Nuova ricerca

ALESSIA VERDURI

CULTORE DELLA MATERIA
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

Home |


Pubblicazioni

2024 - Impact of frailty on symptom burden in Chronic Obstructive Pulmonary Disease [Articolo su rivista]
Verduri, Alessia; Clini, Enrico; Carter, Ben; Hewitt, Jonathan
abstract

Chronic Obstructive Pulmonary Disease (COPD), the sixth leading cause of death in the United States in 2022 and the third leading cause of death in England and Wales in 2022, is associated with high symptom burden, particularly dyspnea. Frailty is a complex clinical syndrome associ-ated with an increased vulnerability to adverse health outcomes. The aim of this review was to explore the current evidence of the influence of frailty on symptoms in patients with a confirmed diagnosis of COPD according to GOLD guidelines. Fourteen studies report a positive association between frailty and symptoms, including dyspnea, assessed with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) scale. Data were analysed in a pooled a ran-dom-effects meta-analysis Mean Difference (MD). There was an association between COPD pa-tients living with frailty and increased score of CAT versus COPD patients without frailty [pooled SMD, 1.79 (95% CI 0.72-2.87); I2 =99%]. Lower association was found between frailty and dyspnea measured by mMRC scale versus COPD patients without frailty [pooled SMD, 1.91 (95% CI 1.15-2.66); I2 =98%]. The prevalence of frailty ranged from 8.8% to 82%, pre-frailty from 30.4% to 73.7% in people living with COPD. The available evidence supports the role of frailty in worsen-ing symptom burden in COPD patients living with frailty. The review shows that frailty is com-mon in patients with COPD. Future research is needed to have further details related to the data from CAT to improve our knowledge of the frailty impact in this population.

2023 - Frailty and its influence on mortality and morbidity in COPD: A systematic review and Meta-Analysis. [Articolo su rivista]
Verduri, Alessia; Carter, Ben; Laraman, James; Rice, Ceara; Clini, Enrico; Maskell, Nick; Hewitt., Jonathan
abstract

Background: Frailty increases vulnerability to adverse outcomes. Long-term conditions increase the risk of frailty. Methods: We searched PubMed, Web of Science, The Cochrane Library, EMBASE from inception to March 2022. Quality assessment was conducted using the NOS. Data was analysed in a pooled a random-effects meta-analysis. Our primary outcome was the impact of frailty on mortality in adults with Chronic Obstructive Pulmonary Disease (COPD) diagnosis according to the guidelines. Secondary outcomes were: frailty and association with readmissions, hospitalisations, exacerbation rates, and prevalence of frailty in COPD. Results: We identified 25 studies, with 5882 participants. The median prevalence of frailty was 47 (IQR, 39.3-66.3, range 6.4-72%). There was an association between COPD patients living with frailty and increased risk of mortality versus COPD patients without frailty (pooled OR,4.21 (95% CI 2.99-5.93, I2 55%). A descriptive analysis of relationship between frailty and hospital readmission and all cause hospitalization showed positive associations. The relationship between frailty and the risk of exacerbation showed a pooled OR, 1.45 (95% CI 0.37-5.70, I2 80%). Conclusion: Frailty is significantly associated with higher mortality risk in COPD. Frailty is common in patients with COPD and its measurement should be considered in clinical practice to better characterise COPD.

2023 - Frailty prevalence and association with clinical outcomes in Interstitial Lung Disease, Asthma, and Pleural Disease. [Articolo su rivista]
Verduri, Alessia; Carter, Ben; Rice, Ceara; Laraman, Ames; Barton, Eleanor; Clini, Enrico; Maskell, Nick; Hewitt, Jonathan
abstract

Background: Frailty is a syndrome characterised by increase vulnerability to negative outcomes. Interstitial Lung Disease (ILD), asthma, and pleural disease are leading causes of morbidity and mortality. We aimed to investigate the prevalence and impact of frailty in adult patients with these diseases. Methods: We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, The Cochrane Library, and EMBASE for studies reporting on frailty in ILD, asthma, and pleural disease. MeSH terms including Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis, Non-specific Interstitial Pneumonia, Chronic Hypersensitivity Pneumonitis, Systemic sclerosis-associated ILD, Connective tissue disease-associated ILD, and frailty were used as key words. The primary outcome was prevalence of frailty. Where enough data allowed a pooled random-effects meta-analysis was performed with mortality and hospitalisation as the outcomes. Results: We identified 6 relevant studies incorporating 1471 ILD patients (age 68.3±SD2.38; 50% male), which were either cohort or cross-sectional design rated either good or fair. The median prevalence of frailty was 48% (IQR25-50). There was a positive association between frail ILD patients and increased risk of long-term mortality (pooled OR, 2.33 95%CI 1.31-4.15, I2 9%). One study reported a hospitalization rate of HR=1.97(1.32-3.06) within 6 months in frail ILD patients. We identified 3 studies on frailty in asthma and no studies in pleural disease. The median prevalence in asthma was 9.5% (IQR7.8-11.3). Conclusions: Frailty is very common and associated with increased mortality in patients with ILD. There are still minimal data regarding the prevalence of frailty and its influence on the risk in this population. The review found three studies relating to frailty in asthma, which did not examine its impact on outcomes. No studies relating to pleural disease and frailty were identified.

2023 - Prevalence of asthma and COPD in a cohort of patients at the follow up after COVID-19 pneumonia. [Articolo su rivista]
Verduri, Alessia; Hewitt, Jonathan; Carter, Ben; Tonelli, Roberto; Clini, Enrico; Beghè, Bianca
abstract

Not available

2023 - Quality of life and intrinsic capacity in patients with post-acute COVID-19 syndrome is in relation to frailty and resilience phenotypes. [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Barbieri, Sara; Marchio', Tommaso; Caselgrandi, Agnese; Motta, Federico; Beghe', Bianca; Verduri, Alessia; Belli, Michela; Gozzi, Licia; Iadisernia, Vittorio; Faltoni, Matteo; Burastero, Giulia; Dessilani, Andrea; DEL MONTE, Martina; Dolci, Giovanni; Bacca, Erica; Franceschi, Giacomo; Yaacoub, Dina; Volpi, Sara; Mazzochi, Alice; Clini, Enrico; Mussini, Cristina
abstract

Background- The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). Methods- This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: “fit/resilient”, “fit/non-resilient”, “frail/resilient” and “frail/non-resilient”. Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. Results- 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Predictors for SF-36 score <61.60 were the phenotypes “frail/non-resilient” (OR=4.69, CI:2.08-10.55), “fit/non-resilient” (OR=2.79, CI:1.00-7.73). Predictors for EQ-5D-5L <89.7% were the phenotypes “frail/non-resilient” (OR=5.93, CI: 2.64-13.33) and “frail/resilient” (OR=5.66, CI:1.93-16.54). Predictors of impaired IC (below the mean score value) were “frail/non-resilient” (OR=7.39, CI:3.20-17.07), and “fit/non-resilient” (OR=4.34, CI:2.16-8.71) phenotypes. Conclusions- Resilience is complementary to frailty in the identification of clinical phenotypes with different impact on wellness and QoL. Frailty and resilience should be evaluated in hospitalized COVID-19 patients to identify vulnerable individuals to prioritize urgent health interventions in people with PACS.

2022 - Comparison between first and second wave of COVID-19 outbreak in older people: the COPE multicentre European observational cohort study [Articolo su rivista]
Verduri, A.; Short, R.; Carter, B.; Braude, P.; Vilches-Moraga, A.; Quinn, T. J.; Collins, J.; Lumsden, J.; Mccarthy, K.; Evans, L.; Myint, P. K.; Hewitt, J.; Clini, E.; Rickard, F.; Hesford, J.; Mitchell, E.; Hartrop, K.; Murphy, C.; Aggrey, K.; Bilan, J.; Quinn, T.; Kelly, J.; Murphy, C.; Moug, S.; Barlow-Pay, F. -.; Khan, A.; Espinoza, M. F. R.; Kneen, T.; Allafi, H.; Dafnis, A.; Vidal, M. N.; Price, A.; Pearce, L.; Einarsson, A.; Mccrorie, E. B.
abstract

Background: Effective shielding measures and virus mutations have progressively modified the disease between the waves, likewise healthcare systems have adapted to the outbreak. Our aim was to compare clinical outcomes for older people with COVID-19 in Wave 1 (W1) and Wave 2 (W2). Methods: All data, including the Clinical Frailty Scale (CFS), were collected for COVID-19 consecutive patients, aged ≥65, from 13 hospitals, in W1 (February-June 2020) and W2 (October 2020-March 2021). The primary outcome was mortality (time to mortality and 28-day mortality). Data were analysed with multilevel Cox proportional hazards, linear and logistic regression models, adjusted for wave baseline demographic and clinical characteristics. Results: Data from 611 people admitted in W2 were added to and compared with data collected during W1 (N = 1340). Patients admitted in W2 were of similar age, median (interquartile range), W2 = 79 (73-84); W1 = 80 (74-86); had a greater proportion of men (59.4% vs. 53.0%); had lower 28-day mortality (29.1% vs. 40.0%), compared to W1. For combined W1-W2 sample, W2 was independently associated with improved survival: time-to-mortality adjusted hazard ratio (aHR) = 0.78 [95% confidence interval (CI) 0.65-0.93], 28-day mortality adjusted odds ratio = 0.80 (95% CI 0.62-1.03). W2 was associated with increased length of hospital stay aHR = 0.69 (95% CI 0.59-0.81). Patients in W2 were less frail, CFS [adjusted mean difference (aMD) = -0.50, 95% CI -0.81, -0.18], as well as presented with lower C-reactive protein (aMD = -22.52, 95% CI -32.00, -13.04). Conclusions: COVID-19 older adults in W2 were less likely to die than during W1. Patients presented to hospital during W2 were less frail and with lower disease severity and less likely to have renal decline.

2022 - Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome. [Articolo su rivista]
Milic, J; Barbieri, S; Gozzi, L; Brigo, A; Beghe', B; Verduri, A; Bacca, E; Iadisernia, V; Cuomo, G; Dolci, G; Yaacoub, D; Aprile, E; Belli, M; Venuta, M; Meschiari, M; Sebastiani, G; Clini, E; Mussini, C; Lonardo, A; Guaraldi, G; Raggi, P.
abstract

Background: A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods: We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results: Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14-1.96), body mass index (OR = 1.14; 95% CI, 1.04-1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13-5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions: Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

2022 - Prognostic value of estimated glomerular filtration rate in hospitalised older patients (over 65) with COVID-19: a multicentre, European, observational cohort study. [Articolo su rivista]
Carter, B; Ramsay, Ea; Short, R; Goodison, S; Lumsden, J; Khan, A; Braude, P; Vilches-Moraga, A; Quinn, Tj; Mccarthy, K; Hewitt, J; Myint, Pk; Verduri, A; Clini, E; Cope, Study
abstract

Background: The reduced renal function has prognostic significance in COVID-19 and it has been linked to mortality in the general population. Reduced renal function is prevalent in older age and thus we set out to better understand its effect on mortality. Methods: Patient clinical and demographic data was taken from the COVID-19 in Older People (COPE) study during two periods (February-June 2020 and October 2020-March 2021, respectively). Kidney function on admission was measured using estimated glomerular filtration rate (eGFR). The primary outcomes were time to mortality and 28-day mortality. Secondary outcome was length of hospital stay. Data were analysed with multilevel Cox proportional hazards regression, and multilevel logistic regression and adjusted for individual patient clinical and demographic characteristics. Results: One thousand eight hundred two patients (55.0% male; median [IQR] 80 [73-86] years) were included in the study. 28-day mortality was 42.3% (n = 742). 48% (n = 801) had evidence of renal impairment on admission. Using a time-to-event analysis, reduced renal function was associated with increased in-hospital mortality (compared to eGFR ≥ 60 [Stage 1&2]): eGFR 45-59 [Stage 3a] aHR = 1.26 (95%CI 1.02-1.55); eGFR 30-44 [Stage 3b] aHR = 1.41 (95%CI 1.14-1.73); eGFR 1-29 [Stage 4&5] aHR = 1.42 (95%CI 1.13-1.80). In the co-primary outcome of 28-day mortality, mortality was associated with: Stage 3a adjusted odds ratio (aOR) = 1.18 (95%CI 0.88-1.58), Stage 3b aOR = 1.40 (95%CI 1.03-1.89); and Stage 4&5 aOR = 1.65 (95%CI 1.16-2.35). Conclusion: eGFR on admission is a good independent predictor of mortality in hospitalised older patients with COVID-19 population. We found evidence of a dose-response between reduced renal function and increased mortality.

2021 - Multiple House Occupancy is Associated with Mortality in Hospitalised Patients with Covid-19 [Articolo su rivista]
Bruce, Eilidh; Carter, Ben; Quinn, Terence J; Verduri, Alessia; Pearson, Oliver; Vilches-Moraga, Arturo; Price, Angeline; Mcgovern, Aine; Evans, Louis; Mccarthy, Kathryn; Hewitt, Jonathan; Moug, Susan; Myint, Phyo K; Behalf Of Cope Study Team, Null; Einarsson, Alice; Fleck, Anna; Bisset, Carly; Alexander, Ross; Guaraldi, Giovanni; Murphy, Caroline; Kelly, Joanna; Short, Roxanna; Braude, Philip; El Jichi Mutasem, Tarik; Singh, Sandeep; Paxton, Dolcie; Harris, Will; Hesford, James; Holloway, Mark; Mitchell, Emma; Rickard, Frances; Galbraith, Norman; Bhatti, Emma; Edwards, Jenny; Duffy, Siobhan; Barlow-Pay, Fenella; Pearce, Lyndsey; Garcia, Madeline; Sangani, Shefali; Kneen, Thomas; Lee, Thomas; Davey, Charlotte; Jones, Sheila; Lunstone, Kiah; Cavenagh, Alice; Silver, Charlotte; Telford, Thomas; Simmons, Rebecca; Stechman, Michael
abstract

In response to the COVID-19 pandemic, many countries mandated staying at home to reduce transmission. This study examined the association between living arrangements (house occupancy numbers) and outcomes in COVID-19.

2021 - Routine Use of Immunosuppressants is Associated with Mortality in Hospitalised Patients with Covid-19 [Articolo su rivista]
Myint, P; Carter, B; Barlow-Pay, Fa; Short, R; Einarsson, A; Bruce, E; Mccarthy, K; Verduri, A; Collins, J; Hesford, J; Rickard, F; Mitchell, E; Holloway, M; Mcgovern, A; Vilches-Moraga, A; Braude, P; Pearce, L; Stechman, M; Price, A; Quinn, T; Clini, E; Moug, S; Hewitt, J.
abstract

Background: Whilst there has been some literature on impact of SAR viruses in severely immunosuppressed, less is known about the link between general usage of immunosuppressants and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, carried out in ten UK and one Italian hospitals. Data were collected between 27th February and 28th April by trained data collectors and included all non-selected consecutive admissions with Covid-19. Type and dosage of immunosuppressant use were collected along with other covariate data. The primary outcome was the time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-7 mortality and the time-to-discharge (described as the length of stay). Data were analysed with a mixed-effects, Cox proportional hazards and Logistic regression models using non-users of immunosuppressants as the reference group. Results: 1184 patients were eligible to be included. The median (IQR) age was 74(63-81) and 676(58%) were male, and 299(25.3%) died in hospital. Most patients exhibited at least one comorbidity, and 113(~10%) were on immunosuppressants. We found that any immunosuppressant use was associated with increased mortality: aHR 1.89,95%CI:1.31,2.71 (time to mortality) and aOR 1.90,95%CI:1.16-3.10 (7-day mortality). There appeared to be a direct and linear dose-response relationship regardless of the agent used. Conclusion: Low threshold to seek medical advice and close monitoring of worsening symptoms should be exercised in those who take immunosuppressants regardless of their indication.

2020 - Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study [Articolo su rivista]
Vilches-Moraga, A.; Price, A.; Braude, P.; Pearce, L.; Short, R.; Verduri, A.; Stechman, M.; Collins, J. T.; Mitchell, E.; Einarsson, A. G.; Moug, S. J.; Quinn, T. J.; Stubbs, B.; McCarthy, K.; Myint, P. K.; Hewitt, J.; Carter, B.; Davey, C.; Jones, S.; Lunstone, K.; Cavenagh, A.; Evans, L.; Silver, C.; Telford, T.; Simmons, R.; Mutasem, T. E. J.; Singh, S.; Paxton, D.; Harris, W.; Galbraith, N.; Bhatti, E.; Edwards, J.; Duffy, S.; Kelly, J.; Murphy, C.; Bisset, C.; Alexander, R.; Garcia, M.; Sangani, S.; Kneen, T.; Lee, T.; Kyriakopoulos, G.; Thomas, M.; Tan, D.; Clini, E.; Bruce, E.; Rickard, F.; Balow-Pay, F.; Hesford, J.; Holloway, M.
abstract

Background: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. Methods: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. Results: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58–81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6–24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1–3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97–4.11); CFS 5, 3.77 (1.94–7.32); CFS 6, 4.04 (2.09–7.82); CFS 7, 2.16 (1.12–4.20); and CFS 8, 3.19 (1.06–9.56). Conclusions: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

2020 - Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople) [Articolo su rivista]
Carter, B.; Collins, J. T.; Barlow-Pay, F.; Rickard, F.; Bruce, E.; Verduri, A.; Quinn, T. J.; Mitchell, E.; Price, A.; Vilches-Moraga, A.; Stechman, M. J.; Short, R.; Einarsson, A.; Braude, P.; Moug, S.; Myint, P. K.; Hewitt, J.; Pearce, L.; Mccarthy, K.; Davey, C.; Jones, S.; Lunstone, K.; Cavenagh, A.; Silver, C.; Telford, T.; Simmons, R.; Holloway, M.; Hesford, J.; El Jichi Mutasem, T.; Singh, S.; Paxton, D.; Harris, W.; Galbraith, N.; Bhatti, E.; Edwards, J.; Duffy, S.; Kelly, J.; Murphy, C.; Bisset, C.; Alexander, R.; Garcia, M.; Sangani, S.; Kneen, T.; Lee, T.; Mcgovern, A.; Guaraldi, G.; Clini, E.
abstract

Background: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. Aim: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. Methods: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. Findings: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51–0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47–1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37–0.66). Conclusion: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

2020 - The influence of ACE inhibitors and ARBs on hospital length of stay and survival in people with COVID-19 [Articolo su rivista]
Philip Braude, P; Carter, B; Short, R; Vilches-Moraga, A; Verduri, A; Pearce, L; Price, A; Quinn, Tj; Stechman, M; Collins, J; Bruce, E; Einarsson, A; Rickard, F; Mitchell, E; Holloway, M; Hesford, J; Barlow-Pay, F; Clini, E; Myint, Pk; Moug, S; McCarthy, K; Hewitt, J.
abstract

Objective During the COVID-19 pandemic the continuation or cessation of angiotensin- converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) has been contentious. Mechanisms have been proposed for both beneficial and detrimental effects. Recent studies have focused on mortality with no literature having examined length of hospital stay. The aim of this study was to determine the influence of ACEi and ARBs on COVID-19 mortality and length of hospital stay. Methods COPE (COVID-19 in Older People) is a multicenter observational study including adults of all ages admitted with either laboratory or clinically confirmed COVID-19. Routinely generated hospital data were collected. Primary outcome: mortality; secondary outcomes: Day-7 mortality and length of hospital stay. A mixed-effects multivariable Cox’s proportional baseline hazards model and logistic equivalent were used. Results 1371 patients were included from eleven centres between 27th February to 25th April 2020. Median age was 74 years [IQR 61-83]. 28.6% of patients were taking an ACEi or ARB. There was no effect of ACEi or ARB on inpatient mortality (aHR=0.85, 95%CI 0.65-1.11). For those prescribed an ACEi or ARB, hospital stay was significantly reduced (aHR=1.25, 95%CI 1.02-1.54, p=0.03) and in those with hypertension the effect was stronger (aHR=1.39, 95%CI 1.09-1.77, p=0.007). Conclusions Patients and clinicians can be reassured that prescription of an ACEi or ARB at the time of COVID-19 diagnosis is not harmful. The benefit of prescription of an ACEi or ARB in reducing hospital stay is a new finding.

2018 - Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. [Articolo su rivista]
Schuetz, Philipp; Wirz, Yannick; Sager, Ramon; Christ-crain, Mirjam; Stolz, Daiana; Tamm, Michael; Bouadma, Lila; Luyt, Charles E.; Wolff, Michel; Chastre, Jean; Tubach, Florence; Kristoffersen, Kristina B.; Burkhardt, Olaf; Welte, Tobias; Schroeder, Stefan; Nobre, Vandack; Wei, Long; Bucher, Heiner C.; Annane, Djillali; Reinhart, Konrad; Falsey, Ann R.; Branche, Angela; Damas, Pierre; Nijsten, Maarten; De Lange, Dylan W.; Deliberato, Rodrigo O.; Oliveira, Carolina F.; Maravić-stojković, Vera; Verduri, Alessia; Beghe', Bianca; Cao, Bin; Shehabi, Yahya; Jensen, Jens-ulrik S.; Corti, Caspar; Van Oers, Jos A. H.; Beishuizen, Albertus; Girbes, Armand R. J.; De Jong, Evelien; Briel, Matthias; Muelle, Beat
abstract

BACKGROUND: In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. METHODS: Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. FINDINGS: We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (pinteractions>0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). INTERPRETATION: Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance.

2018 - Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials [Articolo su rivista]
Schuetz, P.; Bolliger, R.; Merker, M.; Christ-Crain, M.; Stolz, D.; Tamm, M.; Luyt, C. E.; Wolff, M.; Schroeder, S.; Nobre, V.; Reinhart, K.; Branche, A.; Damas, P.; Nijsten, M.; Deliberato, R. O.; Verduri, A.; Beghe', B.; Cao, B.; Shehabi, Y.; Jensen, J. -U. S.; Beishuizen, A.; de Jong, E.; Briel, M.; Welte, T.; Mueller, B.
abstract

Introduction: Although evidence indicates that use of procalcitonin to guide antibiotic decisions for the treatment of acute respiratory infections (ARI) decreases antibiotic consumption and improves clinical outcomes, algorithms used within studies had differences in PCT cut-off points and frequency of testing. We therefore analyzed studies evaluating procalcitonin-guided antibiotic therapy and propose consensus algorithms for different respiratory infection types. Areas covered: We systematically searched randomized-controlled trials (search strategy updated on February 2018) on procalcitonin-guided antibiotic therapy of ARI in adults using a pre-specified Cochrane protocol and analyzed algorithms from 32 trials that included 10,285 patients treated in primary care settings, emergency departments (ED), and intensive care units (ICU). We derived consensus algorithms for use of procalcitonin by the type of ARI including community-acquired pneumonia, bronchitis, chronic obstructive pulmonary disease or asthma exacerbation, sepsis, and post-operative sepsis due to respiratory infection. Consensus algorithm recommendations differ with regard to timing of treatment (i.e. timing of initiation in low-risk patients or discontinuation in high-risk patients) and procalcitonin cut-off points for the recommendation/strong recommendation to discontinue antibiotics (≤ 0.25/≤ 0.1 µg/L in ED and inpatients, ≤ 0.5/≤ 0.25 µg/L in ICU patients, and reduction by ≥ 80% from peak levels in sepsis patients). Expert commentary: Our proposed algorithms may facilitate safe and efficient implementation of procalcitonin-guided antibiotic protocols in diverse healthcare settings. Still, the decision about initiation and cessation of antibiotic treatment remains a clinical decision based on the patient assessment and the severity of illness and use of procalcitonin should not delay empirical treatment in high risk situations.

2017 - Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. [Articolo su rivista]
Schuetz, P; Wirz, Y; Sager, R; Christ-crain, M; Stolz, D; Tamm, M; Bouadma, L; Luyt, Ce; Wolff, M; Chastre, J; Tubach, F; Kristoffersen, Kb; Burkhardt, O; Welte, T; Schroeder, S; Nobre, V; Wei, Licheng; Bucher, Hc; Bhatnagar, N; Annane, D; Reinhart, K; Branche, A; Damas, P; Nijsten, M; De Lange, Dw; Deliberato, Ro; Lima, Ss; Maravić-stojković, V; Verduri, A; Cao, B; Shehabi, Y; Beishuizen, A; Jensen, Js; Corti, C; Van Oers, Ja; Falsey, Ar; De Jong, E; Oliveira, Cf; Beghe, B; Briel, M; Mueller, B.
abstract

BACKGROUND:Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. OBJECTIVES:The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. SELECTION CRITERIA: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS:Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis.MAIN RESULTS:From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidanc

2015 - Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin: A randomized noninferiority trial [Articolo su rivista]
Verduri, Alessia; Luppi, Fabrizio; D'Amico, Roberto; Balduzzi, Sara; Vicini, Roberto; Liverani, Anna; Ruggieri, Valentina; Plebani, Mario; Barbaro Foschino, Maria Pia; Spanevello, Antonio; Canonica, Giorgio Walter; Papi, Alberto; Fabbri, Leonardo; Beghe', Bianca
abstract

The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD. METHODS AND FINDINGS: We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days. CONCLUSIONS: Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098). TRIAL REGISTRATION: ClinicalTrials.gov NCT01125098.

2014 - Poor adherence to guidelines for long-term oxygen therapy (LTOT) in two Italian university hospitals. [Articolo su rivista]
Verduri, Alessia; L., Ballerin; M., Simoni; M., Cellini; E., Vagnoni; P., Roversi; A., Papi; Clini, Enrico; Fabbri, Leonardo; A., Potena
abstract

Long-term oxygen therapy (LTOT) improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. Adherence to LTOT guidelines is problematic, both because efficacy has been demonstrated only in specific groups of COPD patients, and because it implies high costs. Introduces treatment high costs. The aim of our study was to examine retrospectively the adherence to LTOT guidelines in a sample of medical records of patients prescribed LTOT between January 2005 and December 2006 in two Italian university hospitals (Ferrara and Modena). Out of a total of 191 medical records of patients prescribed LTOT, only 157 had adequate clinical data considering the three main criteria for appropriateness (arterial blood gas and/or pulse oximetry measurement, oxygen administration, smoking status). Out of these 157 patients, only 73 (46.5 %) fulfilled all three criteria recommended by the guidelines. Adherence was higher for LTOT prescribed by pulmonologists compared to internists. This survey showed that the adherence to LTOT guidelines in a sample of medical records of patients prescribed LTOT is poor. Considering the high costs and the impact on the patients' quality of life of LTOT, these results suggest that the adherence should be carefully monitored.

2013 - Echocardiography, Spirometry, and Systemic Acute-Phase Inflammatory Proteins in Smokers with COPD or CHF: An Observational Study [Articolo su rivista]
Beghe', Bianca; Verduri, Alessia; Bottazzi, Barbara; Stendardo, Mariarita; Fucili, Alessandro; Balduzzi, Sara; Leuzzi, Chiara; Papi, Alberto; Mantovani, Alberto; Fabbri, Leonardo; Ceconi, Claudio; Boschetto, Piera
abstract

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1 beta (IL-1 beta), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged >= 50 years and with >= 10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 beta, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 beta, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

2013 - Exacerbation of respiratory Symptoms in COPD patients may not be exacerbations of COPD [Articolo su rivista]
Beghe', Bianca; Verduri, Alessia; Roca, M; Fabbri, Leonardo
abstract

Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as acute events characterised by a worsening of the patient's respiratory symptoms, particularly dyspnoea, beyond day-to-day variation, leading to a change in medical treatment and/or hospitalisation. Exacerbations of COPD are a leading cause of hospitalisation and healthcare expenditures, particularly in frail, elderly patients. They alter the health-related quality of life and the natural course of disease, increasing the risk of mortality, both during and after the acute event. Patients with COPD frequently have chronic comorbidities. Several of these comorbidities may produce acute events, contributing to the increased morbidity and mortality in COPD exacerbations: acute myocardial infarction, congestive heart failure, cerebrovascular disease, cardiac arrhythmias and pulmonary circulation disorders.

2013 - Mechanisms of acute exacerbation of respiratory symptoms in chronic obstructive pulmonary disease [Articolo su rivista]
Roca, Mihai; Verduri, Alessia; Corbetta, Lorenzo; Clini, Enrico; Fabbri, Leonardo; Beghe', Bianca
abstract

Exacerbations of chronic obstructive respiratory disease (ECOPD) are acute events characterized by worsening of the patient's respiratory symptoms, particularly dyspnoea, leading to change in medical treatment and/or hospitalisation. AECOP are considered respiratory diseases, with reference to the respiratory nature of symptoms and to the involvement of airways and lung. Indeed respiratory infections and/or air pollution are the main causes of ECOPD. They cause an acute inflammation of the airways and the lung on top of the chronic inflammation that is associated with COPD. This acute inflammation is responsible of the development of acute respiratory symptoms (in these cases the term ECOPD is appropriate). However, the acute inflammation caused by infections/pollutants is almost associated with systemic inflammation, that may cause acute respiratory symptoms through decompensation of concomitant chronic diseases (eg acute heart failure, thromboembolism, etc) almost invariably associated with COPD. Most concomitant chronic diseases share with COPD not only the underlying chronic inflammation of the target organs (i.e. lungs, myocardium, vessels, adipose tissue), but also clinical manifestations like fatigue and dyspnoea. For this reason, in patients with multi-morbidity (eg COPD with chronic heart failure and hypertension, etc), the exacerbation of respiratory symptoms may be particularly difficult to investigate, as it may be caused by exacerbation of COPD and/or ≥ comorbidity, (e.g. decompensated heart failure, arrhythmias, thromboembolisms) without necessarily involving the airways and lung. In these cases the term ECOPD is inappropriate and misleading.

2011 - Roflumilast:un nuovo farmaco per il trattamento della BPCO [Articolo su rivista]
Beghe', Bianca; Verduri, Alessia; Fabbri, Leonardo
abstract

La broncopneumopatia cronica ostruttiva (BPCO) è una malattia respiratoria cronica il cui principale fattore di rischio è il fumo di sigaretta. La patologia è caratterizzata da una progressiva limitazione del flusso aereo non completamente reversibile, da sintomi respiratori quali tosse e dispnea e da frequenti riacutizzazioni cliniche che possono richiedere il ricovero ospedaliero con ulteriore compromissione dello stato di salute, declino della funzionalità respiratoria e aumento del tasso di mortalità. I farmaci attualmente disponibili per il trattamento della BPCO sono i broncodilatatori inalatori a breve (SABA) e a lunga durata d’azione (LABA). Nei pazienti con BPCO grave e molto grave e con frequenti riacutizzazioni i LABA sono somministrati in associazione con gli steroidi inalatori. L’infiammazione cronica dei polmoni gioca un ruolo cruciale nella patogenesi della BPCO. Gli inibitori della fosfodiesterasi 4 (PDE4) sono una nuova classe di farmaci ad azione antinfiammatoria che sono stati sviluppati per controllare l’infiammazione cronica correlata alla BPCO.Gli inibitori della fosfodiesterasi 4 hanno mostrato una buona efficacia e tollerabilità in studi preclinici e clinici condotti nei pazienti con BPCO

2011 - Subclinical cardiac dysfunction in moderate to severe COPD patients [Poster]
Verduri, Alessia; Bottazzi, B; Leuzzi, C; Boschetto, P; Modena, Mg; Mantovani, A; Fabbri, Leonardo; Beghe', Bianca
abstract

Non previsto