-
Lancet (London, England) Nov 2022Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.
METHODS
We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.
FINDINGS
We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.
INTERPRETATION
In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.
FUNDING
UK Medical Research Council and Kidney Research UK.
Topics: Humans; Adult; Adolescent; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2; Kidney; Acute Kidney Injury; Renal Insufficiency, Chronic; Heart Failure; Ketosis; Disease Progression; Glucose; Sodium; Randomized Controlled Trials as Topic
PubMed: 36351458
DOI: 10.1016/S0140-6736(22)02074-8 -
Kidney & Blood Pressure Research 2020The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the...
BACKGROUND
The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician's perspective.
SUMMARY
We performed a systematic search on PubMed, applying the following search terms: "acute metabolic acidosis," "lactic acidosis," "metformin" AND "acidosis," "unbalanced solutions" AND "acidosis," "bicarbonate" AND "acidosis" AND "outcome," "acute metabolic acidosis" AND "management," and "acute metabolic acidosis" AND "renal replacement therapy (RRT)/dialysis." The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.
Topics: Acidosis; Acidosis, Lactic; Acute Disease; Animals; Bicarbonates; Disease Management; Electrolytes; Humans; Hypoglycemic Agents; Metformin
PubMed: 32663831
DOI: 10.1159/000507813 -
Journal of Medical Virology Nov 2022Viral infections may increase the risk of developing type 1 diabetes (T1D), and recent reports suggest that Coronavirus Disease 2019 (COVID-19) might have increased the... (Meta-Analysis)
Meta-Analysis Review
Viral infections may increase the risk of developing type 1 diabetes (T1D), and recent reports suggest that Coronavirus Disease 2019 (COVID-19) might have increased the incidence of pediatric T1D and/or diabetic ketoacidosis (DKA). Therefore, this meta-analysis aims to estimate the risk of global pediatric new-onset T1D, DKA, and severe DKA before and after the COVID-19 pandemic. A systematic search of MEDLINE/PubMed, CINAHL, Scopus, and EMBASE was conducted for articles published up to March 2022. A random-effects meta-analysis was performed to compare the relative risk of T1D and DKA among pediatric patients with T1D between the COVID-19 pre-pandemic and pandemic periods. We also compared glucose and HbA1c values in children who were newly diagnosed with T1D before and after the COVID-19 pandemic. The global incidence rate of T1D in the 2019 period was 19.73 per 100 000 children and 32.39 per 100 000 in the 2020 period. Compared with pre-COVID-19 pandemic, the number of worldwide pediatric new-onset T1D, DKA, and severe DKA during the first year of the COVID-19 pandemic increased by 9.5%, 25%, and 19.5%, respectively. Compared with pre-COVID-19 pandemic levels, the median glucose, and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic increased by 6.43% and 6.42%, respectively. The COVID-19 pandemic has significantly increased the risk of global pediatric new-onset T1D, DKA, and severe DKA. Moreover, higher glucose and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic mandates targeted measures to raise public and physician awareness.
Topics: COVID-19; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glucose; Glycated Hemoglobin; Humans; Incidence; Pandemics
PubMed: 35831242
DOI: 10.1002/jmv.27996 -
Current Diabetes Reports Aug 2021To assess the pleiotropic effects of ketogenic diets (KD) on glucose control, changes in medication, and weight loss in individuals with type 2 diabetes, and to evaluate... (Review)
Review
To assess the pleiotropic effects of ketogenic diets (KD) on glucose control, changes in medication, and weight loss in individuals with type 2 diabetes, and to evaluate its practical feasibility RECENT FINDINGS: KD results in improved HbA1c already after 3 weeks, and the effect seems to persist for at least 1 year. This is associated with a reduction in glucose-lowering medications. The weight loss observed after a short time period seems to be maintained with a long-term diet. Adequate support (supportive psychological counseling, enhancing positive affectivity, reinforcing mindful eating) is necessary to achieve a benefit and to assure adherence. Despite the documented decrease in HbA1, a definitive causal effect of KD remains to be proven. KD should be performed under strict medical supervision. Future research should clarify how compliance can be maximized and how ketosis can be optimally monitored.
Topics: Diabetes Mellitus, Type 2; Diet, Carbohydrate-Restricted; Diet, Ketogenic; Humans; Ketosis; Weight Loss
PubMed: 34448957
DOI: 10.1007/s11892-021-01399-z -
Pharmacotherapy Sep 2019Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are...
Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are diagnoses of exclusion and have the potential to be overlooked. The purposes of this systematic review are to identify published reports of medication-induced lactate level elevations to aid clinicians in diagnosing and comprehending the underlying mechanism of this rare adverse drug effect and to provide management strategies. The PubMed database was searched for case reports, case series, retrospective studies, and prospective studies describing cases of medication-induced lactate level elevation, including lactic acidosis and hyperlactatemia, published between January 1950 and June 2017. A standardized search strategy was used, and the articles identified underwent two rounds of independent evaluation by two reviewers to assess for inclusion. Articles were included if they described at least one patient older than 12 years with hyperlactatemia or lactic acidosis caused by a medication with United States Food and Drug Administration (FDA) approval and if alternative etiologies for an elevated lactate level were ruled out. Metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded since the pathophysiology and incidence of lactic acidosis have been well established for these agents. Overall, 1918 articles were identified, and 101 met inclusion criteria. A total of 286 patients experienced medication-induced lactate level elevations, from which 59 unique medications were identified. The most commonly identified agents were epinephrine and albuterol. Medication-induced lactate level elevation was classified as lactic acidosis (64.0%), hyperlactatemia (31.1%), or not specified (4.9%). The doses ingested included FDA-labeled doses (86%), intentional overdoses (10.8%), or prescribed doses exceeding the FDA-labeled dose (3.1%). Medications were continued without a change (40.8%), were permanently discontinued (34.4%), were continued with a dosage reduction (11.6%), or were initially withheld then resumed after lactate level normalized (2.9%); medication management for the remaining 10.0% was not reported. Forty-six patients died (16%). Six deaths were attributed by treating clinicians to be secondary to medication-induced lactic acidosis. Management strategies were heterogeneous, and treatment included supportive care, exogenous bicarbonate therapy, medication specific antidotes, and decontamination strategies. Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations. Pharmacists are members of the health care team that are well positioned to serve as experts in the diagnosis and management of medication-induced lactate level elevations.
Topics: Acidosis, Lactic; Dose-Response Relationship, Drug; Drug Overdose; Humans; Hyperlactatemia; Prescription Drug Misuse; Prescription Drugs; United States
PubMed: 31361914
DOI: 10.1002/phar.2316 -
JAMA Network Open Jun 2023There are reports of increasing incidence of pediatric diabetes since the onset of the COVID-19 pandemic. Given the limitations of individual studies that examine this... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
There are reports of increasing incidence of pediatric diabetes since the onset of the COVID-19 pandemic. Given the limitations of individual studies that examine this association, it is important to synthesize estimates of changes in incidence rates.
OBJECTIVE
To compare the incidence rates of pediatric diabetes during and before the COVID-19 pandemic.
DATA SOURCES
In this systematic review and meta-analysis, electronic databases, including Medline, Embase, the Cochrane database, Scopus, and Web of Science, and the gray literature were searched between January 1, 2020, and March 28, 2023, using subject headings and text word terms related to COVID-19, diabetes, and diabetic ketoacidosis (DKA).
STUDY SELECTION
Studies were independently assessed by 2 reviewers and included if they reported differences in incident diabetes cases during vs before the pandemic in youths younger than 19 years, had a minimum observation period of 12 months during and 12 months before the pandemic, and were published in English.
DATA EXTRACTION AND SYNTHESIS
From records that underwent full-text review, 2 reviewers independently abstracted data and assessed the risk of bias. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Eligible studies were included in the meta-analysis and analyzed with a common and random-effects analysis. Studies not included in the meta-analysis were summarized descriptively.
MAIN OUTCOMES AND MEASURES
The primary outcome was change in the incidence rate of pediatric diabetes during vs before the COVID-19 pandemic. The secondary outcome was change in the incidence rate of DKA among youths with new-onset diabetes during the pandemic.
RESULTS
Forty-two studies including 102 984 incident diabetes cases were included in the systematic review. The meta-analysis of type 1 diabetes incidence rates included 17 studies of 38 149 youths and showed a higher incidence rate during the first year of the pandemic compared with the prepandemic period (incidence rate ratio [IRR], 1.14; 95% CI, 1.08-1.21). There was an increased incidence of diabetes during months 13 to 24 of the pandemic compared with the prepandemic period (IRR, 1.27; 95% CI, 1.18-1.37). Ten studies (23.8%) reported incident type 2 diabetes cases in both periods. These studies did not report incidence rates, so results were not pooled. Fifteen studies (35.7%) reported DKA incidence and found a higher rate during the pandemic compared with before the pandemic (IRR, 1.26; 95% CI, 1.17-1.36).
CONCLUSIONS AND RELEVANCE
This study found that incidence rates of type 1 diabetes and DKA at diabetes onset in children and adolescents were higher after the start of the COVID-19 pandemic than before the pandemic. Increased resources and support may be needed for the growing number of children and adolescents with diabetes. Future studies are needed to assess whether this trend persists and may help elucidate possible underlying mechanisms to explain temporal changes.
Topics: Child; Humans; Incidence; Diabetes Mellitus, Type 1; Pandemics; Diabetes Mellitus, Type 2; COVID-19; Diabetic Ketoacidosis
PubMed: 37389869
DOI: 10.1001/jamanetworkopen.2023.21281 -
Diabetologia Dec 2022Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have... (Meta-Analysis)
Meta-Analysis Review
AIMS/HYPOTHESIS
Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have been reported. The risk/benefit ratio of SGLT2i remains unquantified. We aimed to provide an estimation of their risk/benefit ratio in individuals with type 2 diabetes.
METHODS
We conducted a systematic review (MEDLINE, up to 14 September 2021) and meta-analysis. We included randomised CVOTs assessing SGLT2i in individuals with type 2 diabetes with or without other diseases. We used the Cochrane 'Risk of bias' assessment tool. The primary outcomes were overall mortality, major adverse cardiovascular events (MACE), hospitalisation for heart failure (HHF), end-stage renal disease (ESRD), amputation, diabetic ketoacidosis (DKA) and reported genital infections. For each outcome, we estimated the incidence rate ratio (IRR) with a 95% CI; we then computed the number of events expected spontaneously and with SGLT2i.
RESULTS
A total of 46,969 participants from five double-blind, placebo-controlled international trials (weighted mean follow-up 3.5 years) were included. The prevalence of previous CVD ranged from 40.6% to 99.2%. The definition of reported genital infections ranged from 'genital mycotic infection' to 'genital infections that led to discontinuation of the trial regimen or were considered to be serious adverse events'. The number of included studies for each outcomes was five. The use of SGLT2i decreased the risk of all-cause death (IRR 0.86 [95% CI 0.78, 0.95]), MACE (IRR 0.91 [95% CI 0.86, 0.96]), HHF (IRR 0.69 [95% CI 0.62, 0.76]) and ESRD (IRR 0.67 [95% CI 0.53, 0.84]), and increased the risk of DKA (IRR 2.59 [95% CI 1.57, 4.27]) and genital infection (IRR 3.50 [95% CI 3.09, 3.95]) but not of amputation (IRR 1.23 [95% CI 1.00, 1.51]). For 1000 individuals treated over 3.5 years, SGLT2i are expected, on average, to decrease the number of deaths from 70 to 61, to prevent nine MACE, 11 HHF and two cases of ESRD, while inducing two DKA occurrences and 36 genital infections; 778 individuals are expected to avoid all the following outcomes: MACE, HHF, ESRD, amputation, DKA and genital infection.
CONCLUSIONS/INTERPRETATION
Our study is limited to aggregate data. In a population of individuals with type 2 diabetes and a high CVD risk, the cardiovascular and renal benefits of SGLT2i remain substantial despite the risk of DKA and even the hypothetical risk of amputation.
TRIAL REGISTRATION
OSF Registries: https://doi.org/10.17605/OSF.IO/J3R7Y FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Heart Failure; Risk Assessment; Kidney Failure, Chronic; Cardiovascular Diseases; Randomized Controlled Trials as Topic
PubMed: 35925319
DOI: 10.1007/s00125-022-05773-8 -
American Journal of Obstetrics and... May 2023This study aimed to reassess the effect of prophylactic transcervical amnioinfusion for intrapartum meconium-stained amniotic fluid on meconium aspiration syndrome and... (Meta-Analysis)
Meta-Analysis Review
Intrapartum amnioinfusion reduces meconium aspiration syndrome and improves neonatal outcomes in patients with meconium-stained fluid: a systematic review and meta-analysis.
OBJECTIVE
This study aimed to reassess the effect of prophylactic transcervical amnioinfusion for intrapartum meconium-stained amniotic fluid on meconium aspiration syndrome and other adverse neonatal and maternal outcomes.
DATA SOURCES
From inception to November 2021, a systematic search of the literature was performed in PubMed, Embase, Web of Science, and Scopus databases and gray literature sources.
STUDY ELIGIBILITY CRITERIA
We identified randomized controlled trials of patients with intrapartum moderate to thick meconium-stained amniotic fluid that evaluated the effect of amnioinfusion on adverse neonatal and maternal outcomes.
METHODS
Of note, 2 reviewers independently abstracted data and gauged study quality by assigning a modified Jadad score. Meconium aspiration syndrome constituted the primary outcome. The secondary outcomes were meconium below the cords, Apgar scores of <7 at 5 minutes, neonatal acidosis, cesarean delivery, cesarean delivery for fetal heart rate abnormalities, neonatal intensive care unit admission, and postpartum endometritis. This study calculated the odds ratios with 95% confidence intervals for categorical outcomes and weighted mean differences with 95% confidence intervals for continuous outcomes.
RESULTS
A total of 24 randomized studies with 5994 participants met the inclusion criteria. The overall odds of meconium aspiration syndrome was reduced by 67% in the amnioinfusion group (pooled odds ratio, 0.33; 95% confidence interval, 0.21-0.51). Except for postpartum endometritis, amnioinfusion was associated with a significant reduction in all secondary outcomes.
CONCLUSION
Our study found that the use of intrapartum amnioinfusion in the setting of meconium-stained amniotic fluid significantly reduces the odds of meconium aspiration syndrome and other adverse neonatal outcomes.
Topics: Pregnancy; Female; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Meconium; Amnion; Endometritis; Obstetric Labor Complications; Sodium Chloride; Amniotic Fluid
PubMed: 37164492
DOI: 10.1016/j.ajog.2022.07.047 -
Archives of Disease in Childhood Nov 2022Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus, which may lead to significant morbidity and mortality. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes mellitus, which may lead to significant morbidity and mortality.
OBJECTIVES
To compare the safety and efficacy of liberalised versus conservative intravenous fluid regimens in the management of DKA in children.
DATA SOURCE AND STUDY SELECTION
Databases from inception to January 2022: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials were included. Only randomised controlled trials (RCTs) that included children aged under 18 years were assessed. Two reviewers performed data assessment and extraction.
DATA EXTRACTION AND SYNTHESIS
Three studies out of 1536 citations were included.
MAIN OUTCOMES
The time to the recovery from the DKA; the frequency of paeditric intensive care unit (PICU) admissions; development of brain oedema; reduction in Glasgow Coma Scale (GCS); development of acute kidney injury and all-cause mortality.
RESULTS
We included three RCTs (n=1457). No evidence of difference was noted in the GCS reduction (risk ratio (RR)=0.77, 95% CI 0.44 to 1.36) or development of brain oedema (RR=0.50, 95% CI 0.15 to 1.68). The time to recovery from DKA was longer in the conservative group (mean difference=1.42, 95% CI 0.28 to 2.56). Time to hospital discharge, adverse or serious adverse events were comparable in the two studied groups.
CONCLUSION
There is no evidence from this meta-analysis that rate of fluid administration has any effect on adverse neurological and other outcomes or length of hospital stay.
Topics: Child; Humans; Adolescent; Diabetic Ketoacidosis; Brain Edema; Length of Stay; Clinical Protocols; Glasgow Coma Scale; Diabetes Mellitus
PubMed: 35738870
DOI: 10.1136/archdischild-2022-324042 -
The Clinical Respiratory Journal Nov 2023Chronic obstructive pulmonary disease can lead to acute hypercapnic respiratory failure (AHRF), often treated using noninvasive ventilation (NIV). Emerging research... (Meta-Analysis)
Meta-Analysis Review
Chronic obstructive pulmonary disease can lead to acute hypercapnic respiratory failure (AHRF), often treated using noninvasive ventilation (NIV). Emerging research suggests the potential utility of high flow nasal cannula (HFNC) for AHRF. This systematic review and meta-analysis aimed to determine the effect of HFNC versus NIV on AHRF management. A search of electronic databases (CINAHL, MEDLINE, and Academic Search Complete), web sources, and trial registries was last conducted on 9 February 2023. Quality and risk of bias assessments were conducted. Meta-analyses were used to synthesise data. Seven randomised controlled trials were included. No statistically significant differences between HFNC and NIV were found within the following outcomes of interest: (i) correction of pCO2: standardised mean difference (SMD) = -0.16, 95% confidence interval (CI) (-0.34 to 0.02), p = 0.08; (ii) correction of pH: SMD = -0.05, 95% CI (-0.25 to 0.14), p = 0.59; (iii) correction of pO2: SMD = -0.15, 95% CI (-0.40 to 0.09), p = 0.22; (iv) intubation rates: risk ratio (RR) = 0.87, 95% CI (0.41 to 1.82), p = 0.71; (v) mortality rates: RR = 0.85, 95% CI (0.47 to 1.56), p = 0.61; and (vi) treatment switch: RR = 1.30, 95% CI (0.43 to 3.94), p = 0.64. More controlled trials with large sample sizes are required to investigate the management of AHRF of various aetiologies. HFNC may be used as a final exhaustive measure for COPD-related AHRF where NIV is not tolerated, and when it is not clinically indicated to extend to endotracheal intubation.
Topics: Humans; Noninvasive Ventilation; Cannula; Respiratory Insufficiency; Intubation, Intratracheal; Pulmonary Disease, Chronic Obstructive; Oxygen Inhalation Therapy
PubMed: 37700578
DOI: 10.1111/crj.13695