USE OF ISAVUCONAZOLE IN PATIENTS WITH COVID- 19 IN AN INTENSIVE CARE UNIT

Background and importance Isavuconazole is a new antifungal triazole authorised for invasive aspergillosis and mucormycosis. It is a therapeutic alternative to voriconazole and liposomal amphotericin B for invasive aspergillosis, and to liposomal amphotericin B in mucormycosis. Aim and objectives To analyse prescription characteristics of isavuconazole in patients with COVID-19 in an intensive care unit (ICU) as well as its effectiveness and safety. Material and methods A cross-sectional, observational study was conducted (June 2020-April 2021). Patients with COVID-19 in an ICU on treatment with isavuconazole were included. Electronic prescription program and clinical history were used to collect the following data: sex, age, comorbidities, coinfection with other pathogens in addition to SARS-CoV-2, type of therapy (empirical/targeted), duration and previous azole treatment (yes/no). Effectiveness was evaluated by symptoms resolution, reasons for treatment suspension and status (alive/death) 30 days after completion of treatment. Safety was assessed according to adverse events (AE). Results Thirty-three patients (54.5% men) with mean age of 61 (35-77) years were evaluated. Twenty-nine patients (87.9%) had comorbidities, the most frequent were: hypertension (19.1%), dyslipidaemia (12.8%), obesity (11.7%) and diabetes (8.5%). Thirty-two (96.9%) had coinfections, with a mean of 1.8 (SD 1.2) infections/patient. The most implicated pathogens were: Acinetobacter baumanii (18.8%), Candida albicans (11.6%) and Aspergillus fumigatus (8.7%). Twentythree patients (69.7%) received isavuconazole as empirical therapy and 10 (30.3%) as targeted. Mean duration of treatment was 12.3 (SD 7.5) days. Twenty-five (75.6%) patients had not previously received azole treatment, 7 (21.3%) had received voriconazole and 1 (3%) fluconazole. Symptoms resolution was observed in 12 (36.4%) cases. Seven patients (21.2%) discontinued treatment due to negative culture, 12 (36.4%) due to symptoms resolution and 14 (42.4%) due to death. At 30 days completion of treatment, 15 patients (45.5%) remained alive and 18 (54.5%) had died. AE were recorded in 6 cases (18.2%): liver disorders (n=4) and electrolytic alterations (n=2). Conclusion and relevance Most patients presented comorbidities and coinfections in addition to COVID-19. Effectiveness of isavuconazol was adequate in approximately one-third of patients, despite the high severity and clinical complexity. Approximately half the patients remained alive at 30 days following completion of treatment. Isavuconazol was well tolerated in most cases.

Home delivery and telepharmacy programme: satisfaction of patients

Background and importanceThe SARS-CoV-2 pandemic has generated new needs in outpatient care of the hospital pharmacy. Despite the current improvement in the pandemic situation, many of the implemented progress have been maintained. Telepharmacy and home delivery programmes avoid hospital visits for vulnerable patients (elderly, pluripathology, mobility problems).Aim and objectivesTo analyse the degree of satisfaction of patients included in a telepharmacy and home delivery programme.Material and methodsDescriptive retrospective study of patients included in a telepharmacy and home delivery programme between November 2020 and September 2021 was conducted. Electronic clinical history and prescription software Farmatools were used to record data: sex, age, pathology, locality, transport conditions of the medication and number of shipments per patient. A telephone survey was conducted, consisting of four questions about: satisfaction with telepharmacy programme (yes/no), adequate pharmaceutical telephone support (yes/no), medication delivery conditions (correct/incorrect) and global assessment (ranged 1–10). Comments and suggestions were also requested.ResultsFifty-six patients were included, 35 (63%) were women and 21 (37%) men. Mean age was 65 (37–90) years. The pathologies involved were: 11 (20%) infectious diseases, 10 (18%) respiratory, 9 (16%) rheumatic, 8 (14%) neurological, 7 (12%) renal, 5 (9%) haematological, 3 (5%) ophthalmological, 2 (4%) digestive and 1 (2%) allergic. A total of 456 medication shipments were delivered during the study period, with a mean of 8 (2–24) per patient. The shipments were distributed among 31 different localities in the same health area. The medication for 27 (48%) patients required refrigerated transport, and 29 (52%) required ambient temperature. All (100%) patients were satisfied with telepharmacy programme and reported an adequate pharmaceutical telephone support. Medication delivery conditions were considered correct to 54 (96%) patients and incorrect to 2 (4%). Mean global assessment score was 9.6 (8–10). Four (7%) patients suggested an improvement in delivery conditions.Conclusion and relevanceThe survey results indicated a high degree of satisfaction of the patients included in the telepharmacy and home delivery programme. Although this system of pharmaceutical care and distribution of medicines was implemented because of the pandemic, its subsequent maintenance has allowed vulnerable patients to benefit. Further measures could be implemented to improve delivery conditions.References and/or acknowledgementsConflict of interestNo conflict of interest

Use of cefiderocol for multidrug-resistant Acinetobacter baumannii in patients with SARS-CoV-2: two case reports

Background and importanceCefiderocol is a new siderophore cephalosporin for the treatment of multidrug-resistant Gram-negative pathogens such as Acinetobacter baumannii (AB).Aim and objectivesTo describe our clinical experience with cefiderocol use in two SARS-CoV-2 patients with ventilator-associated pneumonia (VAP) due to multidrug-resistant AB (MRAB).Material and methodsA descriptive retrospective study on cefiderocol therapy in two patients with MRAB was conducted until 31 Augsut 2021. The electronic medical record was used to collect data: comorbidities, baseline clinical context, treatment, and clinical evolution of patients.ResultsA 49-year-old man with hypertension, obesity and chronic renal insufficiency was diagnosed with SARS-CoV-2. He required orotracheal intubation (OI) and mechanical ventilation (MV). The patient presented VAP after 4 weeks in the intensive care unit (ICU). Panresistant AB was isolated from bronchoalveolar lavage (BAL) and was treated with cefepime, imipenem, tigecycline and nebulised colistin. Given his poor clinical improvement, cefiderocol 2 g/8 hours (14 days) was initiated. No renal dose adjustment was performed for cefiderocol. Clinical evolution was favourable. The patient remained afebrile and acute phase reactants (APR) decreased. Unfavourable evolution and increased APR were observed on the third day after treatment with cefiderocol, with presence of AB in BAL. The patient died of multiorgan dysfunction syndrome 8 days later.A 65-year-old man with hypertension, dyslipidaemia and diabetes was diagnosed with SARS-CoV-2. He required OI and MV. After 4 weeks in ICU, the patient presented VAP due to MRAB and coinfection with Mycoplasma pneumoniae. Tigecycline, nebulised colistin and ceftazidime/avibactam were used. A clinical worsening was observed and cefiderocol 2 g/8 hours (14 days) and amikacin (5 days) were started. The patient remained afebrile and APR slightly decreased after initiation of cefiderocol and amikacin treatments. BAL culture was negative, although AB colonisation persisted in pharynx. Tigecycline, piperacillin/tazobactam and nebulised colistin were administered. After 71 days in ICU, the patient was transferred to a hospital ward, where he remained for 98 days before discharge.Conclusion and relevanceThe use of cefiderocol led to a slight improvement in two patients with VAP caused by MRAB. One patient died due to multiorgan dysfunction syndrome after cefiderocol therapy, and the other case required subsequent antibiotherapy due to persistence of MRAB.References and/or acknowledgementsConflict of interestNo conflict of interest

Efficacy of early use of remdesivir: a systematic review of subgroup analysis.

OBJECTIVE: A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and could significantly influence the efficiency in healthcare systems. The objective is the methodological interpretation of subgroup analyzes according to starting of remdesivir treatment with respect to symptom onset of COVID-19. METHODS: A search in Pubmed® database was performed. Randomized clinical trials (RCTs) with subgroup analysis regarding early and late use of remdesivir were selected. All endpoints were assessed using two methodologies. First methodology considered statistical interaction, pre-specification, biological plausibility, and consistency of results. Second methodology was a validated tool with preliminary questions to discard subset analysis without relevant minimum conditions, and a checklist with recommendations for applicability. RESULTS: A total of 54 results were found and five RCTs were selected. According first methodology, consistent heterogeneity was only found in time to clinical improvement and better clinical status score at day 15 for patients with severe COVID-19 and <7 days of symptoms. About second methodology, these results about early use of remdesivir may be applied to clinical practice with caution. CONCLUSIONS: We developed a systematic search and application of an established methodology for interpretation of subgroup analysis about early use of remdesivir. Results in severe COVID-19 suggested that early use of remdesivir provides a greater benefit in <7 days of symptoms for time to clinical improvement and better clinical status score at day 15. Future studies could use 7-day cut-off of symptoms to evaluate remdesivir.

[Post-covid syndrome after icu admission. Parameters related to a better physical recovery after 4 months.]

OBJECTIVE: Post-COVID syndrome can impact against every sphere of daily live. The objective of this work was to detect the factors correlated with a better or worse physical recovery four months after hospital discharge from a hospitalization in ICU due to COVID-19. METHODS: Prospective descriptive study of 125 patients valued by the Rehabilitation Service during hospitalization in ICU, from March 12th to December 31st, 2020. Data from 76 patients was analysed with clinical follow up after 1, 2 and 4 months of hospital discharge. Variables on personal, hospitalary, functional symptoms/signals and physical recovery were analysed with mean +/- standard deviation, counting (percentage), T-student test and Fisher test. RESULTS: After one month, fatigue was observed in 60 (80%) patients and dyspnoea in 47 (62%). After two months, fatigue in 37 (55%), dyspnoea in 25 (33%), shoulder pain in 33 (43%), average QuickDASH was 22.7 (11.3-50), Sit-to-Stand Test in 30 seconds 11.5 (10-13) and 6-minute walk test 390 meters (326-445). In the fourth month, 25 (53%) had returned to work and had an average of the physical recovery of 79.1%+/-18.3%. There was no correlation between physical recovery >=75% and the first month data, but there certainly was a correlation between some second month variables, such as fatigue (p=0.001), dyspnoea (p=0.035), QuickDASH (p=0.001) and 6-minute walk test (p=0.021). CONCLUSIONS: Symptoms (fatigue and dyspnoea) and functional scales (QuickDASH and 6-minute walk test) after 2 months predict a better/worsen physical recovery after 4 months of hospital discharge.

Impact of COVID-19 pandemic in the relink-c strategy to search and retrieve lost-to follow-up hcv patients

Background: There are patients with Hepatitis C Virus (HCV) infection previously diagnosed and lost to follow-up (LTFU) in the health system. Strategies to identify and linkage to care are necessary to achieve HCV elimination. The aims were to evaluate the impact of COVID-19 pandemic on LTFU patients in searching and retrieving HCV-RNA+ve individuals susceptible to treatment (ReLink-C strategy) and perform a health economic evaluation. Methods: ReLink-C strategy was based on a retrospective search of the microbiology databases of Barcelona north health area (450,000 inhabitants), followed by medical records review to identify and retrieve LTFU of HCV-RNA+ve individuals. Candidates for contacting were called (5 times maximum) to offer them a medical visit, reevaluation and subsequent treatment with direct-acting antivirals (DAAs). The search was done into two periods (pre-COVID, Jan 2019 to Feb 2020 and COVID, Mar 2020 to Dic 2020) to assess the impact of COVID on LTFU patients. In the economic evaluation, the costs of ReLink-C strategy were calculated, and a Markov model was used to estimate lifetime cases of liver complications, liver-related mortality and costs associated, compared to non-intervention. Results: Overall (01/2019 to 12/2020), 1,415 HCV-RNA+ve individuals were detected, 774 were selected for retrieval and 158 candidates for contact (The Figure shows the flowchart). After 5 calls, 99 individuals were located and 47 agreed to a visit. Finally, 41 individuals attended the visit and 38 started and completed DAA treatment. During COVID period, a higher percentage of individuals were selected for retrieval (65 vs 51%) and a lower percentage were candidates for contact (6 vs 13%) and located (4 vs 8%) comparing to pre-COVID period. At the end, a similar percentage of cases started treatment. The cost of ReLink-C strategy was €23.830 (search and diagnosis). During lifetime horizon, for a cohort of 133 viremic patients (158 candidates to contact excluding 23 treated, 1 death and 1 spontaneous cure) (38 treated in ReLink-C vs not treated in non-intervention), ReLink-C avoided 10 cases of decompensated cirrhosis, 6 hepatocellular carcinomas and 1 liver transplant, saving €423,372 associated to their management;deaths were reduced by 26%. Conclusion: Relink-C strategy retrieved and treated a high number of LTFU patients and showed to be cost-effective. COVID had a relevant impact on the linkage to care and treatment of HCV patients.

The impact of COVID-19 in small and medium-sized communication enterprises in Spain

The pandemic caused by COVID-19 has taken a large number of small and medium-sized Spanish companies by surprise. However, these SMEs dedicated to communication have seen how the economic crisis has not only not affected in the same way as the rest of companies and self-employed, but they are getting ahead, in a large majority, with the great hope that the crisis will respect them in this 2021, despite the tough adjustments they have had to make before the majority reduction of income. The study has been carried out in SMEs and self-employed workers in the Community of Aragon, mainly, but a small sample of those in Madrid has also been studied, as they are representative of what is happening in Spain. The aim of this work is to find out what measures have been adopted by these companies to face and weather the global crisis. Through an e-Delphi methodology, the main conclusions obtained were the high degree of positivity in the face of the crisis detected in these companies;their efforts to move forward, despite the economic blow that the drop in income has meant for most of them;and the high degree of solidarity with the rest of society shown by these people.

Subgroup analysis about efficacy of early use of remdesivir in COVID-19

Background and importance A greater benefit was suggested with early treatment with remdesivir against COVID-19. Aim and objectives To develop a systematic review and methodological interpretation of subgroup analyses according to timing of use of remdesivir in COVID-19. Material and methods A bibliographic review in MEDLINE was conducted up to 10 October 2020. The 'Clinical Queries/ Narrow' tool was used with the search strategy: ((Therapy/ Narrow[filter]) AND (remdesivir AND COVID)). Randomised clinical trials (RCTs) with subset analysis about early and late use of remdesivir (≤10 vs >10 days from symptom onset, or ≤9 vs >9 days) were selected. The rest of the studies were excluded. All endpoints with subgroup analysis regarding timing of remdesivir use were assessed. Two methodologies were applied. The first considered statistical interaction among subsets, prespecification, biological plausibility and consistency of the subgroup analyses of similar RCTs.1 The second methodology was a validated tool with preliminary questions to discard subset analysis without minimal relevance, and a checklist.2 This checklist assigned a score related to a recommendation for applicability of subgroup analysis in clinical practice. Results 20 results were found after review;16 studies were excluded because they were not RCTs and 1 study had no efficacy evaluation of remdesivir. Therefore, three RCTs were selected. Endpoints considered were: time to clinical improvement, mortality, viral load, and clinical status at days 11 and 15. According to the first methodology, no statistical interaction was observed in the outcomes of the RCTs. Prespecification was established in time to clinical improvement, and clinical status at day 15 of an RCT. Biological plausibility was described in the subset analysis of each endpoint of the RCTs. No consistency of subgroup analyses were found. The second methodology discarded the applicability of the subset analysis through preliminary questions in two RCTs because of the absence of minimal relevance. For the third RCT, 'null' recommendation (score -3 points) of clinical applicability was reached for clinical status at day 11. Conclusion and relevance No differences were found between early and late use of remdesivir in COVID-19. We developed the first study with a systematic review and methodology about subgroup analysis of timing of use of remdesivir.