72, 95% CI: 0.58–0.85, p<0.001) with optimal cut-off at MPI value of 0.84. Conclusions: MPI at admission might be a useful tool to early detect patients more at risk of in-hospital death and NIV failure among older adults with ARF

Can the Multidimensional Prognostic Index Improve the Identification of Older Hospitalized Patients with COVID-19 Likely to Benefit from Mechanical Ventilation? An Observational, Prospective, Multicenter Study

Objective: Data on prognostic tools for indicating mechanical ventilation in older people with COVID-19 are still limited. The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from mechanical ventilation. Design: Longitudinal, multicenter study. Settings and Participants: 502 older people hospitalized for COVID-19 in 10 European hospitals. Methods: MPI was calculated using 8 different domains typical of the CGA. A propensity score, Cox's regression analysis was used for assessing the impact of mechanical ventilation on rehospitalization/mortality for 90 days' follow-up, stratified by MPI = 0.50. The accuracy of MPI in predicting negative outcomes (ie, rehospitalization/mortality) was assessed using the area under the curve (AUC), and the discrimination with several indexes like the Net Reclassification Improvement (NRI) and the Integrated Discrimination Improvement (IDI). Results: Among 502 older people hospitalized for COVID-19 (mean age: 80 years), 152 were treated with mechanical ventilation. In the propensity score analysis, during the 90-day follow-up period, there were 44 rehospitalizations and 95 deaths. Mechanical ventilation in patients with MPI values ≥ 0.50, indicating frailer participants, was associated with a higher risk of rehospitalization/mortality (hazard ratio 1.56, 95% CI 1.09-2.23), whereas in participants with MPI values < 0.50 this association was not significant. The accuracy of the model including age, sex, respiratory parameters, and MPI was good (AUC = 0.783) as confirmed by an NRI of 0.2756 (P < .001) and an IDI of 0.1858 (P < .001), suggesting a good discrimination of the model in predicting negative outcomes. Conclusions and Implications: MPI could be useful for better individualizing older people hospitalized by COVID-19 who could benefit from mechanical ventilation