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Frontiers in Endocrinology 2023The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUNDS
The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.
METHODS
This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.
RESULTS
Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.
CONCLUSION
In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fractures, Bone; Hypoglycemia; Hypovolemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37701900
DOI: 10.3389/fendo.2023.1238399 -
Maedica Dec 2023ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic...
ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic acidosis. A systematic review was conducted with the aim to evaluate the effect of STAN method compared with isolated CTG on perinatal and neonatal outcomes. A search of electronic databases (PubMed, Cochrane, Scopus) was conducted to identify randomized controlled trials (RCTs) in English language. Outcomes considered operative deliveries, fetal blood sampling (FBS), metabolic acidosis, perinatal and neonatal death, neonatal seizures, neonatal encephalopathy, transfer to the neonatal intensive care unit (NICU) and Apgar score. Seven RCTs were included in the present review. The first two RCTs showed that the combination of STAN and CTG was a better option than using CTG alone, because there was a documented reduction in the rate of operative deliveries due to fetal distress and metabolic acidosis. The following studies showed no statistically significant changes with the combination of methods, except from a reduction in FBS. The findings from the RCTs were inconclusive. Most studies did not demonstrate a superiority of the combination regarding operative deliveries and neonatal outcomes but there were many methodological differences between the trials.
PubMed: 38348066
DOI: 10.26574/maedica.2023.18.4.684 -
Journal of Cachexia, Sarcopenia and... Dec 2023Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass... (Meta-Analysis)
Meta-Analysis Review
Metabolic acidosis unfavourably influences the nutritional status of patients with non-dialysis dependent chronic kidney disease (CKD) including the loss of muscle mass and functionality, but the benefits of correction are uncertain. We investigated the effects of correcting metabolic acidosis on nutritional status in patients with CKD in a systematic review and meta-analysis. A search was conducted in MEDLINE and the Cochrane Library from inception to June 2023. Study selection, bias assessment, and data extraction were independently performed by two reviewers. The Cochrane risk of bias tool was used to assess the quality of individual studies. We applied random effects meta-analysis to obtain pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). We retrieved data from 12 intervention studies including 1995 patients, with a mean age of 63.7 ± 11.7 years, a mean estimated glomerular filtration rate of 29.8 ± 8.8 mL/min per 1.73 m , and 58% were male. Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo. The mean change in serum bicarbonate was +3.6 mEq/L in the intervention group and +0.4 mEq/L in the control group. Correcting metabolic acidosis significantly improved muscle mass assessed by mid-arm muscle circumference (SMD 0.35 [95% CI 0.16 to 0.54], P < 0.001) and functionality assessed with the sit-to-stand test (SMD -0.31 [95% CI -0.52 to 0.11], P = 0.003). We found no statistically significant effects on dietary protein intake, handgrip strength, serum albumin and prealbumin concentrations, and blood urea nitrogen. Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD.
Topics: Humans; Male; Middle Aged; Aged; Female; Dietary Proteins; Hand Strength; Renal Insufficiency, Chronic; Acidosis; Muscles
PubMed: 37728018
DOI: 10.1002/jcsm.13330 -
The Cochrane Database of Systematic... May 2023Although acute diarrhoea is a self-limiting disease, dehydration may occur in some children. Dehydration is the consequence of an increased loss of water and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although acute diarrhoea is a self-limiting disease, dehydration may occur in some children. Dehydration is the consequence of an increased loss of water and electrolytes (sodium, chloride, potassium, and bicarbonate) in liquid stools. When these losses are high and not replaced adequately, severe dehydration appears. Severe dehydration is corrected with intravenous solutions. The most frequently used solution for this purpose is 0.9% saline. Balanced solutions (e.g. Ringer's lactate) are alternatives to 0.9% saline and have been associated with fewer days of hospitalization and better biochemical outcomes. Available guidelines provide conflicting recommendations. It is unclear whether 0.9% saline or balanced intravenous fluids are most effective for rehydrating children with severe dehydration due to diarrhoea.
OBJECTIVES
To evaluate the benefits and harms of balanced solutions for the rapid rehydration of children with severe dehydration due to acute diarrhoea, in terms of time in hospital and mortality compared to 0.9% saline.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 4 May 2022.
SELECTION CRITERIA
We included randomized controlled trials in children with severe dehydration due to acute diarrhoea comparing balanced solutions, such as Ringer's lactate or Plasma-Lyte with 0.9% saline solution, for rapid rehydration.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. time in hospital and 2.
MORTALITY
Our secondary outcomes were 3. need for additional fluids, 4. total amount of fluids received, 5. time to resolution of metabolic acidosis, 6. change in and the final values of biochemical measures (pH, bicarbonate, sodium, chloride, potassium, and creatinine), 7. incidence of acute kidney injury, and 8.
ADVERSE EVENTS
We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
Characteristics of the included studies We included five studies with 465 children. Data for meta-analysis were available from 441 children. Four studies were conducted in low- and middle-income countries and one study in two high-income countries. Four studies evaluated Ringer's lactate, and one study evaluated Plasma-Lyte. Two studies reported the time in hospital, and only one study reported mortality as an outcome. Four studies reported final pH and five studies reported bicarbonate levels. Adverse events reported were hyponatremia and hypokalaemia in two studies each. Risk of bias All studies had at least one domain at high or unclear risk of bias. The risk of bias assessment informed the GRADE assessments. Primary outcomes Compared to 0.9% saline, the balanced solutions likely result in a slight reduction of the time in hospital (mean difference (MD) -0.35 days, 95% confidence interval (CI) -0.60 to -0.10; 2 studies; moderate-certainty evidence). However, the evidence is very uncertain about the effect of the balanced solutions on mortality during hospitalization in severely dehydrated children (risk ratio (RR) 0.33, 95% CI 0.02 to 7.39; 1 study, 22 children; very low-certainty evidence). Secondary outcomes Balanced solutions probably produce a higher increase in blood pH (MD 0.06, 95% CI 0.03 to 0.09; 4 studies, 366 children; low-certainty evidence) and bicarbonate levels (MD 2.44 mEq/L, 95% CI 0.92 to 3.97; 443 children, four studies; low-certainty evidence). Furthermore, balanced solutions likely reduces the risk of hypokalaemia after the intravenous correction (RR 0.54, 95% CI 0.31 to 0.96; 2 studies, 147 children; moderate-certainty evidence). Nonetheless, the evidence suggests that balanced solutions may result in no difference in the need for additional intravenous fluids after the initial correction; in the amount of fluids administered; or in the mean change of sodium, chloride, potassium, and creatinine levels.
AUTHORS' CONCLUSIONS
The evidence is very uncertain about the effect of balanced solutions on mortality during hospitalization in severely dehydrated children. However, balanced solutions likely result in a slight reduction of the time in the hospital compared to 0.9% saline. Also, balanced solutions likely reduce the risk of hypokalaemia after intravenous correction. Furthermore, the evidence suggests that balanced solutions compared to 0.9% saline probably produce no changes in the need for additional intravenous fluids or in other biochemical measures such as sodium, chloride, potassium, and creatinine levels. Last, there may be no difference between balanced solutions and 0.9% saline in the incidence of hyponatraemia.
Topics: Child; Humans; Bicarbonates; Creatinine; Dehydration; Diarrhea; Hypokalemia; Potassium; Potassium Chloride; Ringer's Lactate; Saline Solution; Sodium
PubMed: 37196992
DOI: 10.1002/14651858.CD013640.pub2 -
Research in Veterinary Science Aug 2023Laminitis is usually considered a consequence of digestive disorders that reduce ruminal pH. However, it is still not clear the direct relation between low ruminal pH...
Laminitis is usually considered a consequence of digestive disorders that reduce ruminal pH. However, it is still not clear the direct relation between low ruminal pH provoked by excessive fast-digesting carbohydrate ingestion and laminitis, considering indicators, signs, and diagnosis aspects. This study aimed to clarify the association between different clinical presentations of laminitis with ruminal acidosis provoked by diet using the systematic review methodology. Three electronic databases were used: ISI Web of Science, PubMed, and Scopus. A total of 339 manuscripts were identified and only 16 were included. Manuscripts were published between 2000 and 2021 in 11 different peer-reviewed journals. Fifteen studies confirmed the occurrence of ruminal acidosis. The main indicators used were ruminal pH and clinical signs, such as anorexia, depression, discomfort and diarrhea. Two of the studies that administered oligofructose to induce acidosis and acute laminitis did not observe clinical signs of laminitis, using lameness score or hooves' sensitivity as an indicator. Various diagnostic methods were used to describe laminitis, like thermography, hoof biopsy, sensitivity test, and visual inspection. Although the variety of laminitis indicators used in the included studies, we evidence the existence of an association between diet (high level of fast-digesting carbohydrates), ruminal acidosis, and acute laminitis, mostly in the short-term acidosis' induction protocols, but the mechanism of action is still not clear.
Topics: Animals; Cattle; Acidosis; Cattle Diseases; Dermatitis; Diet; Hydrogen-Ion Concentration; Rumen
PubMed: 37356405
DOI: 10.1016/j.rvsc.2023.06.001 -
Minerva Medica Aug 2021The antimicrobial trimethoprim is structurally related to potassium-sparing diuretics and may consequently lead to derangements in electrolyte and acid-base balance....
INTRODUCTION
The antimicrobial trimethoprim is structurally related to potassium-sparing diuretics and may consequently lead to derangements in electrolyte and acid-base balance. Since no report so far analyzed the literature documenting individual cases with electrolyte and acid-base derangements induced by trimethoprim, a systematic review was carried out.
EVIDENCE ACQUISITION
We retained 53 reports documenting 68 cases (42 males and 26 females 23 to 96 years of age) of electrolyte or acid-base derangements occurring on trimethoprim for about 5 days.
EVIDENCE SYNTHESIS
One hundred five electrolyte imbalances were detected in the 68 patients: hyperkalemia (>5.0 mmol/L) in 62 (91%), hyponatremia (<135 mmol/L) in 29 (43%) and metabolic acidosis (pH<7.38 and bicarbonate <19 mmol/L) in 14 (21%) cases. Following possible predisposing factors for electrolyte and acid-base abnormalities were found in 54 (79%) patients: high-dose trimethoprim, comedication with drugs that have been associated with electrolyte and acid-base derangements, preexisting kidney disease, age ≥80 years and diabetes mellitus.
CONCLUSIONS
High-dose trimethoprim, comedicated with drugs that have been associated with electrolyte and acid-base derangements, poor kidney function, age ≥80 years and diabetes mellitus predispose to trimethoprim-associated electrolyte and acid-base abnormalities. Clinicians must recognize patients at risk, possibly avoid drug combinations that may worsen the problem and monitor the laboratory values.
Topics: Acidosis; Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Bicarbonates; Diabetes Complications; Female; Humans; Hyperkalemia; Hyponatremia; Kidney Diseases; Male; Middle Aged; Trimethoprim; Young Adult
PubMed: 32697061
DOI: 10.23736/S0026-4806.20.06660-4 -
Cureus Dec 2022Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disease that lacks a definitive treatment. Lately, there has... (Review)
Review
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disease that lacks a definitive treatment. Lately, there has been an increased interest in the scientific community about the role of arginine in the short and long-term settings of the disease. We aim to conduct a systematic review of the clinical use of arginine in the management of MELAS and explore the role of arginine in the pathophysiology of the disease. We used PubMed advanced-strategy searches and only included full-text clinical trials on humans written in the English language. After applying the inclusion/exclusion criteria, four clinical trials were reviewed. We used the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for this systematic review. We used the Cochrane Collaboration risk-of-bias tool to assess the bias encountered in each study. Overall, IV arginine seems to be effective in improving symptoms during acute attacks of MELAS, while oral arginine supplementation increases endothelial function, preventing further stroke-like episodes.
PubMed: 36686069
DOI: 10.7759/cureus.32709 -
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 -
Clinical Journal of the American... Apr 2023Individuals with CKD are at a higher risk of cardiovascular morbidity and mortality. Acidosis is positively correlated with CKD progression and elevated systolic BP.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Individuals with CKD are at a higher risk of cardiovascular morbidity and mortality. Acidosis is positively correlated with CKD progression and elevated systolic BP. Sodium bicarbonate is an efficacious treatment of acidosis, although this may also increase systolic BP. In this systematic review and meta-analysis, we summarize the evidence evaluating systolic BP and antihypertensive medication change (which may indicate systolic BP change) in response to sodium bicarbonate therapy in individuals with CKD.
METHODS
Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) trials registry databases were searched for randomized control trials where sodium bicarbonate was compared with placebo/usual care in CKD stage G1-5 non-dialysis-dependent populations. Random effects meta-analyses were used to evaluate changes in systolic BP and BP-modifying drugs after sodium bicarbonate intervention.
RESULTS
Fourteen randomized control trials (2110 individuals, median follow-up 27 [interquartile range 97] weeks, mean age 60 [SD 10] years, mean systolic BP 136 [SD 17] mm Hg, mean eGFR 38 [SD 10] ml/min, mean serum bicarbonate 22 [SD 4] mmol/L) were eligible for inclusion. Meta-analysis suggested that sodium bicarbonate did not influence systolic BP in individuals with CKD stage G1-5. Results were consistent when stratifying by dose of sodium bicarbonate or duration of intervention. Similarly, there was no significant increase in the use of antihypertensive medication or diuretics in individuals taking sodium bicarbonate, whereas there was a greater decrease in antihypertensive medication use in individuals taking sodium bicarbonate compared with controls.
CONCLUSIONS
Our results suggest, with moderate certainty, that sodium bicarbonate supplementation does not adversely affect systolic BP in CKD or negatively influence antihypertensive medication requirements.
Topics: Humans; Middle Aged; Blood Pressure; Sodium Bicarbonate; Antihypertensive Agents; Kidney Failure, Chronic; Acidosis; Hypertension
PubMed: 36758154
DOI: 10.2215/CJN.0000000000000119 -
Open Access Emergency Medicine : OAEM 2023Heatstroke (HS) is a severe form of heat-related illness (HRI) associated with high morbidity and mortality, representing a condition that includes long-term multiorgan...
INTRODUCTION
Heatstroke (HS) is a severe form of heat-related illness (HRI) associated with high morbidity and mortality, representing a condition that includes long-term multiorgan dysfunction and susceptibility to further heat illness.
METHODS
In a systematic review searching Medline PubMed from the studies conducted between 2009 and 2020, 16 papers were identified.
RESULTS
A hallmark symptom of heat stroke is CNS dysfunction (a hallmark sign of HS) which manifests as mental status changes, including agitation, delirium, epilepsy, or coma at the time of the collapse. Acute kidney injury (AKI), gut ischemia, blood clots in the stomach and small intestine, cytoplasmic protein clumps in the spleen, and injury of skeletal muscle (rhabdomyolysis) are all characteristics of peripheral tissue damage. Severe heat stroke tends to be complicated by rhabdomyolysis, especially in patients with exertional heat stroke. Rhabdomyolysis may lead to systemic effects, including the local occurrence of compartment syndrome, hyperkalemic cardiac arrest, and/or lethal disseminated intravascular coagulopathy. Untreated heat stroke might exacerbate psychosis, lactic acidosis, consumptive coagulopathy, hematuria, pulmonary edema, renal failure, and other metabolic abnormalities. Core body temperature and level of consciousness are the most significant indicators to diagnose the severity of heat stroke and prevent unfavorable consequences. Heatstroke is a life-threatening illness if not promptly recognized and effectively treated.
DISCUSSION
This review highlighted that core body temperature and white blood cell count are significant contributing factors affecting heat stroke outcomes. Other factors contributing to the poor outcome include old age, low GCS, and prolonged hospital stay. The prevalence of both classic and exertional heatstroke can be reduced by certain simple preventive measures, such as avoiding strenuous activity in hot environments and reducing exposure to heat stress.
PubMed: 37771523
DOI: 10.2147/OAEM.S419028