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Critical Care (London, England) Jan 2021Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical... (Meta-Analysis)
Meta-Analysis
Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.
BACKGROUND
Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation.
METHODS
We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.
RESULTS
Eleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94-1.09; P = 0.77; I = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23-1.63; P < 0.00001; I = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01-1.78; P = 0.04; I = 0%).
CONCLUSIONS
This meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.
Topics: Acute Kidney Injury; Critical Illness; Humans; Incidence; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Time Factors; Time-to-Treatment
PubMed: 33407756
DOI: 10.1186/s13054-020-03451-y -
Diabetes, Obesity & Metabolism Sep 2020To assess the effects of sodium-glucoseco-transporter-2 (SGLT2) inhibitors on diabetic ketoacidosis (DKA) in patients with type 2 diabetes. (Meta-Analysis)
Meta-Analysis
Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.
AIM
To assess the effects of sodium-glucoseco-transporter-2 (SGLT2) inhibitors on diabetic ketoacidosis (DKA) in patients with type 2 diabetes.
MATERIALS AND METHODS
We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to 13 June 2019 for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with control in patients with type 2 diabetes. Paired reviewers independently screened citations, assessed the risk of bias and extracted data. Peto's method was used as the primary approach to pool the effect of SGLT2 inhibitors on DKA. Sensitivity analyses with the alternative effect measure (risk ratio) or pooling method (Mantel-Haenszel), the use of continuity correction of 0.5 for zero-event trials or a generalized linear mixed model were conducted. Six preplanned subgroup analyses were performed to explore heterogeneity. The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence.
RESULTS
A total of 39 RCTs were included, involving 60 580 patients and 85 DKA events. SGLT2 inhibitors were statistically associated with an increased risk of DKA versus control (SGLT2 inhibitors: 62/34 961 [0.18%] vs. control: 23/25 211 [0.09%], Peto odds ratio [OR] 2.13, 95% confidence interval [CI] 1.38 to 3.27, I = 8%; RD 1.7 more events, 95% CI 0.6 more to 3.4 more events per 1000 over 5 years; high-quality evidence). Sensitivity analyses showed similar results. The subgroup analyses by mean age (interaction P = 0 .02) and length of follow-up (interaction P = 0 .03) showed a larger relative effect among older patients (aged ≥60 years) and those with longer use of SGLT2 inhibitors (>52 weeks).
CONCLUSIONS
High-quality evidence suggests that SGLT2 inhibitors may increase the risk of DKA in patients with type 2 diabetes. The apparent differences in treatment effects among patients of a different age or follow-up were probable, suggesting the advisability of caution in patients with long-term use of SGLT2 inhibitors or in older patients.
Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Glucose; Humans; Hypoglycemic Agents; Middle Aged; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 32364674
DOI: 10.1111/dom.14075 -
BMJ Open Feb 2019To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies.
DESIGN
We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs).
INTERVENTION
SGLT2 inhibitors, compared with placebo or active comparators.
PRIMARY OUTCOMES
Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations.
RESULTS
We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture.
CONCLUSIONS
Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear.
PROSPERO REGISTRATION NUMBER
CRD42016038715.
Topics: Acute Kidney Injury; Amputation, Surgical; Benzhydryl Compounds; Canagliflozin; Diabetic Ketoacidosis; Fractures, Bone; Glucosides; Humans; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Urinary Tract Infections
PubMed: 30813108
DOI: 10.1136/bmjopen-2018-022577 -
Rheumatology (Oxford, England) Dec 2015To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS.
OBJECTIVE
To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS.
METHODS
The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features.
RESULTS
The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ.
CONCLUSION
The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines.
Topics: Adult; Advisory Committees; Europe; Evidence-Based Medicine; Female; Humans; Joint Diseases; Kidney Diseases; Lung Diseases; Male; Middle Aged; Prevalence; Prognosis; Severity of Illness Index; Sjogren's Syndrome; Skin Diseases
PubMed: 26231345
DOI: 10.1093/rheumatology/kev200 -
Cureus Mar 2019The management of acid-base disorders always calls for precise diagnosis and treatment of the underlying disease. Sometimes additional means are necessary to combat... (Review)
Review
The management of acid-base disorders always calls for precise diagnosis and treatment of the underlying disease. Sometimes additional means are necessary to combat systemic acidity itself. In this systematic review, we discuss the concept and some specific aspects of bicarbonate therapy for critically ill patients with metabolic acidosis (i.e., patients with blood pH < 7.35). We conducted a systematic literature review of three online databases (PubMed, Google Scholar, and Cochrane) in November 2018 to validate usage of bicarbonate therapy for critically ill patients with metabolic acidosis. Twelve trials and case series were included in the final analysis, from which we assessed population, intervention, comparison, and outcome data. The current literature suggests limited benefit from bicarbonate therapy for patients with severe metabolic acidosis (pH < 7.1 and bicarbonate < 6 mEq/L). However, bicarbonate therapy does yield improvement in survival for patients with accompanying acute kidney injury.
PubMed: 31183278
DOI: 10.7759/cureus.4297 -
Cardiovascular Diabetology Mar 2022We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).
METHODS
We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).
RESULTS
A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion.
CONCLUSIONS
Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diabetic Nephropathies; Female; Heart Failure; Humans; Kidney; Male; Myocardial Infarction; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 35321742
DOI: 10.1186/s12933-022-01476-x -
Journal of Critical Care Jun 2019We aimed to assess the biochemical and physiological effects, clinical efficacy, and safety, of intravenous NaHCO3 therapy in critically ill patients with acute...
PURPOSE
We aimed to assess the biochemical and physiological effects, clinical efficacy, and safety, of intravenous NaHCO3 therapy in critically ill patients with acute metabolic acidosis.
METHODS
We conducted a scoping review concerning the biochemical and physiological effects of NaHCO3 (PART A), and a systematic review regarding clinical efficacy (PART B). We searched MEDLINE in Part A and MEDLINE, EMBASE, Cochrane, the National Institute of Health Clinical Trials Register, and the WHOICTRP for randomised controlled trials in Part B.
RESULTS
Twelve studies in Part A and two trials in Part B fulfilled the eligibility criteria. Intravenous NaHCO3 increased blood pH, base excess, serum bicarbonate, sodium, and PaCO2 during and after administration and decreased anion gap and potassium value. For clinical efficacy, only one study contributed to the effect estimate. The risk ratio (RR) for all-cause mortality was 0.83 (95% confidence interval, 0.68 to 1.02), and the risk of hypocalcaemia was increased in the bicarbonate group (RR 1.65, 95% confidence interval 1.09 to 2.50). There were inadequate data on hemodynamic indices.
CONCLUSIONS
Given the lack of data on the effects of intravenous NaHCO3 therapy to support its clinical use and the frequency of bicarbonate therapy, a program of investigation appears justified.
Topics: Acidosis; Beryllium; Critical Illness; Humans; Potassium; Sodium; Sodium Bicarbonate; Treatment Outcome
PubMed: 30852347
DOI: 10.1016/j.jcrc.2019.02.027 -
Age and Ageing Jan 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model.
RESULTS
We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis.
CONCLUSIONS
In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glycated Hemoglobin; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2; Frail Elderly; Heart Failure; Death; Glucose; Sodium
PubMed: 38287703
DOI: 10.1093/ageing/afad254 -
BJOG : An International Journal of... Mar 2017Umbilical cord lactate is one approach to measuring acidosis and intrapartum hypoxia, knowledge of which may be helpful for clinicians involved in the care of women and... (Review)
Review
BACKGROUND
Umbilical cord lactate is one approach to measuring acidosis and intrapartum hypoxia, knowledge of which may be helpful for clinicians involved in the care of women and newborns.
OBJECTIVE
To synthesise the evidence on accuracy of umbilical cord lactate in measuring acidosis and predicting poor neonatal outcome.
SEARCH STRATEGY
Studies published and unpublished between 1990 and 2014 from PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov were assessed.
SELECTION CRITERIA
Cross-sectional and randomised studies that assessed fetal acidosis (using lactate as the index test) with or without an assessment of neonatal outcome.
DATA COLLECTION AND ANALYSIS
Correlations between index and reference test(s) were recorded, as were the raw data to classify the predictive ability of umbilical lactate for neonatal outcomes. Meta-analysis of correlation was performed. We plotted estimates of the studies' observed sensitivities and specificities on Forest plots with 95% confidence intervals (CI). Where possible, we combined data using meta-analysis, applying the hierarchical summary receiver operating characteristics model and a bivariate model.
MAIN RESULTS
Twelve studies were included. Umbilical lactate correlated with pH [pooled effect size (ES) -0.650; 95% CI -0.663 to -0.637, P < 0.001], base excess (ES -0.710; 95% CI -0.721 to -0.699, P < 0.001), and Apgar scores at 5 minutes (ES 0.300; 95% 0.193-0.407, P < 0.001). Umbilical lactate had pooled sensitivity and specificity for predicting neonatal neurological outcome including hypoxic ischaemic encephalopathy of 69.7% (95% CI 23.8-94.4%) and 93% (95% CI 86.8-96.3%).
AUTHORS' CONCLUSION
Umbilical cord lactate is a clinically applicable, inexpensive and effective way to measure acidosis and is a tool that may be used in the assessment of neonatal outcome.
TWEETABLE ABSTRACT
Umbilical cord lactate: a clinically applicable, inexpensive, effective way to measure intrapartum acidosis.
Topics: Acidosis; Apgar Score; Female; Fetal Blood; Fetal Distress; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Lactic Acid; Pregnancy; Risk Assessment; Sensitivity and Specificity
PubMed: 27704703
DOI: 10.1111/1471-0528.14306 -
Pulmonology 2019Chronic Obstructive Pulmonary Disease (COPD) history is characterized by episodes of exacerbation of varying severity, featured by acute worsening of respiratory...
Chronic Obstructive Pulmonary Disease (COPD) history is characterized by episodes of exacerbation of varying severity, featured by acute worsening of respiratory symptoms, commonly precipitated by respiratory tract infection. The recent ERS/ATS clinical practice guidelines strongly recommend the application of non invasive ventilation (NIV) for patients with acute respiratory failure (ARF) leading to acute or acute-on-chronic respiratory acidosis (pH 7.35) and not for those patients with acute exacerbation of COPD (AECOPD) and hypercapnia who are not acidotic. In recent years, High-Flow through Nasal Cannula (HFNC) has been introduced in the clinical practice. We designed the present systematic review of the literature to assess all effects of HFNC use reported in exacerbated COPD patients. In this setting, HFNC is able to keep PaCO2 unmodified, while oxygenation slightly deteriorates as opposed to NIV. Furthermore, the work of breathing is reduced with HFNC by a similar extent to NIV, while it increases by 40-50% during conventional oxygen therapy (COT). HFNC is also reported to be more comfortable than COT and NIV. Despite these results, little and limited evidence for improved clinical outcomes is currently available.
Topics: Acidosis, Respiratory; Blood Gas Analysis; Disease Progression; Humans; Hypercapnia; Noninvasive Ventilation; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Respiratory Rate; Respiratory Therapy; Treatment Outcome; Work of Breathing
PubMed: 31591056
DOI: 10.1016/j.pulmoe.2019.08.001