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1.
J Pain Symptom Manage ; 63(4): 468-475, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995682

RESUMO

BACKGROUND: The number of cancer patients potentially amenable to palliative care is conventionally estimated from cancer deaths, as reported in the death certificates. However, a more representative population should also include cancer patients who die from causes other than cancer, as they may develop other life-limiting chronic conditions leading to terminal prognosis. AIM: This study aimed at refining the assessment of the number of cancer patients potentially in need of palliative care, by linked hospital and death data. DESIGN: Retrospective study. SETTING/PARTICIPANTS: Residents in the Emilia Romagna Region in Italy, who died between 2009 and 2017. RESULTS: We identified a potential palliative care population of 157,547 cancer patients. The use of different administrative data sources enhanced the sensitivity of our selection. Starting from a standard estimate of 129,212 patients based on cancer as the primary cause of death, we showed that the additional use of hospital records identified a further 11.4% of possible palliative care patients 14,687. Also considering cancer as secondary cause of death, the estimate further increased by 10.6% (13,648 new cases). Notably, the proportion of cancer patients selected by the additional data sources were characterized by more advanced age and higher prevalence of comorbidity. CONCLUSION: Healthcare services addressing the issue of estimating palliative care needs of cancer patients at a population level should consider that relying on the death certificate alone may lead to underestimating these needs of about 22%.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Assistência Terminal , Humanos , Neoplasias/epidemiologia , Neoplasias/terapia , Cuidados Paliativos , Estudos Retrospectivos
2.
PLoS One ; 17(1): e0262908, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35081151

RESUMO

OBJECTIVE: The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. METHOD: This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. RESULTS: A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. CONCLUSIONS: Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Idoso , Proteína C-Reativa/análise , COVID-19/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Taxa Respiratória , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento
3.
Eur Respir J ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361632

RESUMO

RATIONALE: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. METHODS: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. RESULTS: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. CONCLUSIONS: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. MESSAGE OF THE STUDY: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia.

4.
Front Oncol ; 12: 855723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371993

RESUMO

Background: Frail patients are considered at relevant risk of complications due to coronavirus disease 2019 (COVID-19) infection and, for this reason, are prioritized candidates for vaccination. As these patients were originally not included in the registration trials, fear related to vaccine adverse events and disease worsening was one of the reasons for vaccine hesitancy. Herein, we report the safety profile of the prospective, multicenter, national VAX4FRAIL study (NCT04848493) to evaluate vaccines in a large trans-disease cohort of patients with solid or hematological malignancies and neurological and rheumatological diseases. Methods: Between March 3 and September 2, 2021, 566 patients were evaluable for safety endpoint: 105 received the mRNA-1273 vaccine and 461 the BNT162b2 vaccine. Frail patients were defined per protocol as patients under treatment with hematological malignancies (n = 131), solid tumors (n = 191), immune-rheumatological diseases (n = 86), and neurological diseases (n = 158), including multiple sclerosis and generalized myasthenia. The impact of the vaccination on the health status of patients was assessed through a questionnaire focused on the first week after each vaccine dose. Results: The most frequently reported moderate-severe adverse events were pain at the injection site (60.3% after the first dose, 55.4% after the second), fatigue (30.1%-41.7%), bone pain (27.4%-27.2%), and headache (11.8%-18.9%). Risk factors associated with the occurrence of severe symptoms after vaccine administration were identified through a multivariate logistic regression analysis: age was associated with severe fever presentation (younger patients vs. middle-aged vs. older ones), female individuals presented a higher probability of severe pain at the injection site, fatigue, headache, and bone pain; and the mRNA-1237 vaccine was associated with a higher probability of severe pain at the injection site and fever. After the first dose, patients presenting a severe symptom were at a relevant risk of recurrence of the same severe symptom after the second one. Overall, 11 patients (1.9%) after the first dose and 7 (1.2%) after the second one required postponement or suspension of the disease-specific treatment. Finally, two fatal events occurred among our 566 patients. These two events were considered unrelated to the vaccine. Conclusions: Our study reports that mRNA-COVID-19 vaccination is safe also in frail patients; as expected, side effects were manageable and had a minimum impact on patient care path.

5.
BMC Palliat Care ; 20(1): 193, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963453

RESUMO

BACKGROUND: Worldwide, millions of people with advanced cancer and their family caregivers are experiencing physical and psychological distress. Psychosocial support and education can reduce distress and prevent avoidable healthcare resource use. To date, we lack knowledge from large-scale studies on which interventions generate positive outcomes for people with cancer and their informal caregivers' quality of life. This protocol describes the DIAdIC study that will evaluate the effectiveness of two psychosocial and educational interventions aimed at improving patient-family caregiver dyads' emotional functioning and self-efficacy. METHODS: We will conduct an international multicenter three-arm randomized controlled trial in Belgium, Denmark, Ireland, Italy, The Netherlands, and the United Kingdom. In each country, 156 dyads (936 in total) of people with advanced cancer and their family caregiver will be randomized to one of the study arms: 1) a nurse-led face-to-face intervention (FOCUS+), 2) a web-based intervention (iFOCUS) or 3) a control group (care as usual). The two interventions offer tailored psychoeducational support for patient-family caregiver dyads. The nurse-led face-to-face intervention consists of two home visits and one online video session and the web-based intervention is completed independently by the patient-family caregiver dyad in four online sessions. The interventions are based on the FOCUS intervention, developed in the USA, that addresses five core components: family involvement, optimistic outlook, coping effectiveness, uncertainty reduction, and symptom management. The FOCUS intervention will be adapted to the European context. The primary outcomes are emotional functioning and self-efficacy of the patient and the family caregiver, respectively. The secondary outcomes are quality of life, benefits of illness, coping, dyadic communication, and ways of giving support of the patient and family caregiver. DISCUSSION: DIAdIC aims to develop cost-effective interventions that integrate principles of early palliative care into standard care. The cross-country setup in six European countries allows for comparison of effectiveness of the interventions in different healthcare systems across Europe. By focusing on empowerment of the person with cancer and their family caregiver, the results of this RCT can contribute to the search for cost-effective novel interventions that can relieve constraints on professional healthcare. TRIAL REGISTRATION: Registration on ClinicalTrials.gov on 12/11/2020, identifier NCT04626349 . DATE AND VERSION IDENTIFIER: 20211209_DIAdIC_Protocol_Article.


Assuntos
Cuidadores , Neoplasias , Humanos , Internet , Estudos Multicêntricos como Assunto , Neoplasias/terapia , Sistemas de Apoio Psicossocial , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Front Immunol ; 12: 704110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447374

RESUMO

Patients diagnosed with malignancy, neurological and immunological disorders, i.e., fragile patients, have been excluded from COVID-19 vaccine trials. However, this population may present immune response abnormalities, and relative reduced vaccine responsiveness. Here we review the limited current evidence on the immune responses to vaccination of patients with different underlying diseases. To address open questions we present the VAX4FRAIL study aimed at assessing immune responses to vaccination in a large transdisease cohort of patients with cancer, neurological and rheumatological diseases.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Adulto , Vacinas contra COVID-19/imunologia , Protocolos Clínicos , Humanos , Doenças do Sistema Imunitário/imunologia , Hospedeiro Imunocomprometido/imunologia , Neoplasias/imunologia , Doenças do Sistema Nervoso/imunologia , Seleção de Pacientes , Estudos Prospectivos
8.
Indian J Palliat Care ; 27(1): 152-171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34035634

RESUMO

BACKGROUND: COVID-19 has been causing a high burden of suffering for patients and families. There is limited evidence on the preparedness of Indian palliative care services for the pandemic. AIM: This study aimed to assess the preparedness and capacity of Indian palliative care services in response to the COVID-19 pandemic. METHODS: A cross-sectional online survey was developed based on prior evidence and international health regulations. It was emailed to the Indian Palliative Care Association members and investigators' professional networks in India. One participant per palliative care service was requested. Descriptive analysis was used. RESULTS: Representatives of 78 palliative care services completed the survey. Three in four services had COVID-19 case definition and adapted their protocols for infection control (75%). About half of the services (55%) reported concerns about achieving appropriate hand hygiene in the community. More than half of the services (59%) had capacity to train nonspecialists for symptom control and psychological support. About half of the services reported that they had plans to redeploy staff (56%) and resources (53%) in the case of outbreaks. Two-fifths of the services used paper records to store an updated contact list of staff (40%) and did not have designated focal contacts for information update (40%). Staff anxiety related to personal infection risk and family care was relatively high (median score = 7 on a 1-10 scale). CONCLUSION: We recommend the following resource allocation to enable palliative care services to support the Indian health system in delivering essential care in this and future pandemics: (1) infection control, especially in the community; (2) training using existing clinical protocols to strengthen palliative care across the health system; and (3) redeployment plans.

9.
BMC Health Serv Res ; 21(1): 446, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975580

RESUMO

BACKGROUND: A quality accreditation program (AP) is designed to guarantee predefined quality standards of healthcare organizations. Evidence of the impact of quality standards remains scarce and somewhat challenging to document. This study aimed to investigate the accreditation of a cancer research hospital (Italy), promoted by the Organization of European Cancer Institutes (OECI), by focusing on the individual, group, and organizational experiences resulting from the OECI AP. METHODS: A focused ethnography study was carried out to analyze the relevance of participation in the accreditation process. Twenty-nine key informants were involved in four focus group meetings, and twelve semistructured interviews were conducted with professionals and managers. Inductive qualitative content analysis was applied to examine all transcripts. RESULTS: Four main categories emerged: a) OECI AP as an opportunity to foster diversity within professional roles; b) OECI AP as a possibility for change; c) perceived barriers; and d) OECI AP-solicited expectations. CONCLUSIONS: The accreditation process is an opportunity for improving the quality and variety of care services for cancer patients through promoting an interdisciplinary approach to care provision. Perceiving accreditation as an opportunity is a prerequisite for overcoming the barriers that professionals involved in the process may report. Critical to a positive change is sharing the values and the framework, which are at the basis of accreditation programs. Improving the information-sharing process among managers and professionals may limit the risk of unmet expectations and prevent demotivation by future accreditation programs. Finally, we found that positive changes are more likely to happen when an accreditation process is considered an activity whose results depend on managers' and professionals' joint work.


Assuntos
Acreditação , Neoplasias , Antropologia Cultural , Institutos de Câncer , Humanos , Itália , Neoplasias/terapia
10.
J Clin Pathol ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893155

RESUMO

AIMS: The progressive increase of both the workload and the complexity of laboratory procedures, along with shortage of staff, has made evident the need to increase the efficiency in the pathology departments. To support the pathologists, a new technical professional role, the pathologists' assistant (PA), has been introduced. METHODS: We decided to carry out a retrospective analysis on PAs' performance. This was compared with that of junior/senior pathologists in the amount and type of surgical specimens examined, the number of lymph node retrieved in colorectal resections, the number of cases needing a second grossing procedure and the average time spent in grossing. As the COVID-19 pandemic period in fact resulted in a dramatic reduction of histological cases in our department, we divided PA activities into two periods, according to the COVID-19 pandemic. RESULTS: 'Simple' specimens made up the majority (92%) of the specimens examined by PAs in pre-COVID-19 period while 'complex' specimens, often neoplastic, represented the minor part (7%). However, 'simple' specimens dropped to 81% and 'complex' specimens rose to 18% in the COVID-19 period, when PAs had the chance to test themselves with more complicated surgical samples, under the supervision of a pathologist. Lymph node retrieval rate and average time spent in grossing are in line with literature data and confirm that PAs performance is comparable with pathologists' one, in selected settings. CONCLUSION: In our experience, PA has represented a fundamental time-saving resource for the pathologists, who can devote time almost exclusively to diagnostic reporting.

11.
Clin Exp Rheumatol ; 39(5): 1119-1125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33635218

RESUMO

OBJECTIVES: The results of the RECOVERY trial identified dexamethasone as the first pharmacological therapy that reduces mortality in patients with COVID-19. The aim of this paper is to conduct a systematic literature review on safety and efficacy of pulse glucocorticoid therapy for Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV), Middle East Respiratory Syndrome (MERS)-CoV or SARS-CoV-2 infections and describe a case-series of COVID-19 patients treated with off-label pulse doses of methylprednisolone. METHODS: We performed a systematic literature review on safety and efficacy of pulse therapy for betacoronaviridae infections as described in the protocol registered on PROSPERO (CRD42020190183). All consecutive patients admitted to Arcispedale Santa Maria Nuova di Reggio Emilia or Guastalla Hospital with COVID-19 between March 1st and April 30th, 2020 and treated with methylprednisolone 1 gram/day for at least three days were included in the case series. A retrospective review of available computed tomography (CT) scan and chest x-ray was performed independently by two radiologists blinded to clinical data, and discordances were resolved by consensus. RESULTS: Twenty papers were included for SARS, but only two were comparative and were included in the primary endpoint analysis. Likewise, eleven papers were included for COVID-19, four of which were comparative and were considered for the primary outcome analysis. Included studies for both SARS and COVID-19 are mostly retrospective and highly heterogeneous, with lethality ranging from 0% to 100% and ICU admission rate ranging from 9% to 100%. Fourteen patients were included in our case series, 7 males and 7 females. CONCLUSIONS: No randomised controlled trial is available yet for corticosteroids pulse-therapy defined as at least ≥500mg/day methylprednisolone in patients with emerging coronavirus pneumonia. Lethality among our cohort is high (4/14), but this finding should be interpreted with caution due to the fact that in our setting pulse-steroids were used in patients not eligible for other treatments because of comorbidities or as rescue therapy. The incidence of steroid-related adverse events seems low in our cohort. The quality of the evidence on glucocorticoid pulse-therapy in SARS, MERS and COVID-19 is poor. Randomised controlled trials are greatly needed.


Assuntos
COVID-19 , Coronaviridae , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento
12.
Eur J Neurol ; 28(10): 3254-3262, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33460507

RESUMO

BACKGROUND AND PURPOSE: During the first phase of the COVID-19 pandemic, a lockdown was imposed in Italy. The aim of this study was to investigate the perceptions, feelings and unmet needs of Parkinson's disease (PD) patients who experienced the 2-month lockdown in a "red zone" in the northern part of Italy during the COVID-19 outbreak. METHODS: The study had a descriptive design that used a cross-sectional online survey which included open-ended questions to elicit responses on the participant's feelings concerning their risk of contracting coronavirus, how their physical activity had changed, and their personal needs, dictated by their condition, which were not met in this pandemic period as compared to previous periods. Demographic data were analysed using descriptive frequencies, while the open-ended questions were analysed using thematic framework analysis. RESULTS: The study included 103 participants (63 men/40 women [61.17 vs. 38.83%]). Framework analysis led to the identification of four main themes: (i) fearing the risk of contracting coronavirus; (ii) reduction of physical activity; (iii) perception of the risk of not being able to access outpatient clinics or support services; and (iv) negative experiences of the important reduction in socialization. The perceptions of unmet needs appeared to be greater than the actual experience, particularly for the reduction in physical activity and the interruption of contacts with the neurologist and other specialists. CONCLUSIONS: This study highlights how perceptions and actual experience shape the meaning of living with PD during the pandemic. Worth noting is the divergence between perceptions and real impact in some aspects of the COVID-19 outbreak.


Assuntos
COVID-19 , Doença de Parkinson , Controle de Doenças Transmissíveis , Estudos Transversais , Feminino , Humanos , Masculino , Pandemias , Doença de Parkinson/epidemiologia , SARS-CoV-2 , Inquéritos e Questionários
13.
Arthritis Rheumatol ; 73(1): 48-52, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32767527

RESUMO

OBJECTIVE: To evaluate the susceptibility to coronavirus disease 2019 (COVID-19) in patients with autoimmune conditions treated with antimalarials in a population-based study. METHODS: All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia-Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94-1.28]), the same probability of being diagnosed as having COVID-19 (OR 0.94 [95% CI 0.66-1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56-1.23]). None of the differences were significant. CONCLUSION: Our findings do not support the use of antimalarials as a prophylactic treatment of COVID-19.


Assuntos
Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , COVID-19/epidemiologia , Cloroquina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimaláricos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , COVID-19/prevenção & controle , Suscetibilidade a Doenças , Feminino , Humanos , Itália/epidemiologia , Lúpus Eritematoso Discoide/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Razão de Chances , SARS-CoV-2
14.
JAMA Intern Med ; 181(1): 24-31, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080005

RESUMO

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. Design, Setting, and Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. Main Outcome and Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first. Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. Conclusions and Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/terapia , Idoso , Gasometria , Proteína C-Reativa/metabolismo , COVID-19/metabolismo , COVID-19/fisiopatologia , Progressão da Doença , Término Precoce de Ensaios Clínicos , Feminino , Febre , Hospitalização , Humanos , Itália , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Receptores de Interleucina-6/antagonistas & inibidores , Insuficiência Respiratória/fisiopatologia , SARS-CoV-2
15.
Clin Exp Rheumatol ; 38(6): 1215-1222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33275095

RESUMO

OBJECTIVES: To identify predictors of clinical improvement and intubation/death in tocilizumab-treated severe COVID19, focusing on IL6 and CRP longitudinal monitoring. METHODS: 173 consecutive patients with severe COVID-19 pneumonia receiving tocilizumab in Reggio Emilia province Hospitals between 11 March and 3 June 2020 were enrolled in a prospective cohort study. Clinical improvement was defined as status improvement on a six-category ordinal scale or discharge from the hospital, whichever came first. A composite outcome of intubation/death was also evaluated. CRP and IL-6 levels were determined before TCZ administration (T0) and after 3 (T3), and 7 (T7) days. RESULTS: At multivariate analysis T0 and T3 CRP levels were negatively associated with clinical improvement (OR 0.13, CI 0.03-0.55 and OR 0.11, CI 0.0-0.46) (p=0.006 and p=0.003) and positively associated with intubation/death (OR 17.66, CI 2.47-126.14 and OR 5.34, CI: 1.49-19.12) (p=0.01 and p=0.004). No significant associations with IL-6 values were observed. General linear model analyses for repeated measures showed significantly different trends for CRP from day 3 to day 7 between patients who improved and those who did not, and between patients who were intubated or died and those who were not (p<0.0001 for both). ROC analysis identified a baseline CRP level of 15.8 mg/dl as the best cut-off to predict intubation/death (AUC = 0.711, sensitivity = 0.67, specificity = 0.71). CONCLUSIONS: CRP serial measurements in the first week of TCZ therapy are useful in identifying patients developing poor outcomes.


Assuntos
Betacoronavirus , COVID-19 , Infecções por Coronavirus , Pneumonia Viral , Proteínas de Fase Aguda , Anticorpos Monoclonais Humanizados , Humanos , Pandemias , Estudos Prospectivos , SARS-CoV-2
16.
J Transl Med ; 18(1): 405, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087150

RESUMO

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/imunologia , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Uso Off-Label , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Resultado do Tratamento , Estudos de Validação como Assunto
17.
BMJ Support Palliat Care ; 10(4): 395-403, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33055091

RESUMO

BACKGROUND: Early palliative care together with standard haematological care for advanced patients is needed worldwide. Little is known about its effect. The aim of the review is to synthesise the evidence on the impact of early palliative care on haematologic cancer patients' quality of life and resource use. PATIENTS AND METHODS: A systematic review was conducted. The search terms were early palliative care or simultaneous or integrated or concurrent care and haematological or oncohaematological patients. The following databases were searched: PubMed, Embase, Cochrane, CINHAL and Scopus. Additional studies were identified through cross-checking the reference articles. Studies were in the English language, with no restriction for years. Two researchers independently reviewed the titles and abstracts, and one author assessed full articles for eligibility. RESULTS: A total of 296 studies titles were reviewed. Eight articles were included in the synthesis of the results, two controlled studies provided data on the comparative efficacy of PC interventions, and six one-arm studies were included. Since data pooling and meta-analysis were not possible, only a narrative synthesis of the study results was performed. The quality of the two included comparative studies was low overall. The quality of the six non-comparative studies was high overall, without the possibility of linking the observed results to the implemented interventions. CONCLUSIONS: Studies on early palliative care and patients with haematological cancer are scarce and have not been prospectively designed. More research on the specific population target, type and timing of palliative care intervention and standardisation of collected outcomes is required. PROSPERO REGISTRATION NUMBER: CRD42020141322.


Assuntos
Neoplasias Hematológicas/terapia , Cuidados Paliativos , Intervenção Médica Precoce , Humanos , Qualidade de Vida
18.
Contemp Clin Trials ; 98: 106165, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33031955

RESUMO

BACKGROUND: Pneumonia is the most frequent complication of COVID-19, due to an aberrant host immune response that is associated with an acute respiratory distress syndrome, and, in most critical patients, with a "cytokine storm". IL-6 might play a key role in the cytokine storm and might be a potential target to treat severe and critical COVID-19. Tocilizumab is a recombinant humanized monoclonal antibody, directed against IL-6 receptor. METHODS: This multicentre study project includes a single-arm phase 2 study and a further parallel cohort, enrolling hospitalized patients with COVID-19 pneumonia and oxygen saturation at rest in ambient air ≤93% or requiring respiratory support. Patients receive tocilizumab 8 mg/kg (up to 800 mg) as one intravenous administration. A second administration (same dose) after 12 h is optional. Two-week and one-month lethality rates are the co-primary endpoints. Sample size planned for the phase 2 study is 330 patients. The parallel cohort will include patients who cannot enter the phase 2 study because being intubated from more than 24 h, or having already received tocilizumab, or the phase 2 study has reached sample size. Primary analysis will include patients enrolled in the phase 2 study. Results of the primary analysis will be validated in the prospective cohort of patients consecutively registered after phase 2 closure from March 20 to March 24, who were potentially eligible for the phase 2 study. CONCLUSION: This trial aims to verify the safety and efficacy of tocilizumab in the Italian population with COVID-19 pneumonia and respiratory impairment. EudraCT Number: 2020-001110-38; Clinicaltrials.gov ID NCT04317092.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Síndrome da Liberação de Citocina , Pneumonia Viral , Receptores de Interleucina-6/antagonistas & inibidores , Administração Intravenosa , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/complicações , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/terapia , Ensaios Clínicos Fase II como Assunto , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Masculino , Estudos Multicêntricos como Assunto , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Resultado do Tratamento
19.
Cochrane Database Syst Rev ; 9: CD012780, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32996586

RESUMO

BACKGROUND: Serious illness is often characterised by physical/psychological problems, family support needs, and high healthcare resource use. Hospital-based specialist palliative care (HSPC) has developed to assist in better meeting the needs of patients and their families and potentially reducing hospital care expenditure. There is a need for clarity on the effectiveness and optimal models of HSPC, given that most people still die in hospital and also to allocate scarce resources judiciously. OBJECTIVES: To assess the effectiveness and cost-effectiveness of HSPC compared to usual care for adults with advanced illness (hereafter patients) and their unpaid caregivers/families. SEARCH METHODS: We searched CENTRAL, CDSR, DARE and HTA database via the Cochrane Library; MEDLINE; Embase; CINAHL; PsycINFO; CareSearch; National Health Service Economic Evaluation Database (NHS EED) and two trial registers to August 2019, together with checking of reference lists and relevant systematic reviews, citation searching and contact with experts to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the impact of HSPC on outcomes for patients or their unpaid caregivers/families, or both. HSPC was defined as specialist palliative care delivered by a palliative care team that is based in a hospital providing holistic care, co-ordination by a multidisciplinary team, and collaboration between HSPC providers and generalists. HSPC was provided to patients while they were admitted as inpatients to acute care hospitals, outpatients or patients receiving care from hospital outreach teams at home. The comparator was usual care, defined as inpatient or outpatient hospital care without specialist palliative care input at the point of entry into the study, community care or hospice care provided outside of the hospital setting. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed risk of bias and extracted data. To account for use of different scales across studies, we calculated standardised mean differences (SMDs) with 95% confidence intervals (CIs) for continuous data. We used an inverse variance random-effects model. For binary data, we calculated odds ratio (ORs) with 95% CIs. We assessed the evidence using GRADE and created a 'Summary of findings' table. Our primary outcomes were patient health-related quality of life (HRQoL) and symptom burden (a collection of two or more symptoms). Key secondary outcomes were pain, depression, satisfaction with care, achieving preferred place of death, mortality/survival, unpaid caregiver burden, and cost-effectiveness. Qualitative data was analysed where available. MAIN RESULTS: We identified 42 RCTs involving 7779 participants (6678 patients and 1101 caregivers/family members). Twenty-one studies were with cancer populations, 14 were with non-cancer populations (of which six were with heart failure patients), and seven with mixed cancer and non-cancer populations (mixed diagnoses). HSPC was offered in different ways and included the following models: ward-based, inpatient consult, outpatient, hospital-at-home or hospital outreach, and service provision across multiple settings which included hospital. For our main analyses, we pooled data from studies reporting adjusted endpoint values. Forty studies had a high risk of bias in at least one domain. Compared with usual care, HSPC improved patient HRQoL with a small effect size of 0.26 SMD over usual care (95% CI 0.15 to 0.37; I2 = 3%, 10 studies, 1344 participants, low-quality evidence, higher scores indicate better patient HRQoL). HSPC also improved other person-centred outcomes. It reduced patient symptom burden with a small effect size of -0.26 SMD over usual care (95% CI -0.41 to -0.12; I2 = 0%, 6 studies, 761 participants, very low-quality evidence, lower scores indicate lower symptom burden). HSPC improved patient satisfaction with care with a small effect size of 0.36 SMD over usual care (95% CI 0.41 to 0.57; I2 = 0%, 2 studies, 337 participants, low-quality evidence, higher scores indicate better patient satisfaction with care). Using home death as a proxy measure for achieving patient's preferred place of death, patients were more likely to die at home with HSPC compared to usual care (OR 1.63, 95% CI 1.23 to 2.16; I2 = 0%, 7 studies, 861 participants, low-quality evidence). Data on pain (4 studies, 525 participants) showed no evidence of a difference between HSPC and usual care (SMD -0.16, 95% CI -0.33 to 0.01; I2 = 0%, very low-quality evidence). Eight studies (N = 1252 participants) reported on adverse events and very low-quality evidence did not demonstrate an effect of HSPC on serious harms. Two studies (170 participants) presented data on caregiver burden and both found no evidence of effect of HSPC (very low-quality evidence). We included 13 economic studies (2103 participants). Overall, the evidence on cost-effectiveness of HSPC compared to usual care was inconsistent among the four full economic studies. Other studies that used only partial economic analysis and those that presented more limited resource use and cost information also had inconsistent results (very low-quality evidence). Quality of the evidence The quality of the evidence assessed using GRADE was very low to low, downgraded due to a high risk of bias, inconsistency and imprecision. AUTHORS' CONCLUSIONS: Very low- to low-quality evidence suggests that when compared to usual care, HSPC may offer small benefits for several person-centred outcomes including patient HRQoL, symptom burden and patient satisfaction with care, while also increasing the chances of patients dying in their preferred place (measured by home death). While we found no evidence that HSPC causes serious harms, the evidence was insufficient to draw strong conclusions. Although these are only small effect sizes, they may be clinically relevant at an advanced stage of disease with limited prognosis, and are person-centred outcomes important to many patients and families. More well conducted studies are needed to study populations with non-malignant diseases and mixed diagnoses, ward-based models of HSPC, 24 hours access (out-of-hours care) as part of HSPC, pain, achieving patient preferred place of care, patient satisfaction with care, caregiver outcomes (satisfaction with care, burden, depression, anxiety, grief, quality of life), and cost-effectiveness of HSPC. In addition, research is needed to provide validated person-centred outcomes to be used across studies and populations.


Assuntos
Cuidadores/estatística & dados numéricos , Serviços Hospitalares de Assistência Domiciliar/economia , Cuidados Paliativos/economia , Cuidados Paliativos/métodos , Assistência Terminal/economia , Assistência Terminal/métodos , Assistência Ambulatorial/economia , Viés , Cuidadores/psicologia , Análise Custo-Benefício , Família , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização/economia , Humanos , Neoplasias/mortalidade , Neoplasias/terapia , Manejo da Dor/estatística & dados numéricos , Satisfação do Paciente , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Avaliação de Sintomas/estatística & dados numéricos
20.
Cancers (Basel) ; 12(9)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917028

RESUMO

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced "dysplastic-like" features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions.

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