Showing papers by "Giovanni F.M. Strippoli published in 2021"

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Abstract: Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180.

Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery.

Abstract: OBJECTIVES: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019. DESIGN: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery. SETTING: International. PATIENTS: About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respiratory failure, assessed by the need for respiratory support based on the World Health Organization Clinical Progression Scale, was considered pragmatic, objective, and with broad applicability to various clinical scenarios. The Sequential Organ Failure Assessment was recommended for multiple organ failure, because it was routinely used in trials and clinical care, well validated, and feasible. The Modified Medical Research Council measure for shortness of breath, with minor adaptations (recall period of 24 hr to capture daily fluctuations and inclusion of activities to ensure relevance and to capture the extreme severity of shortness of breath in people with coronavirus disease 2019), was regarded as fit for purpose for this indication. The recovery measure was developed de novo and defined as the absence of symptoms, resumption of usual daily activities, and return to the previous state of health prior to the illness, using a 5-point Likert scale, and was endorsed. CONCLUSIONS: The coronavirus disease 2019 core outcome set recommended core outcome measures have content validity and are considered the most feasible and acceptable among existing measures. Implementation of the core outcome measures in trials in coronavirus disease 2019 will ensure consistency and relevance of the evidence to inform decision-making and care of patients with coronavirus disease 2019.

Dietary Potassium Intake and All-Cause Mortality in Adults Treated with Hemodialysis

Abstract: Background and objectives Dietary potassium restriction in people receiving maintenance hemodialysis is standard practice and is recommended in guidelines, despite a lack of evidence. We aimed to assess the association between dietary potassium intake and mortality and whether hyperkalemia mediates this association. Design, setting, participants, & measurements A total of 8043 adults undergoing maintenance hemodialysis in Europe and South America were included in the DIETary intake, death and hospitalization in adults with end-stage kidney disease treated with HemoDialysis (DIET-HD) study. We measured baseline potassium intake from the Global Allergy and Asthma European Network food frequency questionnaire and performed time-to-event and mediation analyses. Results The median potassium intake at baseline was 3.5 (interquartile range, 2.5–5.0) g/d. During a median follow-up of 4.0 years (25,890 person-years), we observed 2921 (36%) deaths. After adjusting for baseline characteristics, including cardiac disease and food groups, dietary potassium intake was not associated with all-cause mortality (per 1 g/d higher dietary potassium intake: hazard ratio, 1.00; 95% confidence interval [95% CI], 0.95 to 1.05). A mediation analysis showed no association of potassium intake with mortality, either through or independent of serum potassium (hazard ratio, 1.00; 95% CI, 1.00 to 1.00 and hazard ratio, 1.01; 95% CI, 0.96 to 1.06, respectively). Potassium intake was not significantly associated with serum levels (0.03; 95% CI, −0.01 to 0.07 mEq/L per 1 g/d higher dietary potassium intake) or the prevalence of hyperkalemia (≥6.0 mEq/L) at baseline (odds ratio, 1.11; 95% CI, 0.89 to 1.37 per 1 g/d higher dietary potassium intake). Hyperkalemia was associated with cardiovascular death (hazard ratio, 1.23; 95% CI, 1.03 to 1.48). Conclusions Higher dietary intake of potassium is not associated with hyperkalemia or death in patients treated with hemodialysis.

Dietary intake in adults on hemodialysis compared with guideline recommendations

Abstract: Clinical practice guidelines of dietary management are designed to promote a balanced diet and maintain health in patients undergoing haemodialysis but they may not reflect patients’ preferences. We aimed to investigate the consistency between the dietary intake of patients on maintenance haemodialysis and guideline recommendations. Cross-sectional analysis of the DIET-HD study, which included 6,906 adults undergoing haemodialysis in 10 European countries. Dietary intake was determined using the Global Allergy and Asthma European Network (GA2LEN) Food Frequency Questionnaire (FFQ), and compared with the European Best Practice Guidelines. Consistency with guidelines was defined as achieving the minimum daily recommended intake for energy (≥ 30 kcal/kg) and protein (≥ 1.1 g/kg), and not exceeding the maximum recommended daily intake for phosphate (≤ 1000 mg), potassium (≤ 2730 mg), sodium (≤ 2300 mg) and calcium (≤ 800 mg). Overall, patients’ dietary intakes of phosphate and potassium were infrequently consistent with guidelines (consistent in 25% and 25% of patients, respectively). Almost half of the patients reported that energy (45%) and calcium intake (53%) was consistent with the guidelines, while the recommended intake of sodium and protein was consistent in 85% and 67% of patients, respectively. Results were similar across all participating countries. Intake was consistent with all six guideline recommendations in only 1% of patients. Patients on maintenance haemodialysis usually have a dietary intake which is inconsistent with current recommendations, especially for phosphate and potassium.

Patient-reported outcome measures for pain in autosomal dominant polycystic kidney disease: A systematic review

Abstract: Pain is a common symptom in people with autosomal dominant polycystic kidney disease (ADPKD), but it is assessed and reported inconsistently in research, and the validity of the measures remain uncertain. The aim of this study was to identify the characteristics, content, and psychometric properties of measures for pain used in ADPKD. We conducted a systematic review including all trials and observational studies that reported pain in people with ADPKD. Items from all measures were categorized into content and measurement dimensions of pain. We assessed the general characteristics and psychometric properties of all measures. 118 studies, we identified 26 measures: 12 (46%) measures were developed for a non-ADPKD population, 1 (4%) for chronic kidney disease, 2 (8%) for polycystic liver disease and 11 (42%) specifically for ADPKD. Ten anatomical sites were included, with the lower back the most common (10 measures [39%]), four measurement dimensions (intensity (23 [88%]), frequency (3 [12%]), temporality (2 [8%]), and sensory (21 [81%]), two pain types, nociceptive including visceral (15 [58%]) and somatic (5 [20%]), and neuropathic (2 [8%]), and twelve impact dimensions, where the most frequent was work (5 [31%]). The validation data for the measures were variable and only the ADPKD Impact Scale reported all psychometric domains. The measures for pain in ADPKD varied in terms of content and length, and most had not been validated in ADPKD. A standardized psychometrically robust measure that captures patient-important dimensions of pain is needed to evaluate and manage this debilitating complication of ADPKD.

Establishing a core outcome measure for pain in patients with autosomal dominant polycystic kidney disease: a consensus workshop report

Abstract: Abstract Background Pain is the highest prioritized patient-reported outcome in people with autosomal dominant polycystic kidney disease (ADPKD) but remains infrequently and inconsistently measured in clinical trials and poorly managed in clinical settings. A recently completed systematic review of pain in ADPKD identified 26 different outcome measures. None of these measures were considered appropriate as a core outcome measure due to the lack of patient-important dimensions, inadequate content, relatively long duration of completion time and limited evidence to support psychometric robustness. Methods We convened an international Standardized Outcomes in Nephrology–Polycystic Kidney Disease consensus workshop involving 21 patients/caregivers and 40 health professionals (clinicians, nurses, researchers, policy makers and industry representatives) from 18 countries to discuss the identification or development of a core outcome measure for pain. Results Four themes were identified highlighting fundamental issues for the measurement of pain in ADPKD: distressing and disrupting life participation; variability and ambiguity in defining pain; stigma, frustration and adaptation to pain; and ensuring validity and feasibility of pain measures. Conclusions Existing measures were found to be insufficient in capturing pain as a core outcome and there was consensus on the need for a new validated measure that is simple, succinct and addresses the impact of pain on life participation. This measure will facilitate the appropriate prioritization of pain in all trials and guide clinical decision making in people with ADPKD.

Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial

Abstract: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63–1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41–2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62–2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02–1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. NCT01457001