Economic impact of managing invasive mold disease with isavuconazole compared with liposomal amphotericin B followed by posaconazole in Spain.

BACKGROUND: Invasive fungal infections (IFI) are associated with significant morbidity and mortality. The objective of this work was to compare the costs per adult patient, associated with intravenous isavuconazole (ISAV) followed by oral ISAV versus the regimen of liposomal amphotericin B followed by posaconazole (L-AMB→POSA) in the treatment of IFI. The comparison was conducted from the perspective of the Spanish National Health System (SNS). METHODS: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration, hospitalization, laboratory tests and adverse events costs were evaluated from SNS perspective. Deterministic and probabilistic sensitivity analyzes were performed. RESULTS: Total costs per-patient were €24,715.54 with ISAV versus €29,753.53 with L-AMB→POSA, resulting in cost-savings per patient treated with ISAV of €5,037.99 (-16.9%). Treatment costs of IFI remained lower for ISAV than for L-AMB→POSA across all sensitivity analyses (-7,968.89€ to -326.59€), being treatment duration the most influential parameter. CONCLUSION: According to the present model, the treatment of IFIs with ISAV would generate savings for the SNS compared to L-AMB→POSA. These savings are attributed to the shorter duration of IV treatment, reduced use of healthcare resources and lower costs associated with managing adverse effects when ISAV was employed.

Risk factors associated with mortality among elderly patients with COVID-19: Data from 55 intensive care units in Spain.

INTRODUCTION AND OBJECTIVES: Critically-ill elderly ICU patients with COVID-19 have poor outcomes. We aimed to compare the rates of in-hospital mortality between non-elderly and elderly critically-ill COVID-19 ventilated patients, as well as to analyze the characteristics, secondary outcomes and independent risk factors associated with in-hospital mortality of elderly ventilated patients. PATIENTS AND METHODS: We conducted a multicentre, observational cohort study including consecutive critically-ill patients admitted to 55 Spanish ICUs due to severe COVID-19 requiring mechanical ventilation (non-invasive respiratory support [NIRS; include non-invasive mechanical ventilation and high-flow nasal cannula] and invasive mechanical ventilation [IMV]) between February 2020 and October 2021. RESULTS: Out of 5,090 critically-ill ventilated patients, 1,525 (27%) were aged ≥70 years (554 [36%] received NIRS and 971 [64%] received IMV. In the elderly group, median age was 74 years (interquartile range 72-77) and 68% were male. Overall in-hospital mortality was 31% (23% in patients <70 years and 50% in those ≥70 years; p<0.001). In-hospital mortality in the group ≥70 years significantly varied according to the modality of ventilation (40% in NIRS vs. 55% in IMV group; p<0.001). Factors independently associated with in-hospital mortality in elderly ventilated patients were age (sHR 1.07 [95%CI 1.05-1.10], p<0.001); previous admission within the last 30 days (sHR 1.40 [95%CI 1.04-1.89], p = 0.027); chronic heart disease (sHR 1.21 [95%CI 1.01-1.44], p = 0.041); chronic renal failure (sHR 1.43 [95%CI 1.12- 1.82], p = 0.005); platelet count (sHR 0.98 [95% CI 0.98-0.99], p<0.001); IMV at ICU admission (sHR 1.41 [95% CI 1.16- 1.73], p<0.001); and systemic steroids (sHR 0.61 [95%CI 0.48- 0.77], p<0.001). CONCLUSIONS: Amongst critically-ill COVID-19 ventilated patients, those aged ≥70 years presented significantly higher rates of in-hospital mortality than younger patients. Increasing age, previous admission within the last 30 days, chronic heart disease, chronic renal failure, platelet count, IMV at ICU admission and systemic steroids (protective) all comprised independent factors for in-hospital mortality in elderly patients.

Time to decision in sepsis.

OBJECTIVE: This study aimed to identify the common barriers leading to delayed initial management, microbiological diagnosis, and appropriate empirical antimicrobial treatment in sepsis. METHODS: A cross-sectional study was performed by the application of a population-based survey. Four different surveys were designed, targeting the healthcare personnel located in main hospital areas [emergency department (SEMES); infectious diseases and clinical microbiology-microbiological diagnosis (SEIMC-M); intensive care and infectious diseases, (SEMICYUC-GTEIS); and infectious diseases and clinical microbiology-clinical diagnosis, (SEIMC-C)]. RESULTS: A total of 700 valid surveys were collected from June to November 2019: 380 (54.3%) of SEMES, 127 (18.1%) of SEIMC-M, 97 (13.9%) de SEMICYUC-GTEIS and 96 (13.7%) of SEIMC-C, in 270 hospitals of all levels of care. The qSOFA score was used as a screening tool. The most used biomarker was procalcitonin (n=92, 39.8%). The sepsis code was implemented in 157 of 235 participating centers (66.2%), particularly in tertiary level hospitals. The mean frequency of contaminated blood cultures was 8.9% (8.7). In 85 (78.7%) centers, positive results of blood cultures were available within the first 72 hours and were communicated to the treating physician effectively by phone or e-mail in 76 (81.7%) cases. The main reason for escalating treatment was clinical deterioration, and the reason for de-escalating antimicrobials was significantly different between the specialties. Quality indicators were not frequently monitored among the different participating centers. CONCLUSIONS: There are significant barriers that hinder adequate management processes in sepsis in Spanish hospitals.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

Current treatment of nosocomial pneumonia and ventilator-associated pneumonia.

Hospital-acquired pneumonia and ventilator-associated pneumonia are severe nosocomial infections leading to high morbidity and mortality. Broad-spectrum antibiotics with coverage against all likely pathogens are recommended by the international guidelines. Inappropriate empirical treatment is one of the most important prognostic factors. Knowledge of local epidemiology and continuous microbiological surveillance is crucial for improving clinical approaches to empirical antimicrobial treatment. The development of protocols and policies for training healthcare professionals on preventive strategies, such as the "Pneumonia Zero" project, and improved implementation of antimicrobial stewardship practices, will aid early de-escalation of antibiotics and prevent resistance.

Transforming a public university hospital and its area of influence into a comprehensive resource in response to the COVID-19 pandemic.

INTRODUCTION AND OBJECTIVES: The outbreak of COVID-19 has overwhelmed healthcare systems all over the world. The aim of this article is to describe the process of transforming the Vall d'Hebron University Hospital, the second largest hospital in Spain, into a COVID-19 centre coordinating response to the pandemic in its reference area. MATERIALS AND METHODS: The study draws on the experience of the authors in transforming the hospital into a comprehensive resource in response to the COVID-19 pandemic. The strategy is based on four central strategies: early planning, coordination of all healthcare agents in its reference area, definition of clear leadership roles, and the organisation of care based on multidisciplinary teams with minimal recruitment of new staff. RESULTS: The transformation strategy enabled the hospital to cope with the surge in patients without exceeding its capacity. During the response phases, which amounted to a period of 57 days, 3106 patients consulted the ER and 2054 were admitted, 346 of whom were treated at the ICU. To accommodate the number of adult COVID-19 patients, adult ICU availability was progressive increased by 371%, and ordinary beds increased by 240. A total of 671 staff members went on sick leave after testing positive for COVID-19. CONCLUSION: The transformation experience of the hospital provides insight into how effectively adapt the structures and functioning of large hospitals. The relevance of territorial coordination during the pandemic is stressed as an effective strategy that contributed coping the pandemic.

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria.

OBJECTIVE: Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation. METHODS: A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert's experience. RESULTS: A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. CONCLUSIONS: The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.

Una revisión de los programas de intervención grupal con víctimas de violencia de género / A review of group intervention programs with victims of gender violence

La violencia de género es un problema personal y social grave, con múltiples consecuencias para las mujeres maltratadas. Los estudios de intervención para ayudar a estas personas son escasos y desde aproximaciones diversas. Se ha realizado aquí una revisión sistemática de los tratamientos aplicados en grupo a mujeres que han sido objeto de violencia de género. Se han revisado las bases de datos de Scopus, Web of Science, Google Scholar, ResearchGate, además de literatura gris. Del total de trabajos se han seleccionado 34 de ellos que sí eran estudios con datos de efica-cia, agrupados por el tipo de intervención: terapias cognitivo-conductuales (22), terapias contextuales (4) y programas diversos (8). Los resultados muestran que las terapias cognitivo-conductuales son eficaces para reducir las conductas de ansiedad, estrés y trastorno de estrés postraumático, con distintos tamaños del efecto y seguimientos hasta 12 meses. Las terapias contextuales son prometedoras en este campo y permiten una aplicación adaptada a la persona. Las demás terapias muestran eficacia en algunos casos, aunque partan de teorías diferentes utilizan también técnicas de la terapia cognitivo-conductual. Se concluye sobre la necesidad de investigar los componentes específicos de las terapias, y realizar estudios con diseños de grupos aleatorizados (AU)~

Gender violence is a serious personal and social problem, with multiple consequences for abused women. Inter-vention studies to help these people, are scarce and from different approaches. We have carried out a systematic review of the treatments applied in groups to women who have been in gender violence. The data bases of Scopus, Web of Science, Google Scholar, Dialnet and grey literature were reviewed. From the papers found, 34 of them have been select because they were studies with data about efficacy, grouped by the type of intervention: cognitive-behavioural therapies (22), contextual therapies (4), and diverse programmes (8). The results showed that cognitive-behavioural therapies are effective in reducing anxiety, stress, and PTSD behaviours, with varying effect sized and follow-ups to 12 months. Contextual therapies are promising in this field and can be addressed in an individualized way. The other therapies sowed efficacy in some cases, although each is based on different theories, they also use techniques from cognitive-behavioural therapies. We concluded that there is a need for research on the specific components of the therapies, and more studies with randomized group designs (AU)

Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain.

OBJECTIVE: Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. METHODS: The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens. RESULTS: In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. CONCLUSIONS: Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.

Recommendations for antibiotic selection for severe nosocomial infections.

Severe infection and its evolution to sepsis are becoming more prevalent every day and are among the leading causes of critical illness and mortality. Proper management is crucial to improve prognosis. This document addresses three essential points that have a significant impact on this objective: a) early recognition of patients with sepsis criteria, b) identification of those patients who suffer from an infection and have a high risk of progressing to sepsis, and c) adequate selection and optimization of the initial antimicrobial treatment.

[A systematic review and expert's analysis of risk factors of infections in adults due to carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii in Spain]. / Revisión sistemática de la literatura y análisis de expertos sobre los factores de riesgo asociados a infecciones causadas por Pseudomonas aeruginosa o Acinetobacter baumannii resistentes a carbapenémicos en pacientes adultos en España.

OBJECTIVE: The aim of the study is to identify risk factors associated to infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) in adult patients through a systematic literature review, classify them according to their importance and provide recommendations by experts in the Spanish context. METHODS: We developed a systematic literature review to identify risk factors associated to CRPA or CRAB infections and they were evaluated and discussed by a multidisciplinary panel of experts. RESULTS: There were included 29 studies for P. aeruginosa and 23 for A. baumannii out of 593 identified through systematic literature review. We identified 38 risk factors for P. aeruginosa and 36 for A. baumannii. After risk factor evaluation by the panel of experts, results for CRPA were: 11 important, 10 slightly important and 15 unimportant risk factors; and for CRAB were: 9 important, 5 slightly important and 19 unimportant risk factors. For both pathogens, previous use of antibiotics and hospitalization were important risk factors. CONCLUSIONS: We could identify the main risk factors associated to CRPA and CRAB through literature review. There is a need for developing additional studies with higher levels of evidence to identify sooner and better infected patients through associated risk factors.

Management of Psoriasis During Preconception, Pregnancy, Postpartum, and Breastfeeding: A Consensus Statement. / Consenso sobre las actuaciones a seguir durante la edad fértil, el embarazo, el posparto y la lactancia en pacientes con psoriasis.

OBJECTIVE: To develop evidence- and experience-based recommendations for the management of psoriasis during preconception, pregnancy, postpartum, and breastfeeding. METHODS: The nominal group technique and the Delphi method were used. Fifteen experts (12 dermatologists, 2 of whom were appointed coordinators; 1 rheumatologist; and 2 gynecologists) were selected to form an expert panel. Following a systematic review of the literature on fertility, pregnancy, postpartum, and breastfeeding in women with psoriasis, the coordinators drew up a series of preliminary recommendations for discussion by the panel at a nominal group meeting. The experts defined the scope, sections, and intended users of the statement and prepared a final list of recommendations. Consensus was obtained using a Delphi process in which an additional 51 dermatologists rated their level of agreement with each recommendation on a scale of 1 (total disagreement) to 10 (total agreement). Consensus was defined by a score of 7 or higher assigned by at least 70% of participants. Level of evidence and strength of recommendation were reported using the Oxford Center for Evidence-Based Medicine categories. The final statement was approved by the expert panel. RESULTS: The resulting consensus statement includes 23 recommendations on preconception (fertility and contraception), pregnancy (planning, pharmacological management, and follow-up), and breastfeeding (management and follow-up). Consensus was achieved for all recommendations generated except one. CONCLUSIONS: These recommendations for the better management of psoriasis in women of childbearing age could improve outcomes and prognosis.

Early identification and optimal management of carbapenem-resistant Gram-negative infection.

BACKGROUND: Carbapenem resistance in Gram-negative bacteria is associated with severe infections in the hospital setting. No uniform screening policy or agreed set of criteria exists within the EU to inform treatment decisions for infections caused by carbapenem-resistant Gram-negative bacteria. AIM: To develop a range of consensus statements to survey experts in carbapenem resistance, to identify potential similarities and differences across the EU and across specialties. METHODS: The survey contained 43 statements, covering six key topics relating to carbapenem-resistant organisms: microbiological screening; diagnosis; infection control implementation; antibiotic stewardship; use of resources; and influencing policy. FINDINGS: In total, 136 survey responses were received (66% infectious disease specialists, 18% microbiologists, 11% intensive care specialists, 4% other/unknown) from France, Germany, Greece, Italy, Spain, and the UK. High, or very high, levels of agreement were seen for all 43 consensus statements, indicating good alignment concerning early identification and optimal management of infection due to carbapenem-resistant organisms. CONCLUSION: We offer the following recommendations: (1) screening is required when a patient may have been exposed to the healthcare system in countries/hospitals where carbapenem-resistant organisms are endemic; (2) rapid diagnostic tools should be available in every institution; (3) all institutions should have a specific policy for the control of carbapenem-resistant organisms, which is routinely audited; (4) clear strategies are required to define both appropriate and inappropriate use of carbapenems; (5) priority funding should be allocated to the management of infections due to carbapenem-resistant organisms; and (6) international co-operation is required to reduce country-to-country transmission of carbapenem-resistant organisms.