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The Journal of Clinical Endocrinology... Jul 2022Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these... (Meta-Analysis)
Meta-Analysis
A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline for the Management of Hyperglycemia in Adults Hospitalized for Noncritical Illness or Undergoing Elective Surgical Procedures.
CONTEXT
Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging.
OBJECTIVE
To support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures.
METHODS
We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence.
RESULTS
We included 94 studies reporting on 135 553 patients. Compared with capillary blood glucose, continuous glucose monitoring increased the number of patients identified with hypoglycemia and decreased mean daily blood glucose (BG) (very low certainty). Data on continuation of insulin pump therapy in hospitalized adults were sparse. In hospitalized patients receiving glucocorticoids, combination neutral protamine hagedorn (NPH) and basal-bolus insulin was associated with lower mean BG compared to basal-bolus insulin alone (very low certainty). Data on NPH insulin vs basal-bolus insulin in hospitalized adults receiving enteral nutrition were inconclusive. Inpatient diabetes education was associated with lower HbA1c at 3 and 6 months after discharge (moderate certainty) and reduced hospital readmissions (very low certainty). Preoperative HbA1c level < 7% was associated with shorter length of stay, lower postoperative BG and a lower number of neurological complications and infections, but a higher number of reoperations (very low certainty). Treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors in hospitalized patients with type 2 diabetes and mild hyperglycemia was associated with lower frequency of hypoglycemic events than insulin therapy (low certainty). Caloric oral fluids before surgery in adults with diabetes undergoing surgical procedures did not affect outcomes (very low certainty). Counting carbohydrates for prandial insulin dosing did not affect outcomes (very low certainty). Compared with scheduled insulin (basal-bolus or basal insulin + correctional insulin), correctional insulin was associated with higher mean daily BG and fewer hypoglycemic events (low certainty).
CONCLUSION
The certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.
Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Elective Surgical Procedures; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin
PubMed: 35690929
DOI: 10.1210/clinem/dgac277 -
Scandinavian Journal of Surgery : SJS :... Jun 2021Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is...
BACKGROUND AND AIMS
Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is nowadays relatively more often diagnosed with intravenous contrast-enhanced computed tomography in the portal phase than at explorative laparotomy No high-quality comparative studies between anticoagulation alone, endovascular therapy, or surgery exists. The aim of the present systematic review was to offer a contemporary overview on management.
MATERIALS AND METHODS
Eleven relevant published original studies with series of at least ten patients were retrieved from a Pub Med search between 2015 and 2020 using the Medical Subject Heading term "mesenteric venous thrombosis."
RESULTS
When MVT is diagnosed early, immediate anticoagulation with either unfractionated heparin or subcutaneous low-molecular-weight heparin should commence. Surgeons need to be aware of the importance to scrutinize the computed tomography images themselves for assessment of secondary intestinal abnormalities to mesenteric venous thrombosis and the risk of bowel resection and worse prognosis. Progression toward peritonitis is an indication for explorative laparotomy and assessment of bowel viability. Frank transmural small bowel necrosis should be resected and bowel anastomosis may be delayed for several days until second look. Meanwhile, intravenous full-dose unfractionated heparin should be given at the end of the first operation. Postoperative major intra-abdominal or gastrointestinal bleeding occurs rarely, but the heparin effect can instantaneously be reversed by . Patients who do not improve during conservative therapy with anticoagulation alone but without developing peritonitis may be subjected to endovascular therapy in expert centers. When the patient's intestinal function has recovered, with or without bowel resection, switch from parenteral unfractionated heparin or low-molecular-weight heparin therapy to oral anticoagulation can be performed. There is a trend that direct oral anticoagulants are increasingly used instead of vitamin K antagonists. Up to now, direct oral anticoagulants have been shown to be equally effective with the same rate of bleeding complications. Patients with no strong permanent trigger factor for mesenteric venous thrombosis such as intra-abdominal cancer should undergo blood screening for inherited and acquired thrombophilia.
CONCLUSION
Early diagnosis with emergency computed tomography with intravenous contrast-enhancement and imaging in the portal phase and anticoagulation therapy is necessary to be able to have a succesful non-operative succesful course.
Topics: Anticoagulants; Heparin; Humans; Mesenteric Ischemia; Mesenteric Veins; Venous Thrombosis
PubMed: 33118463
DOI: 10.1177/1457496920969084 -
Reviews in Cardiovascular Medicine Jan 2022Perioperative anticoagulation management with uninterrupted or minimally interrupted anticoagulation during atrial fibrillation (AF) ablation is thought to be critical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perioperative anticoagulation management with uninterrupted or minimally interrupted anticoagulation during atrial fibrillation (AF) ablation is thought to be critical to minimize thromboembolic complications. Protamine is often administered to neutralize the effects of heparin and expedite vascular hemostasis post-procedure.
OBJECTIVE
We performed a systematic review and meta-analysis to determine the effectiveness of protamine to expedite vascular hemostasis and ambulation in patients undergoing AF ablation.
METHODS
Electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through August 7, 2021, were performed. The primary outcomes included-time to hemostasis (minutes) and time to ambulation (minutes). The secondary outcomes included - any vascular complications (excluding minor hematoma), minor hematoma, or cerebrovascular accidents (CVA).
RESULTS
A total of 5 eligible studies (3 retrospective cohort studies and two randomized trials) consisting of 1012 patients (515 patients received protamine group and 497 patients did not receive protamine group) were included in the meta-analysis. There was a significant reduction in time to ambulation [weighted mean difference (WMD) -176.6 minutes, 95% Confidence interval (CI) -266.9 to -86.3; < 0.01] and time to hemostasis (WMD -13.72 minutes, 95% CI -22 to -5.4, < 0.01) in the protamine group compared to the contrary. At a follow-up up to 3 months, there was no statistical difference between the two groups with regards to vascular complications (2.9% vs. 7.4%; Risk ratio (RR) 0.46 95% CI 0.17 to 1.24; = 0.12), minor hematoma (2.1% vs. 5.8%; RR 0.43, 95% CI 0.16 to 1.2; = 0.11) or CVA (0 vs. 0.3%; RR 0.62, 95% CI 0.08 to 4.98; = 0.65).
CONCLUSION
Protamine administration was associated with reduced time to ambulation (176 minutes reduction) and time to hemostasis (13 minutes reduction) without an increase in any adverse events.
Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Protamines; Retrospective Studies; Treatment Outcome
PubMed: 35092226
DOI: 10.31083/j.rcm2301034 -
Journal of Diabetes Jun 2023The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting... (Review)
Review
The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins (glargine U-300, degludec U-100, glargine U-100, detemir, and insulin protamine Hagedorn) in insulin-naïve adult patients with type 2 diabetes in the Asia-Pacific region. Based on evidence from a systematic review, we developed an Asia-Pacific clinical practice guideline through comprehensive internal review and external review processes. We set up and used clinical thresholds of trivial, small, moderate, and large effects for different critical and important outcomes in the overall certainty of evidence assessment and balancing the magnitude of intervention effects when making recommendations, following GRADE methods (Grading of Recommendations, Assessment, Development, and Evaluation). The AGREE (Appraisal of Guidelines, Research and Evaluation) and RIGHT (Reporting Items for practice Guidelines in HealThcare) guideline reporting checklists were complied with. After the second-round vote by the working group members, all the recommendations and qualifying statements reached over 75% agreement rates. Among 44 contacted external reviewers, we received 33 clinicians' and one patient's comments. The overall response rate was 77%. To solve the four research questions, we made two strong recommendations, six conditional recommendations, and two qualifying statements. Although the intended users of this guideline focused on clinicians in the Asia-Pacific region, the eligible evidence was based on recent English publications. We believe that the recommendations and the clinical thresholds set up in the guideline can be references for clinicians who take care of patients with type 2 diabetes worldwide.
Topics: Humans; Adult; Diabetes Mellitus, Type 2; Insulin Glargine; Insulin; Insulin, Long-Acting; Asia
PubMed: 37088916
DOI: 10.1111/1753-0407.13392 -
Diabetology & Metabolic Syndrome Oct 2022To assess the impact of long-acting insulin analogues, compared to intermediate acting neutral protamine Hagedron (NPH), on maternal, perinatal and neonatal outcomes. (Review)
Review
Maternal and neonatal outcomes with the use of long acting, compared to intermediate acting basal insulin (NPH) for managing diabetes during pregnancy: a systematic review and meta-analysis.
BACKGROUND
To assess the impact of long-acting insulin analogues, compared to intermediate acting neutral protamine Hagedron (NPH), on maternal, perinatal and neonatal outcomes.
METHODS
Studies for inclusion in the review were identified using a structured search strategy in PubMed, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) database. Studies that were randomized controlled trials or observational in design were considered for inclusion. Eligible studies should have compared the maternal, perinatal and neonatal outcomes between pregnant women with gestational diabetes mellitus (GDM) managed by intermediate acting (NPH) and by long-acting insulin analogues. Statistical analysis was performed using STATA software.
RESULTS
We found 17 studies to be eligible for inclusion. The mean gestational weight gain and risk of maternal hypoglycaemia, hypertensive disorder, caesarean delivery, spontaneous abortion, endometritis and wound infection or dehiscence were similar among pregnant women with GDM managed using long-acting insulin analogues and NPH. Those receiving long-acting insulin analogues had significantly lower HbA1c values in the second (WMD - .09, 95% CI 0.12, - 0.06; N = 4) and third trimester (WMD - 0.08, 95% CI - 0.14, - 0.02; N = 12). The mean gestational age and birth weight and risk of perinatal mortality, prematurity, large for gestational age, small for gestational age, shoulder dystocia and congenital abnormalities was similar among babies in both groups. No statistically significant differences in risk of admission to neonatal intensive care unit, respiratory distress, neonatal hypoglycaemia, 5 min APGAR score of < 7, neonatal hyperbilirubinemia and sepsis was observed. The quality of pooled evidence, as per GRADE criteria, was judged to be "very low" for all the maternal and neonatal outcomes considered.
CONCLUSIONS
Findings suggest no significant differences in the maternal, perinatal and neonatal outcomes between intermediate and long-acting insulin analogues. The results provide support for use of long-acting insulin analogues in women with GDM. However, evidence is still needed from high quality randomized controlled trials to arrive at a recommendation for inclusion in routine clinical care.
PubMed: 36271431
DOI: 10.1186/s13098-022-00925-7 -
Frontiers in Endocrinology 2024The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear... (Meta-Analysis)
Meta-Analysis
AIM
The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation.
METHODS
A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach.
RESULTS
Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses.
CONCLUSION
The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.
Topics: Humans; Insulin Glargine; Insulin, Long-Acting; Glycated Hemoglobin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Hypoglycemia; Insulin; Weight Gain; Protamines
PubMed: 38586456
DOI: 10.3389/fendo.2024.1286827 -
European Journal of Vascular and... Jan 2020Heparin has a non-predictable effect in the individual patient. The activated clotting time (ACT) is used to measure the level of anticoagulation after administration of...
OBJECTIVES
Heparin has a non-predictable effect in the individual patient. The activated clotting time (ACT) is used to measure the level of anticoagulation after administration of heparin. To date, appropriate heparin dose protocols and corresponding therapeutic ACT values have not been established in non-cardiac arterial procedures (NCAP). The aim of this review was to study the use of ACT monitoring during NCAP, and whether an optimal ACT could be determined based on the fewest arterial thrombo-embolic complications (ATEC) and bleeding complications.
METHODS
This systematic review was performed in accordance with the PRISMA Guidelines. A systematic search was conducted in MEDLINE, EMBASE, and the Cochrane database. Any associations were evaluated between peri-procedural ACT levels and ATEC and bleeding complications detected during the same admission as the primary procedure or during 30 day follow up. Also, heparin dose protocols, peri-procedural target ACTs, different ACT devices, protamine use and pre-, peri-, and post-procedural anticoagulation therapy were evaluated.
RESULTS
In total, 21 studies with 3982 patients were included, on both open and endovascular NCAP. Four studies were primarily designed to correlate peak peri-procedural ACT with clinical outcomes; however, the definitions of the results and the clinical outcomes were too heterogeneous for analysis. There was major variability in all studied aspects of ACT measurement, heparin and protamine use, and in the type of procedures in the included studies. Overall methodological quality of the included studies was poor. No randomised controlled trials were found. Studies were at a high risk of bias.
CONCLUSIONS
This systematic review demonstrates a lack of data and no consensus in the literature concerning the optimal ACT, and the possible association with haemorrhagic complications and ATEC during NCAP.
Topics: Anticoagulants; Arteries; Blood Coagulation; Blood Loss, Surgical; Consensus; Dose-Response Relationship, Drug; Drug Monitoring; Endovascular Procedures; Heparin; Humans; Monitoring, Intraoperative; Thromboembolism
PubMed: 31699657
DOI: 10.1016/j.ejvs.2019.08.007 -
Cureus Feb 2024The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the... (Review)
Review
BACKGROUND
The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes.
METHODS
We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding.
RESULTS
Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression.
CONCLUSIONS
There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.
PubMed: 38357407
DOI: 10.7759/cureus.54144 -
International Journal of Cardiology Oct 2023To determine the safety and efficacy of protamine in the reversal of heparin in percutaneous coronary intervention (PCI). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the safety and efficacy of protamine in the reversal of heparin in percutaneous coronary intervention (PCI).
BACKGROUND
Heparin is routinely used for anticoagulation in PCI. Protamine is not used routinely to reverse heparin's effects in PCI, partly due to the perceived risk of stent thrombosis.
METHODS
Relevant studies published in English were searched for in PubMed, Embase, and Cochrane databases from inception to April 26th, 2023. Our primary outcome of interest was stent thrombosis in patients receiving PCI for all indications. Secondary outcomes included mortality, major bleeding complications, and hospitalization length. Dichotomous outcomes were analyzed using a Mantel-Haenszel random-effects model and expressed as odds ratios (OR) with their 95% confidence intervals (CI), while continuous outcomes were analyzed using an inverse variance random-effects model expressed as mean differences (MD) with their 95% CI.
RESULTS
11 studies were included in our analysis. Protamine use was not associated with stent thrombosis: OR 0.58, 95% CI: 0.33, 1.01 (p = 0.05) nor with mortality (p = 0.89). Protamine administration was associated with a decreased incidence of major bleeding complications: OR 0.48; 95% CI: 0.25, 0.95 (p = 0.03) and decreased length of hospitalization (p < 0.0001).
CONCLUSIONS
In patients pre-treated with dual antiplatelet therapy (DAPT), protamine may be a safe and efficacious option to facilitate earlier sheath removal, reduce major bleeding complications, and reduce length of hospitalization without increased risk of stent thrombosis.
Topics: Humans; Heparin; Percutaneous Coronary Intervention; Protamines; Hemorrhage; Thrombosis; Platelet Aggregation Inhibitors; Treatment Outcome
PubMed: 37429445
DOI: 10.1016/j.ijcard.2023.131168 -
BMJ Open Nov 2022To examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and complications of long-acting and intermediate-acting insulin regimens for adults with type 1 diabetes: an individual patient data network meta-analysis.
OBJECTIVE
To examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus (T1DM).
DESIGN
Systematic review and individual patient data (IPD) network meta-analysis (NMA).
DATA SOURCES
MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through June 2015.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) on adults with T1DM assessing glycosylated haemoglobin (A1c) and severe hypoglycaemia in long-acting and intermediate-acting insulin regimens.
DATA EXTRACTION AND SYNTHESIS
We requested IPD from authors and funders. When IPD were not available, we used aggregate data. We conducted a random-effects model, and specifically a one-stage IPD-NMA for those studies providing IPD and a two-stage IPD-NMA to incorporate those studies not providing IPD.
RESULTS
We included 28 RCTs plus one companion report, after screening 6680 titles/abstracts and 205 full-text articles. Of the 28 RCTs, 27 studies provided data for the NMA with 7394 participants, of which 12 RCTs had IPD on 4943 participants. The IPD-NMA for A1c suggested that glargine once daily (mean difference [MD]=-0.31, 95% confidence interval [CI]: -0.48 to -0.14) and detemir once daily (MD=-0.25, 95% CI: -0.41 to -0.09) were superior to neutral protamine Hagedorn (NPH) once daily. NPH once/two times per day improved A1c compared with NPH once daily (MD=-0.30, 95% CI: -0.50 to -0.11). Results regarding complications in severe hypoglycaemia should be considered with great caution due to inconsistency in the evidence network. Accounting for missing data, there was no evidence of inconsistency and long-acting insulin regimens ranked higher regarding reducing severe hypoglycaemia compared with intermediate-acting insulin regimens (two-stage NMA: glargine two times per day SUCRA (Surface Under the Cumulative Ranking curve)=89%, detemir once daily SUCRA=77%; one-stage NMA: detemir once daily/two times per day SUCRA=85%). Using multiple imputations and IPD only, complications in severe hypoglycaemia increased with diabetes-related comorbidities (regression coefficient: 1.03, 95% CI: 1.02 to 1.03).
CONCLUSIONS
Long-acting insulin regimens reduced A1c compared with intermediate-acting insulin regimens and were associated with lower severe hypoglycaemia. Of the observed differences, only glargine once daily achieved a clinically significant reduction of 0.30%. Results should be interpreted with caution due to very low quality of evidence.
PROSPERO REGISTRATION NUMBER
CRD42015023511.
Topics: Adult; Humans; Diabetes Mellitus, Type 1; Insulin Glargine; Glycated Hemoglobin; Hypoglycemic Agents; Network Meta-Analysis; Insulin, Long-Acting; Insulin; Hypoglycemia; Insulin, Isophane
PubMed: 36332950
DOI: 10.1136/bmjopen-2021-058034