Showing papers by "Giovanni F.M. Strippoli published in 2020"
01 Jan 2020
TL;DR: In this paper, the authors evaluated the number, quality, and coverage of randomized controlled trials (RCT) in nephrology and found that the quality of RCT reporting has not improved over the past 30 years with unclear allocation concealment (89%), lack of reported blinding of outcome assessors (92%), and failure to perform?intention-to-treat analysis? particularly frequent.
Abstract: Randomized controlled trials (RCT) are the optimal study design to answer intervention questions. The authors evaluated the number, quality, and coverage of RCT in nephrology. MEDLINE was searched using the relevant medical subject headings for nephrology and 12 major specialties in internal medicine, limited by ?randomized controlled trial? as a publication type. A random selection of 160 RCT in nephrology (40 for each decade) published since 1966 and an additional 270 RCT from ongoing or published Cochrane systematic reviews in various areas of nephrology, dialysis, and transplantation were evaluated for quality of reporting using standard criteria. The number of RCT published in nephrology from 1966 to 2002 (2779) is fewer than all other specialties of internal medicine (range: 5335 in hematology to 27109 in cardiology) with the proportion of all citations which are RCT being the third lowest (1.15%). There has been an increase in both indices from 1966 to 1996, but not at a greater rate than other specialties, and there has been no increase over the past 5 yr. Some areas of nephrology, in particular glomerulonephritis, are clear outliers with very low numbers of RCT to guide clinical decision-making. Overall the quality of RCT reporting in nephrology is low and has not improved over the past 30 yr with unclear allocation concealment (89%), lack of reported blinding of outcome assessors (92%), and failure to perform ?intention-to-treat analysis? (50%) particularly frequent. The challenges of improving the quality and quantity of trials in nephrology are substantial, but they can be overcome by using standard guidelines and checklists for trial reporting, greater attention to the trial methods and not just the results, involving experts in trial design and reporting, multicenter collaboration, and larger and simpler trials.
268 citations
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TL;DR: The effects of aldosterone antagonists in adults who have CKD with proteinuria, non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone) in adults with CKD are evaluated.
Abstract: Background Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a Cochrane review first published in 2009 and updated in 2014. Objectives To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia). Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 13 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists in combination with ACEi or ARB (or both) to other anti-hypertensive strategies or placebo in participants with proteinuric CKD. Data collection and analysis Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used together with their 95% confidence interval (CI). Risk of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE. Main results Forty-four studies (5745 participants) were included. Risk of bias in the evaluated methodological domains were unclear or high risk in most studies. Adequate random sequence generation was present in 12 studies, allocation concealment in five studies, blinding of participant and investigators in 18 studies, blinding of outcome assessment in 15 studies, and complete outcome reporting in 24 studies. All studies comparing aldosterone antagonists to placebo or standard care were used in addition to an ACEi or ARB (or both). None of the studies were powered to detect differences in patient-level outcomes including kidney failure, major cardiovascular events or death. Aldosterone antagonists had uncertain effects on kidney failure (2 studies, 84 participants: RR 3.00, 95% CI 0.33 to 27.65, I² = 0%; very low certainty evidence), death (3 studies, 421 participants: RR 0.58, 95% CI 0.10 to 3.50, I² = 0%; low certainty evidence), and cardiovascular events (3 studies, 1067 participants: RR 0.95, 95% CI 0.26 to 3.56; I² = 42%; low certainty evidence) compared to placebo or standard care. Aldosterone antagonists may reduce protein excretion (14 studies, 1193 participants: SMD -0.51, 95% CI -0.82 to -0.20, I² = 82%; very low certainty evidence), eGFR (13 studies, 1165 participants, MD -3.00 mL/min/1.73 m², 95% CI -5.51 to -0.49, I² = 0%, low certainty evidence) and systolic blood pressure (14 studies, 911 participants: MD -4.98 mmHg, 95% CI -8.22 to -1.75, I² = 87%; very low certainty evidence) compared to placebo or standard care. Aldosterone antagonists probably increase the risk of hyperkalaemia (17 studies, 3001 participants: RR 2.17, 95% CI 1.47 to 3.22, I² = 0%; moderate certainty evidence), acute kidney injury (5 studies, 1446 participants: RR 2.04, 95% CI 1.05 to 3.97, I² = 0%; moderate certainty evidence), and gynaecomastia (4 studies, 281 participants: RR 5.14, 95% CI 1.14 to 23.23, I² = 0%; moderate certainty evidence) compared to placebo or standard care. Non-selective aldosterone antagonists plus ACEi or ARB had uncertain effects on protein excretion (2 studies, 139 participants: SMD -1.59, 95% CI -3.80 to 0.62, I² = 93%; very low certainty evidence) but may increase serum potassium (2 studies, 121 participants: MD 0.31 mEq/L, 95% CI 0.17 to 0.45, I² = 0%; low certainty evidence) compared to diuretics plus ACEi or ARB. Selective aldosterone antagonists may increase the risk of hyperkalaemia (2 studies, 500 participants: RR 1.62, 95% CI 0.66 to 3.95, I² = 0%; low certainty evidence) compared ACEi or ARB (or both). There were insufficient studies to perform meta-analyses for the comparison between non-selective aldosterone antagonists and calcium channel blockers, selective aldosterone antagonists plus ACEi or ARB (or both) and nitrate plus ACEi or ARB (or both), and non-steroidal mineralocorticoid antagonists and selective aldosterone antagonists. Authors' conclusions The effects of aldosterone antagonists when added to ACEi or ARB (or both) on the risks of death, major cardiovascular events, and kidney failure in people with proteinuric CKD are uncertain. Aldosterone antagonists may reduce proteinuria, eGFR, and systolic blood pressure in adults who have mild to moderate CKD but may increase the risk of hyperkalaemia, acute kidney injury and gynaecomastia when added to ACEi and/or ARB.
63 citations
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University of Sydney1, Monash University2, Flinders University3, Denver Health Medical Center4, University of Queensland5, University of Colorado Denver6, University of Oxford7, Kyungpook National University8, University of Chile9, University of Toronto10, Telethon Institute for Child Health Research11, Boston Children's Hospital12, University of the Witwatersrand13, University of Cambridge14, Lille University of Science and Technology15, University of Southern Denmark16, Nova Southeastern University17, University of Jena18, Peking University19, University of Nottingham20, University of Barcelona21, University of Liverpool22, Baylor College of Medicine23, Tianjin University of Traditional Chinese Medicine24
TL;DR: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials.
Abstract: Objectives: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient rele-vance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019.
Design: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus di-sease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set.
Setting: International.
Subjects: Adults 18 years old and over with confirmed or sus-pected coronavirus disease 2019, their family members, mem-bers of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers).
Interventions: None.
Measurements: None.
Main Results: Six themes were identified. “Responding to the crit-ical and acute health crisis” reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. “Capturing different settings of care” highlighted the need to minimize the burden on hospitals and to acknowledge out-comes in community settings. “Encompassing the full trajectory and severity of disease” was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). “Dis-tinguishing overlap, correlation and collinearity” meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). “Recognizing adverse events” refers to the potential harms of new and evolving interventions. “Being cognizant of family and psychosocial wellbeing” reflected the pervasive impacts of coronavirus disease 2019.
Conclusions: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important out-comes to be consistently reported in coronavirus disease 2019 trials.
43 citations
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TL;DR: A negative coronary CT angiography has a higher test performance than other index tests to exclude clinically-important CAD and a positive stress myocardial CT perfusion added to coronary CTAngiography, stress cardiac MR, and PET have aHigher test performance to identify patients requiring invasive coronary artery evaluation.
42 citations
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TL;DR: In this article, the effects of supplementing long chain omega-3 polyunsaturated fatty acids (n-3 PUFA) with dietary supplements for patients with chronic kidney disease (CKD) were evaluated.
42 citations
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TL;DR: The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness.
Abstract: Introduction End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD. Methods and analysis This international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years’ follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness. Ethics and dissemination The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness. Trial registration number Netherlands National Trial Register (NTR 7138).
36 citations
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University of Sydney1, Children's Hospital at Westmead2, University of Leicester3, University of New Mexico4, University of Alberta5, University of the Republic6, University of Pittsburgh7, Royal Derby Hospital8, University of Massachusetts Amherst9, University Health Network10, Panamerican University11, University of Salford12, University of Queensland13, Princess Alexandra Hospital14, University of Bari15, Royal North Shore Hospital16, Baylor College of Medicine17, Flinders University18
TL;DR: SONG-HD Fatigue seems to be a reliable and valid measure to be used in trials involving patients receiving hemodialysis, and demonstrated convergence with Functional Assessment of Chronic Illness Therapy-Fatigue and had moderate correlations with other measures that assessed related but not the same concept.
Abstract: Background and objectives Fatigue is a very common and debilitating symptom and identified by patients as a critically important core outcome to be included in all trials involving patients receiving hemodialysis. A valid, standardized measure for fatigue is needed to yield meaningful and relevant evidence about this outcome. This study validated a core patient-reported outcome measure for fatigue in hemodialysis. Design, setting, participants, & measurements A longitudinal cohort study was conducted to assess the validity and reliability of a new fatigue measure (Standardized Outcomes in Nephrology-Hemodialysis Fatigue [SONG-HD Fatigue]). Eligible and consenting patients completed the measure at three time points: baseline, a week later, and 12 days following the second time point. Cronbach α and intraclass correlation coefficient were calculated to assess internal consistency, and Spearman rho was used to assess convergent validity. Confirmatory factor analysis was also conducted. Hemodialysis units in the United Kingdom, Australia, and Romania participated in this study. Adult patients aged 18 years and over who were English speaking and receiving maintenance hemodialysis were eligible to participate. Standardized Outcomes in Nephrology-Hemodialysis, the Visual Analog Scale for fatigue, the 12-Item Short Form Survey, and Functional Assessment of Chronic Illness Therapy–Fatigue were used. Results In total, 485 participants completed the study across the United Kingdom, Australia, and Romania. Psychometric assessment demonstrated that Standardized Outcomes in Nephrology-Hemodialysis is internally consistent (Cronbach α =0.81–0.86) and stable over a 1-week period (intraclass correlation coefficient =0.68–0.74). The measure demonstrated convergence with Functional Assessment of Chronic Illness Therapy–Fatigue and had moderate correlations with other measures that assessed related but not the same concept (the 12-Item Short Form Survey and the Visual Analog Scale). Confirmatory factor analysis supported the one-factor model. Conclusions SONG-HD Fatigue seems to be a reliable and valid measure to be used in trials involving patients receiving hemodialysis.
29 citations
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TL;DR: Evidence of the benefits of calcimimetic therapy is limited to short-term assessment of a putative surrogate outcome (serum PTH).
25 citations
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TL;DR: Investigators should establish research consciousness from the time of diagnosis, consider optimal timing for approaching patients, provide comprehensive information in an accessible manner, emphasize current and future relevance to them and their illness, involve trusted clinicians in recruitment and minimize the burden of trial participation.
Abstract: BACKGROUND: Slow recruitment and poor retention jeopardize the reliability and statistical power of clinical trials, delaying access to effective interventions and increasing costs, as commonly observed in nephrology trials. Involving patients in trial design, recruitment and retention is infrequent but potentially transformational. METHODS: We conducted three workshops involving 105 patients/caregivers and 43 health professionals discussing patient recruitment and retention in clinical trials in chronic kidney disease. RESULTS: We identified four themes. 'Navigating the unknown'-patients described being unaware of the research question, confused by technical terms, sceptical about findings and feared the risk of harm. 'Wary of added burden'-patients voiced reluctance to attend additional appointments, were unsure of the commitment required or at times felt too unwell and without capacity to participate. 'Disillusioned and disconnected'-some patients felt they were taken for granted, particularly if they did not receive trial results. Participants believed there was no culture of trial participation in kidney disease and an overall lack of awareness about opportunities to participate. To improve recruitment and retention, participants addressed 'Building motivation and interest'. CONCLUSIONS: Investigators should establish research consciousness from the time of diagnosis, consider optimal timing for approaching patients, provide comprehensive information in an accessible manner, emphasize current and future relevance to them and their illness, involve trusted clinicians in recruitment and minimize the burden of trial participation. Participation in clinical trials was seen as an opportunity for people to give back to the health system and for future people in their predicament.
19 citations
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TL;DR: These findings did not confirm an association between mortality among patients receiving long-term hemodialysis and the extent to which dietary patterns were either high in fruit and vegetables or consistent with a Western diet.
13 citations
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University of Sydney1, Monash University2, Flinders University3, Anschutz Medical Campus4, Denver Health Medical Center5, University of Colorado Denver6, University of Oxford7, Kyungpook National University8, University of Chile9, University of Toronto10, Telethon Institute for Child Health Research11, University of the Witwatersrand12, University of Cambridge13, Lille University of Science and Technology14, Nova Southeastern University15, University of Jena16, Peking University17, University of Bari18, University of Nottingham19, University of Liverpool20, Baylor College of Medicine21, Tianjin University of Traditional Chinese Medicine22, University of Queensland23, Boston Children's Hospital24
TL;DR: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups and gave higher priority to many patient-reported outcomes compared with health professionals.
Abstract: Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. Design: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. Setting: International. Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). Interventions: None. Measurements: None. Main Results: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.
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Children's Hospital at Westmead1, University of Sydney2, Princess Alexandra Hospital3, University of Queensland4, Flinders University5, François Rabelais University6, French Institute of Health and Medical Research7, Clinical Trial Service Unit8, Hennepin County Medical Center9, Aga Khan University10, National University of Singapore11, Concord Repatriation General Hospital12, The George Institute for Global Health13, University of Würzburg14, University of British Columbia15, Medical University of Warsaw16, Wake Forest University17, University of Calgary18, University of Hong Kong19, University of Lorraine20, Baylor College of Medicine21, University College London22
TL;DR: A consensus workshop was held to discuss the potential use of myocardial infarction and sudden cardiac death as core outcome measures for CVD for use in all trials in people receiving hemodialysis.
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14 Nov 2020
TL;DR: This work aims to demonstrate the importance of knowing the carrier and removal status of canine coronavirus to the diagnosis and treatment of Alzheimer's disease.
Abstract: ACM is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z)