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Journal of the American Pharmacists... 2024The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported.
OBJECTIVE
This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents.
METHODS
A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software.
RESULTS
Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables.
CONCLUSIONS
Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance.
Topics: Adult; Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Ketoacidosis; Prevalence; Sodium-Glucose Transporter 2; Nimustine; Diabetes Mellitus, Type 2; Hypoglycemic Agents
PubMed: 37844733
DOI: 10.1016/j.japh.2023.10.010 -
Actas Urologicas Espanolas Feb 2024Patients undergoing radical cystectomy with urinary diversions (UD) are at increased risk of bone fractures compared to the general population. Although a loss of bone... (Review)
Review
Why do patients with urinary diversions have an increased risk of bone fracture? A systematic review on risk factors for osteoporosis and bone mineral density loss in this group of patients.
INTRODUCTION
Patients undergoing radical cystectomy with urinary diversions (UD) are at increased risk of bone fractures compared to the general population. Although a loss of bone mineral density (BMD) has been described in patients with UD, we still do not know with certainty why these patients follow this tendency.
OBJECTIVE
We performed a systematic review of the available literature to analyze the prevalence of osteoporosis and bone alterations in patients with ileal UD and the possible associated risk factors.
EVIDENCE ACQUISITION
We systematically searched PubMed® and Cochrane Library for original articles published before December 2022 according to PRISMA guidelines.
EVIDENCE SYNTHESIS
A total of 394 publications were identified. We selected 12 studies that met the inclusion criteria with 496 patients included. Six of the twelve studies showed decreased BMD values. Prevalence of osteoporosis was specified in three articles, with values ranging from 0% to 36%. Risk factors such as age, sex, body mass index, metabolic acidosis and renal function appear to have an impact on bone tissue reduction, while type of UD, follow-up, 25-hydroxyvitamin D and parathormone had less evidence or contradictory data. The heterogeneity of the studies analyzed could led to interpretation bias.
CONCLUSIONS
UD are associated with multiple risk factors for osteoporosis and bone fractures. Identifying patients at highest risk and establishing diagnostic protocols in routine clinical practice are essential to reduce the risk of fractures and the resulting complications.
PubMed: 38365091
DOI: 10.1016/j.acuroe.2023.11.009 -
Polymers Mar 2024Poly-L-lactic acid (PLLA) implants have been used for bone fixation for decades. However, upon insertion, they can cause a foreign body reaction (FBR) that may lead to... (Review)
Review
Poly-L-lactic acid (PLLA) implants have been used for bone fixation for decades. However, upon insertion, they can cause a foreign body reaction (FBR) that may lead to complications. On 15 December 2023, a systematic review was conducted to search for articles on the PubMed, MeSH term, and Scopus databases using the keywords 'PLLA' and 'foreign body reaction'. The articles were reviewed not only for the question of FBR, its severity, and the manifestation of symptoms but also for the type of implant and its location in the body, the species, and the number of individuals included. A total of 71 original articles were identified. Of these, two-thirds reported on in vivo trials, and one-third reported on clinical applications. The overall majority of the reactions were mild in more than half of the investigations. Symptoms of extreme and extensive FBR mainly include osteolysis, ganglion cysts, and swelling. The localization of PLLA implants in bone can often result in osteolysis due to local acidosis. This issue can be mitigated by adding hydroxyapatite. There should be no strong FBR when PLLA is fragmented to 0.5-4 µm by extracorporeal shock wave.
PubMed: 38543422
DOI: 10.3390/polym16060817 -
Acta Obstetricia Et Gynecologica... Mar 2024ST waveform analysis (STAN) was introduced as an adjunct to cardiotocography (CTG) to improve neonatal and maternal outcomes. The aim of the present study was to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
ST waveform analysis (STAN) was introduced as an adjunct to cardiotocography (CTG) to improve neonatal and maternal outcomes. The aim of the present study was to quantify the efficacy of STAN vs CTG and assess the quality of the evidence using GRADE.
MATERIAL AND METHODS
We performed systematic literature searches to identify randomized controlled trials and assessed included studies for risk of bias. We performed meta-analyses, calculating pooled risk ratio (RR) or Peto odds ratio (OR). We also performed post hoc trial sequential analyses for selected outcomes to assess the risk of false-positive results and the need for additional studies.
RESULTS
Nine randomized controlled trials including 28 729 women were included in the meta-analysis. There were no differences between the groups in operative deliveries for fetal distress (10.9 vs 11.1%; RR 0.96; 95% confidence interval [CI] 0.82-1.11). STAN was associated with a significantly lower rate of metabolic acidosis (0.45% vs 0.68%; Peto OR 0.66; 95% CI 0.48-0.90). Accordingly, 441 women need to be monitored with STAN instead of CTG alone to prevent one case of metabolic acidosis. Women allocated to STAN had a reduced risk of fetal blood sampling compared with women allocated to conventional CTG monitoring (12.5% vs 19.6%; RR 0.62; 95% CI 0.49-0.80). The quality of the evidence was high to moderate.
CONCLUSIONS
Absolute effects of STAN were minor and the clinical significance of the observed reduction in metabolic acidosis is questioned. There is insufficient evidence to state that STAN as an adjunct to CTG leads to important clinical benefits compared with CTG alone.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Cardiotocography; Randomized Controlled Trials as Topic; Fetal Distress; Electrocardiography; Acidosis; Fetal Monitoring; Heart Rate, Fetal
PubMed: 38093630
DOI: 10.1111/aogs.14752 -
Enfermedades Infecciosas Y... 2024The occurrence of mucormycosis has been observed in individuals with COVID-19. However, there is limited information on the epidemiological factors, presentation,... (Review)
Review
The occurrence of mucormycosis has been observed in individuals with COVID-19. However, there is limited information on the epidemiological factors, presentation, diagnostic certainty, and outcome of this infection in children. PubMed, MEDLINE, Scopus, Embase, Web of Science, LitCovid, and back-references of the identified manuscripts were systematically searched from December 2019 to March 2023. We have identified 14 cases of pediatric mucormycosis in patients with COVID-19. The median age of patients was 10.7 years. Among these cases, 10 were associated with active COVID-19. In 7 cases, the patients had pre-existing diabetes mellitus and concomitant diabetic ketoacidosis. Corticosteroids were administered to treat COVID-19 in 7 of the patients. The most common clinical presentation of the disease was rhino-orbital cerebral mucormycosis. Seven patients died (50%). Given the high mortality rate, clinicians should maintain a high level of clinical suspicion of mucormycosis in pediatric patients with COVID-19.
Topics: Humans; Mucormycosis; COVID-19; Child; Adolescent; Child, Preschool; Female; Male; Diabetic Ketoacidosis
PubMed: 38216422
DOI: 10.1016/j.eimce.2023.11.006 -
World Journal of Clinical Cases Aug 2023Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below...
BACKGROUND
Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below 200 mg/dL. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can induce eu-DKA in diabetic patients. Notably, coronavirus disease 2019 (COVID-19) -infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets. This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis. Additionally, we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors, providing indispensable insights for healthcare professionals managing this specific patient population.
AIM
To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.
METHODS
We conducted an exhaustive search across prominent electronic databases, including PubMed, SCOPUS, Web of Science, and Google Scholar. This search encompassed the period from December 2019 to May 2022, incorporating published studies and pre-prints. The search terms employed encompassed "SGLT2 inhibitors", "euglycemic DKA", "COVID-19", and related variations. By incorporating these diverse sources, our objective was to ensure a thorough exploration of the existing literature on this subject, thereby augmenting the validity and robustness of our findings.
RESULTS
Our search yielded a total of seven case reports and one case series, collectively comprising a cohort of twelve patients. These reports detailed instances of eu-DKA in individuals with COVID-19. Crucially, all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication. Upon admission, all oral medications were promptly discontinued, and the patients were initiated on intravenous insulin therapy to effectively manage the DKA. Encouragingly, eleven patients demonstrated a favorable outcome, while regrettably, one patient succumbed to the condition. Subsequently, SGLT2 were discontinued for all patients upon their discharge from the hospital. These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2, underscoring the critical importance of prompt intervention and vigilant medication adjustments.
CONCLUSION
Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA, as well as encountering adverse outcomes in the context of COVID-19, despite maintaining satisfactory glycemic control. The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous. Consequently, this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.
PubMed: 37727728
DOI: 10.12998/wjcc.v11.i24.5700 -
The Cochrane Database of Systematic... May 2024Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with diabetes are more likely to develop kidney impairment, and approximately one in three adults with diabetes have CKD. People with CKD and diabetes experience a substantially higher risk of cardiovascular outcomes. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have shown potential effects in preventing kidney and cardiovascular outcomes in people with CKD and diabetes. However, new trials are emerging rapidly, and evidence synthesis is essential to summarising cumulative evidence.
OBJECTIVES
This review aimed to assess the benefits and harms of SGLT2 inhibitors for people with CKD and diabetes.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2023 using a search strategy designed by an Information Specialist. Studies in the Register are continually identified through regular searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled studies were eligible if they evaluated SGLT2 inhibitors versus placebo, standard care or other glucose-lowering agents in people with CKD and diabetes. CKD includes all stages (from 1 to 5), including dialysis patients.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the study risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary review outcomes were all-cause death, 3-point and 4-point major adverse cardiovascular events (MACE), fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and kidney failure.
MAIN RESULTS
Fifty-three studies randomising 65,241 people with CKD and diabetes were included. SGLT2 inhibitors with or without other background treatments were compared to placebo, standard care, sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin. In the majority of domains, the risks of bias in the included studies were low or unclear. No studies evaluated the treatment in children or in people treated with dialysis. No studies compared SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists or tirzepatide. Compared to placebo, SGLT2 inhibitors decreased the risk of all-cause death (20 studies, 44,397 participants: RR 0.85, 95% CI 0.78 to 0.94; I = 0%; high certainty) and cardiovascular death (16 studies, 43,792 participants: RR 0.83, 95% CI 0.74 to 0.93; I = 29%; high certainty). Compared to placebo, SGLT2 inhibitors probably make little or no difference to the risk of fatal or nonfatal MI (2 studies, 13,726 participants: RR 0.95, 95% CI 0.80 to 1.14; I = 24%; moderate certainty), and fatal or nonfatal stroke (2 studies, 13,726 participants: RR 1.07, 95% CI 0.88 to 1.30; I = 0%; moderate certainty). Compared to placebo, SGLT2 inhibitors probably decrease 3-point MACE (7 studies, 38,320 participants: RR 0.89, 95% CI 0.81 to 0.98; I = 46%; moderate certainty), and 4-point MACE (4 studies, 23,539 participants: RR 0.82, 95% CI 0.70 to 0.96; I = 77%; moderate certainty), and decrease hospital admission due to heart failure (6 studies, 28,339 participants: RR 0.70, 95% CI 0.62 to 0.79; I = 17%; high certainty). Compared to placebo, SGLT2 inhibitors may decrease creatinine clearance (1 study, 132 participants: MD -2.63 mL/min, 95% CI -5.19 to -0.07; low certainty) and probably decrease the doubling of serum creatinine (2 studies, 12,647 participants: RR 0.70, 95% CI 0.56 to 0.89; I = 53%; moderate certainty). SGLT2 inhibitors decrease the risk of kidney failure (6 studies, 11,232 participants: RR 0.70, 95% CI 0.62 to 0.79; I = 0%; high certainty), and kidney composite outcomes (generally reported as kidney failure, kidney death with or without ≥ 40% decrease in estimated glomerular filtration rate (eGFR)) (7 studies, 36,380 participants: RR 0.68, 95% CI 0.59 to 0.78; I = 25%; high certainty) compared to placebo. Compared to placebo, SGLT2 inhibitors incur less hypoglycaemia (16 studies, 28,322 participants: RR 0.93, 95% CI 0.89 to 0.98; I = 0%; high certainty), and hypoglycaemia requiring third-party assistance (14 studies, 26,478 participants: RR 0.75, 95% CI 0.65 to 0.88; I = 0%; high certainty), and probably decrease the withdrawal from treatment due to adverse events (15 studies, 16,622 participants: RR 0.94, 95% CI 0.82 to 1.08; I = 16%; moderate certainty). The effects of SGLT2 inhibitors on eGFR, amputation and fracture were uncertain. No studies evaluated the effects of treatment on fatigue, life participation, or lactic acidosis. The effects of SGLT2 inhibitors compared to standard care alone, sulfonylurea, DPP-4 inhibitors, or insulin were uncertain.
AUTHORS' CONCLUSIONS
SGLT2 inhibitors alone or added to standard care decrease all-cause death, cardiovascular death, and kidney failure and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Bias; Cause of Death; Hypoglycemic Agents; Benzhydryl Compounds; Glucosides
PubMed: 38770818
DOI: 10.1002/14651858.CD015588.pub2 -
BMJ Open Feb 2024This systematic review and meta-analysis aimed to assess the magnitude and determinants of diabetic ketoacidosis (DKA) among patients with diabetes mellitus (DM) in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis aimed to assess the magnitude and determinants of diabetic ketoacidosis (DKA) among patients with diabetes mellitus (DM) in Ethiopia.
DESIGN
Systematic review and meta-analysis.
PARTICIPANTS
Age 15 and above all patients with diabetes with the diagnosis of DKA in Ethiopia DATA SOURCE: PubMed/MEDLINE, Cochrane Library, Science Direct, HINARI, Google Scholar and grey literatures were accessed to find relevant articles. Studies that have been conducted and reported in English language, articles with an available full-text, and observational studies were included. The task of searching sources was carried out from all stated electronic databases performed during 15 April-29 April 2023.
PRIMARY AND SECONDARY OUTCOME MEASURES
Eligible studies were critically appraised by three independent reviewers for methodological quality in the review using standardised critical appraisal instruments from Joanna Briggs Institute (JBI) for observational studies. After the finally extracted studies were exported, systematic review and meta-analysis were conducted using Unified Management, Assessment and Review of Information (JBI SUMARI) (JBI, Adelaide, Australia) and STATA V.17 software. Sensitivity tests were done, and funnel plot inspections with Egger's test were used to check for publication bias.
RESULT
From a total of 19 studies with 6498 study participants, the pooled prevalence of DKA among patients with DM in Ethiopia was 30.92% (95% CI 29.96 to 31.89) with a significant statistical heterogeneity (I=99.2, p=<0.001). Sensitivity analysis suggested that three studies showed deviations from the estimated pooled prevalence. A funnel plot inspection and Egger's test indicated the absence of a publication bias.
CONCLUSION
This systematic review and meta-analysis revealed that the prevalence of DKA among patients with DM in Ethiopia was 30.92%. Besides, different behavioural and clinical determinants of DKA among patients with DM were identified. However, further studies should be conducted, particularly on the possible determinants of DKA, and different stakeholders should be engaged to minimise its burden.
Topics: Humans; Adolescent; Diabetic Ketoacidosis; Ethiopia; Prevalence; Databases, Factual; Australia; Diabetes Mellitus
PubMed: 38341216
DOI: 10.1136/bmjopen-2023-077151 -
Nutrition, Metabolism, and... Mar 2024Chronic metabolic acidosis has been shown to be associated with cardiometabolic risk factors. The aim of the currently updated meta-analysis was to explore the... (Meta-Analysis)
Meta-Analysis
AIMS
Chronic metabolic acidosis has been shown to be associated with cardiometabolic risk factors. The aim of the currently updated meta-analysis was to explore the association between Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) with these risk factors.
DATA SYNTHESIS
Databases were searched up to May 2023. The mean of waist circumference (WC), body mass index (BMI), high- and low-density lipoprotein-cholesterol (HDL-C and LDL-C), triglyceride (TG), total cholesterol (TC), fasting blood sugar (FBS), and systolic- and diastolic blood pressure (SBP and DBP) in highest category vs lowest categories of NEAP and PRAL were recorded. Effect sizes were generated as weighted mean difference (WMD). Results showed that SBP, DBP, and WC had a significant difference in the upper and lower categories of PRAL (WMD: 1.466 mmHg; 95% CI: 2.121, -0.811; P<0.001, WMD: 0.710 mmHg; 95 % CI: 1.170, -0.249; P=0.003, and WMD: 0.819 cm; 95% CI: 1.446, -0.192; P=0.010) or NEAP (WMD: 1.690 mmHg; 95% CI: 2.789, -0.591; P=0.003, WMD: 1.076 mmHg, and WMD: 1.325 cm; 95% CI: 1.901, -0.749; P<0.001; 95% CI: 1.938, -0.214; P =0.014). The lowest versus highest categories of dietary PRAL were associated with lower BMI (WMD: 0.297 kg/m2; 95 % CI: 0.440, -0.154; P<0.001) and TG (WMD: 2.280 mg/dl; 95%CI: 3.828, -0.732; P=0.004; I=99.4 %; P<0.001).
CONCLUSIONS
High DAL can be considered as an independent risk factor for increasing anthropometric indices, blood pressure, and TG. This study registered in the PROSPERO database (Registration No. CRD42023402985).
Topics: Humans; Diet; Risk Factors; Anthropometry; Cholesterol, HDL; Cardiovascular Diseases
PubMed: 38316575
DOI: 10.1016/j.numecd.2024.01.013 -
Journal of Evidence-based Medicine Jun 2024To determine the comparative effectiveness of fluid schemes for children with diabetic ketoacidosis (DKA).
AIM
To determine the comparative effectiveness of fluid schemes for children with diabetic ketoacidosis (DKA).
METHODS
We conducted a systematic review with an attempt to conduct network meta-analysis (NMA). We searched MEDLINE, EMBASE, CENTRAL, Epistemonikos, Virtual Health Library, and gray literature from inception to July 31, 2022. We included randomized controlled trials (RCTs) in children with DKA evaluating any intravenous fluid schemes. We planned to conduct NMA to compare all fluid schemes if heterogeneity was deemed acceptable.
RESULTS
Twelve RCTs were included. Studies were heterogeneous in the population (patients and DKA episodes), interventions with different fluids (saline, Ringer's lactate (RL), and polyelectrolyte solution-PlasmaLyte), tonicity, volume, and administration systems. We identified 47 outcomes that measured clinical manifestations and metabolic control, including single and composite outcomes and substantial heterogeneity preventing statistical combination. No evidence was found of differences in neurological deterioration (main outcome), but differences were found among interventions in some comparisons to normalize acid-base status (∼2 h less with low vs. high volume); time to receive subcutaneous insulin (∼1 h less with low vs. high fluid rate); length of stay (∼6 h less with RL vs. saline); and resolution of the DKA (∼3 h less with two-bag vs. one-bag scheme). However, available evidence is scarce and poor.
CONCLUSIONS
There is not enough evidence to determine the best fluid therapy in terms of fluid type, tonicity, volume, or administration time for DKA treatment. There is an urgent need for more RCTs, and the development of a core outcome set on DKA in children.
Topics: Humans; Diabetic Ketoacidosis; Fluid Therapy; Child; Randomized Controlled Trials as Topic
PubMed: 38572835
DOI: 10.1111/jebm.12603