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JAMAMetformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is... (Review)
Review
IMPORTANCE
Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.
OBJECTIVE
To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.
EVIDENCE ACQUISITION
In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.
RESULTS
Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100,000 person-years to 10 per 100,000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus--use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.
CONCLUSIONS AND RELEVANCE
Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.
Topics: Acidosis, Lactic; Contraindications; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic; Risk
PubMed: 25536258
DOI: 10.1001/jama.2014.15298 -
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 Physiology. Renal... Dec 2016Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the... (Review)
Review
Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the normal range and becoming almost universal in those who reach the end stage of kidney failure. The skeletal muscle represents the primary site of IR in CKD, and alterations at sites beyond the insulin receptor are recognized as the main defect underlying IR in this condition. Estimates of IR based on fasting insulin concentration are easier and faster but may not be adequate in patients with CKD because renal insufficiency reduces insulin catabolism. The hyperinsulinemic euglycemic clamp is the gold standard for the assessment of insulin sensitivity because this technique allows a direct measure of skeletal muscle sensitivity to insulin. The etiology of IR in CKD is multifactorial in nature and may be secondary to disturbances that are prominent in renal diseases, including physical inactivity, chronic inflammation, oxidative stress, vitamin D deficiency, metabolic acidosis, anemia, adipokine derangement, and altered gut microbiome. IR contributes to the progression of renal disease by worsening renal hemodynamics by various mechanisms, including activation of the sympathetic nervous system, sodium retention, and downregulation of the natriuretic peptide system. IR has been solidly associated with intermediate mechanisms leading to cardiovascular (CV) disease in CKD including left ventricular hypertrophy, vascular dysfunction, and atherosclerosis. However, it remains unclear whether IR is an independent predictor of mortality and CV complications in CKD. Because IR is a modifiable risk factor and its reduction may lower CV morbidity and mortality, unveiling the molecular mechanisms responsible for the pathogenesis of CKD-related insulin resistance is of importance for the identification of novel therapeutic targets aimed at reducing the high CV risk of this condition.
Topics: Disease Progression; Glucose Clamp Technique; Humans; Inflammation; Insulin Resistance; Oxidative Stress; Renal Insufficiency, Chronic; Vitamin D Deficiency
PubMed: 27707707
DOI: 10.1152/ajprenal.00340.2016 -
Actas Urologicas Espanolas May 2023Urine contact with the mucosa of the urinary diversion (UD) after radical cystectomy (RC) produces different ion exchanges that favor the development of metabolic... (Review)
Review
Urine contact with the mucosa of the urinary diversion (UD) after radical cystectomy (RC) produces different ion exchanges that favor the development of metabolic acidosis (MA). This phenomenon is a frequent cause of hospital readmission and short/long-term complications. We performed a systematic review of MA in RCs with ileal UD, analyzing its prevalence, diagnosis, risk factors and treatment. We systematically searched Pubmed® and Cochrane Library for original articles published before May 2022 according to PRISMA guidelines. A total of 421 articles were identified. We selected 25 studies that met the inclusion criteria involving 5811 patients. Obtaining precise data on the prevalence of MA is difficult, largely due to the heterogeneity of the diagnostic criteria used given the diversity of studies analyzed. Development of MA is multifactorial. In the early period, MA is more prevalent in patients with UD with longer ileal segments, better urinary continence, and impaired renal function. Age and diabetes are risk factors associated with MA in later periods. MA is the most common cause of second or more hospital readmissions. Prophylaxis with oral bicarbonate for three months in patients at risk could improve these results. Although MA after ileal UD is a well-known condition, this review highlights the need to implement homogeneous criteria for the diagnosis, follow-up, and treatment, in addition to protocolizing prevention/prophylaxis strategies in patients at risk.
Topics: Humans; Cystectomy; Urinary Bladder Neoplasms; Urinary Bladder; Urinary Diversion; Acidosis
PubMed: 36427800
DOI: 10.1016/j.acuroe.2022.11.005 -
The Cochrane Database of Systematic... Jul 2017Non-invasive ventilation (NIV) with bi-level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-invasive ventilation (NIV) with bi-level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory failure (AHRF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
OBJECTIVES
To compare the efficacy of NIV applied in conjunction with usual care versus usual care involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The aim of this review is to update the evidence base with the goals of supporting clinical practice and providing recommendations for future evaluation and research.
SEARCH METHODS
We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and PsycINFO, and through handsearching of respiratory journals and meeting abstracts. This update to the original review incorporates the results of database searches up to January 2017.
SELECTION CRITERIA
All randomised controlled trials that compared usual care plus NIV (BiPAP) versus usual care alone in an acute hospital setting for patients with AECOPD due to AHRF were eligible for inclusion. AHRF was defined by a mean admission pH < 7.35 and mean partial pressure of carbon dioxide (PaCO) > 45 mmHg (6 kPa). Primary review outcomes were mortality during hospital admission and need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in arterial blood gases.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the selection criteria to determine study eligibility, performed data extraction, and determined risk of bias in accordance with Cochrane guidelines. Review authors undertook meta-analysis for data that were both clinically and statistically homogenous, and analysed data as both one overall pooled sample and according to two predefined subgroups related to exacerbation severity (admission pH between 7.35 and 7.30 vs below 7.30) and NIV treatment setting (intensive care unit-based vs ward-based). We reported results for mortality, need for endotracheal intubation, and hospital length of stay in a 'Summary of findings' table and rated their quality in accordance with GRADE criteria.
MAIN RESULTS
We included in the review 17 randomised controlled trials involving 1264 participants. Available data indicate that mean age at recruitment was 66.8 years (range 57.7 to 70.5 years) and that most participants (65%) were male. Most studies (12/17) were at risk of performance bias, and for most (14/17), the risk of detection bias was uncertain. These risks may have affected subjective patient-reported outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.Use of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N = 17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality owing to uncertainty regarding risk of bias for several studies. Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome. NIV use was also associated with reduced length of hospital stay (mean difference (MD) -3.39 days, 95% CI -5.93 to -0.85; N = 10 studies), reduced incidence of complications (unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of oxygen (PaO) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one hour. A trend towards improvement in PaCO was observed, but this finding was not statistically significant (MD -4.62 mmHg, 95% CI -11.05 to 1.80 mmHg; N = 8 studies). Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the NIV group than in the usual care group). Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of NIV on PaCO. Treatment intolerance was significantly greater in the NIV group than in the usual care group (risk difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis showed a non-significant trend towards reduction in dyspnoea with NIV compared with usual care (standardised mean difference (SMD) -0.16, 95% CI -0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between-group differences.
AUTHORS' CONCLUSIONS
Data from good quality randomised controlled trials show that NIV is beneficial as a first-line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD). The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH < 7.30), and when NIV is applied within the intensive care unit (ICU) or ward setting.
Topics: Adult; Disease Progression; Humans; Noninvasive Ventilation; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Respiratory Insufficiency
PubMed: 28702957
DOI: 10.1002/14651858.CD004104.pub4 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2010Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut... (Review)
Review
INTRODUCTION
Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome.
METHODS
We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included "colchicine" and "poisoning" or "overdose" or "toxicity" or "intoxication."
TOXICOKINETICS
Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. THERAPEUTIC AND TOXIC DOSES: The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.
DRUG INTERACTIONS
CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy.
MECHANISMS OF TOXICITY
Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation.
CLINICAL FEATURES
Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness.
DIAGNOSIS
History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia).
MANAGEMENT
Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available.
CONCLUSION
Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adult; Charcoal; Clarithromycin; Clinical Trials as Topic; Colchicine; Colony-Stimulating Factors; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Familial Mediterranean Fever; Female; Granulocyte Colony-Stimulating Factor; Humans; Male
PubMed: 20586571
DOI: 10.3109/15563650.2010.495348 -
The Cochrane Database of Systematic... Jan 2016Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it is not uncommon in some people with type 2 diabetes. The treatment of DKA is traditionally accomplished by the administration of intravenous infusion of regular insulin that is initiated in the emergency department and continued in an intensive care unit or a high-dependency unit environment. It is unclear whether people with DKA should be treated with other treatment modalities such as subcutaneous rapid-acting insulin analogues.
OBJECTIVES
To assess the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis.
SEARCH METHODS
We identified eligible trials by searching MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library. We searched the trials registers WHO ICTRP Search Portal and ClinicalTrials.gov. The date of last search for all databases was 27 October 2015. We also examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors.
SELECTION CRITERIA
We included trials if they were RCTs comparing subcutaneous rapid-acting insulin analogues versus standard intravenous infusion in participants with DKA of any age or sex with type 1 or type 2 diabetes, and in pregnant women.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I² statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate.
MAIN RESULTS
Five trials randomised 201 participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). The criteria for DKA were consistent with the American Diabetes Association criteria for mild or moderate DKA. The underlying cause of DKA was mostly poor compliance with diabetes therapy. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Four trials evaluated the effects of the rapid-acting insulin analogue lispro, and one the effects of the rapid-acting insulin analogue aspart. The mean follow-up period as measured by mean hospital stay ranged between two and seven days. Overall, risk of bias of the evaluated trials was unclear in many domains and high for performance bias for the outcome measure time to resolution of DKA.No deaths were reported in the included trials (186 participants; 3 trials; moderate- (insulin lispro) to low-quality evidence (insulin aspart)). There was very low-quality evidence to evaluate the effects of subcutaneous insulin lispro versus intravenous regular insulin on the time to resolution of DKA: mean difference (MD) 0.2 h (95% CI -1.7 to 2.1); P = 0.81; 90 participants; 2 trials. In one trial involving children with DKA, the time to reach a glucose level of 250 mg/dL was similar between insulin lispro and intravenous regular insulin. There was very low-quality evidence to evaluate the effects of subcutaneous insulin aspart versus intravenous regular insulin on the time to resolution of DKA: MD -1 h (95% CI -3.2 to 1.2); P = 0.36; 30 participants; 1 trial. There was low-quality evidence to evaluate the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin on hypoglycaemic episodes: 6 of 80 insulin lispro-treated participants compared with 9 of 76 regular insulin-treated participants reported hypoglycaemic events; risk ratio (RR) 0.59 (95% CI 0.23 to 1.52); P = 0.28; 156 participants; 4 trials. For insulin aspart compared with regular insulin, RR for hypoglycaemic episodes was 1.00 (95% CI 0.07 to 14.55); P = 1.0; 30 participants; 1 trial; low-quality evidence. Socioeconomic effects as measured by length of mean hospital stay for insulin lispro compared with regular insulin showed a MD of -0.4 days (95% CI -1 to 0.2); P = 0.22; 90 participants; 2 trials; low-quality evidence and for insulin aspart compared with regular insulin 1.1 days (95% CI -3.3 to 1.1); P = 0.32; low-quality evidence. Data on morbidity were limited, but no specific events were reported for the comparison of insulin lispro with regular insulin. No trial reported on adverse events other than hypoglycaemic episodes, and no trial investigated patient satisfaction.
AUTHORS' CONCLUSIONS
Our review, which provided mainly data on adults, suggests on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA.
Topics: Adult; Child; Diabetic Ketoacidosis; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Short-Acting; Randomized Controlled Trials as Topic; Young Adult
PubMed: 26798030
DOI: 10.1002/14651858.CD011281.pub2 -
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 -
American Journal of Perinatology Aug 2017Risk factors for placental abruption have changed, but there has not been an updated systematic review investigating outcomes. We searched PubMed, EMBASE, Web of... (Review)
Review
Risk factors for placental abruption have changed, but there has not been an updated systematic review investigating outcomes. We searched PubMed, EMBASE, Web of Science, SCOPUS, and CINAHL for publications from January 1, 2005 through December 31, 2016. We reviewed English-language publications reporting estimated incidence and/or risk factors for maternal, labor, delivery, and perinatal outcomes associated with abruption. We excluded case studies, conference abstracts, and studies that lacked a referent/comparison group or did not clearly characterize placental abruption. A total of 123 studies were included. Abruption was associated with elevated risk of cesarean delivery, postpartum hemorrhage and transfusion, preterm birth, intrauterine growth restriction or low birth weight, perinatal mortality, and cerebral palsy. Additional maternal outcomes included relaparotomy, hysterectomy, sepsis, amniotic fluid embolism, venous thromboembolism, acute kidney injury, and maternal intensive care unit admission. Additional perinatal outcomes included acidosis, encephalopathy, severe respiratory disorders, necrotizing enterocolitis, acute kidney injury, need for resuscitation, chronic lung disease, infant death, and epilepsy. Few studies examined outcomes beyond the initial birth period, but there is evidence that both mother and child are at risk of additional adverse outcomes. There was also considerable variation in, or absence of, the reporting of abruption definitions.
Topics: Abruptio Placentae; Asphyxia Neonatorum; Blood Transfusion; Cerebral Palsy; Cesarean Section; Female; Fetal Growth Retardation; Humans; Hypoxia, Brain; Infant, Low Birth Weight; Infant, Newborn; Maternal Mortality; Perinatal Mortality; Postpartum Hemorrhage; Pregnancy; Premature Birth; Recurrence; Stillbirth
PubMed: 28329897
DOI: 10.1055/s-0037-1599149 -
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