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Health Technology Assessment... Nov 2004To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness. (Review)
Review
OBJECTIVES
To evaluate the use of insulin glargine in its licensed basal-bolus indication in terms of both clinical and cost-effectiveness.
DATA SOURCES
Electronic databases.
REVIEW METHODS
A systematic review of the literature, involving a range of databases, was performed to identify all papers relating to insulin glargine.
RESULTS
Nineteen studies met the inclusion criteria but full reports were available for only six. For type 1 diabetes patients, insulin glargine appears to be more effective than neutral protamine Hagedorn (NPH) in reducing fasting blood glucose (FBG) but not in reducing glycosylated haemoglobin (HbA1c) and there is some evidence that both insulins are as effective as each other in both FBG and HbA1c control. For type 2 patients for whom oral antidiabetic agents provide inadequate glycaemic control, there is no evidence that insulin glargine is more effective than NPH in reducing either FBG or HbA1c and some evidence that both insulins are as effective as each other in both FBG and HbA1c control. Evidence for control of hypoglycaemia is equivocal. In studies where insulin glargine is demonstrated to be superior to NPH in controlling nocturnal hypoglycaemia, this may be only apparent when compared with once-daily NPH and not twice-daily NPH. Further, this superiority of glargine over NPH in the control of nocturnal hypoglycaemia may relate to one formulation of insulin glargine (HOE901[80]) and not another (HOE901[30]). There is no conclusive evidence that insulin glargine is superior to NPH in controlling symptomatic hypoglycaemia and severe hypoglycaemia. Insufficient data are available to conclude whether insulin glargine is different from each of the commonly used NPH dosing regimens: once daily and more than once daily. Given the lack of a published evidence base for the cost-effectiveness of insulin glargine, the economic review concentrates on a review of the industry submission and an amended model. Three economic models are provided in the submission, two relating to type 1 diabetes and one relating to type 2 diabetes. All three models compare the cost--utility of insulin glargine against NPH insulin. In general, the structures of the models are poor and in all three models, mistakes relating to assumptions and calculations have been made. The assessment team believe that the cost per QALY estimates generated by the Aventis model may be an underestimate for several reasons. The cost-effectiveness of insulin glargine in both type 1 and type 2 diabetes is highly sensitive to the amount of utility associated with reducing the fear of hypoglycaemia.
CONCLUSIONS
The evidence suggests that, compared with NPH insulin, insulin glargine is effective in reducing the number of nocturnal hypoglycaemic episodes, especially when compared with once-daily NPH. There appears to be no improvement in long-term glycaemic control and therefore insulin glargine is unlikely to reduce the incidence of the long-term microvascular and cardiovascular complications of diabetes. Further research into insulin glargine is needed that addresses the quality of life issues associated with fear of hypoglycaemia and also the economic impact of balance of HbA1c control and incidence of hypoglycaemia achieved in practice. Studies examining the economic evidence on insulin glargine should be published.
Topics: Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 15525480
DOI: 10.3310/hta8450 -
Cellular and Molecular Biology... Jul 2019Heparin and protamine are two indispensable agents of cardiopulmonary bypass surgery with effects on the cardiovascular and hematological system. Heparin is used as an...
Heparin and protamine are two indispensable agents of cardiopulmonary bypass surgery with effects on the cardiovascular and hematological system. Heparin is used as an anticoagulant in open heart surgery; whereas protamine is used to neutralize heparin effects when surgery is terminated. Protamine is given in order to neutralize heparin effects after cardiopulmonary bypass surgery and it causes hypotension in patients. However, the mechanism of this side effect is not clearly known. Current mechanism is that hypotension occurs after the administration of protamine due to the conformational change in the calcium channels or anaphylactoid thromboxane release or serum ionized calcium levels. The present study was to explain how protamine causes hypotension in evidence-based medicine indexed in PubMed and Web of Science. In addition to above mechanisms, possibly the infused protamine binds heparin and causes the coagulation cascade to activate heparin-AT complex on thrombin beside activating FXIa, FXa and FIXa and causing the re-use of Ca2+. The re-use of Ca2+ at the coagulation cascade initiates an anion gap and it is assumed that hypotension develops because of the Ca2+ deficiency. Ca2+ ions are trapped in the thrombus by the resumption of thrombus formation. Ca2+ ions trapped in the thrombus cannot be used, so that Ca2+ ion deficit will develop in circulation and hypotension occurs due to the insufficiency of Ca2+ ions. The administration of Ca2+ ions together with the protamine might help to eliminate the side effect of the protamine (hypotension) while neutralizing heparin after open heart surgery in light of the information provided in the literature.
Topics: Blood Pressure; Calcium; Cardiopulmonary Bypass; Homeostasis; Humans; Hypotension; Protamines; Thrombosis
PubMed: 31472056
DOI: No ID Found -
Scientific Reports Oct 2020Studies have reported the genetic gives rise to male infertility. The aim of the present meta-analysis was to evaluate the association between PRM1 (rs737008 and... (Meta-Analysis)
Meta-Analysis
Studies have reported the genetic gives rise to male infertility. The aim of the present meta-analysis was to evaluate the association between PRM1 (rs737008 and rs2301365) and PRM2 (rs1646022 and rs2070923) polymorphisms and susceptibility to male infertility. The association between PRM1 and PRM2 polymorphisms and the risk of male infertility was evaluated using specific search terms in the Web of Science, Cochrane Library, PubMed, and Scopus databases without language restriction until January 28, 2020. The association was determined by odds ratio (OR) and 95% confidence interval (CI) on five genetic models using Review Manager 5.3 software. The funnel plot analysis and sensitivity analysis were done by the Comprehensive Meta-analysis 2.0 software. Out of 261 records retrieved from the databases, 17 studies were analyzed in the meta-analysis, including the four PRM polymorphisms. The pooled results as OR (P-value) showed 0.96 (0.44), 1.04 (0.70), 0.94 (0.51), 0.94 (0.48), and 1.03 (0.72) for PRM1 rs737008 polymorphism and 1.67 (0.0007), 1.73 (0.06), 1.50 (0.007), 1.56 (0.004), and 1.62 (0.33) for PRM1 rs2301365 polymorphism in allele, homozygous, heterozygous, recessive, and dominant models, respectively. Moreover, the pooled results as OR (P-value) showed 1.19 (0.004), 1.15 (0.26), 1.08 (0.70), 1.05 (0.76), and 0.98 (0.82) for PRM2 rs1646022 and 0.88 (0.04), 0.84 (0.10), 1.05 (0.81), 0.90 (0.24), and 0.80 (0.02) for PRM2 rs2070923 in allele, homozygous, heterozygous, recessive, and dominant models, respectively. The results showed PRM1 rs2301365 and PRM2 rs1646022 polymorphisms were associated with an elevated risk of male infertility and PRM2 rs2070923 polymorphism had a protective role in infertile men.
Topics: Alleles; Genes, Dominant; Genes, Recessive; Genetic Association Studies; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Infertility, Male; Male; Polymorphism, Genetic; Protamines; Regression Analysis; Risk
PubMed: 33057064
DOI: 10.1038/s41598-020-74233-3 -
Basic & Clinical Pharmacology &... Aug 2008Anaphylactic reactions caused by injection of protamine sulfate during cardiac surgery are a well-known complication. A systematic literature review was therefore... (Review)
Review
Anaphylactic reactions caused by injection of protamine sulfate during cardiac surgery are a well-known complication. A systematic literature review was therefore conducted to gather evidence of the knowledge concerning these side effects, and to see if any prospective randomized studies supported this. Studies investigating the effect of protamine sulfate in human beings were extracted from MEDLINE, Embase and the Cochrane Library, retrieving 487 articles. Abstracts were evaluated by both authors, and referred articles not found in the primary search were furthermore extracted from reviews and case reports, resulting in a total of 272 relevant articles. Of these, 9 retrospective studies and 16 prospective studies were performed in an evidence-based manner. However, only 3 of the 16 prospective articles had an optimal design as far as inclusion criteria, randomization, and description of symptoms were concerned. Incidence of anaphylactic reactions in the prospective studies was 0.69% compared to 0.19% in the retrospective studies, but caution should be taken due to a pronounced heterogeneity of those studies. One study found heparinase I unsuitable as replacement for protamine sulfate. Overall, our findings support the low incidence of anaphylactic reactions reported in previous studies, but of note only few prospective investigations was conducted on the subject. Our study also emphasizes the need for critical appraisal of many routine procedures: in all aspects of medical care, systematic literature review conducted in a well-structured, repeated manner should be given high priority.
Topics: Anaphylaxis; Heparin Antagonists; Humans; Prospective Studies; Protamines; Randomized Controlled Trials as Topic
PubMed: 18816305
DOI: 10.1111/j.1742-7843.2008.00274.x -
Minerva Obstetrics and Gynecology Oct 2023The relative efficacy and safety of insulin neutral protamine Hagedorn (NPH) and detemir (IDet), in the management of diabetes in pregnancy remains unclear. We sought to...
INTRODUCTION
The relative efficacy and safety of insulin neutral protamine Hagedorn (NPH) and detemir (IDet), in the management of diabetes in pregnancy remains unclear. We sought to conduct an updated systematic review and meta-analysis to study the effect of NPH versus IDet during pregnancy on clinically relevant maternal and fetal outcomes.
EVIDENCE ACQUISITION
MEDLINE and Google Scholar were queried from inception till September 2022 for original studies comparing NPH with IDet for management of diabetes during pregnancy. Data was pooled using a random-effects model, to generate risk ratios (RR) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes, along with 95% confidence intervals (CIs). I test was used to assess the magnitude of heterogeneity. Sensitivity analysis was conducted to explore the potential source of heterogeneity. As less than ten studies were included in our analysis, funnel plots were not made to evaluate publication bias. A P value of ≤0.05 was considered significant in all cases.
EVIDENCE SYNTHESIS
Our search of the literature yielded 1087 articles initially, of which seven articles comprising 1396 patients, were included in our analysis. All included articles were of reasonably high methodological quality. Our pooled analysis demonstrates no statistically significant difference between the efficacy of insulin Detemir and insulin NPH as assessed by the HbA1c values from baseline. For safety outcomes, insulin detemir was significantly associated with a greater gestational age at delivery (WMD=0.39, 95%CI: 0.07 to 0.71, P=0.02) and lower incidence of hypoglycemic events (RR=0.64, 95%CI: 0.48 to 0.86, P=0.003) in-contrast to insulin NPH.
CONCLUSIONS
Our findings demonstrate that both, insulin IDet and insulin NPH have a similar efficacy in reducing HbA1c from baseline. However, insulin detemir was associated with lesser incidence of maternal hypoglycemic events and greater gestational age at delivery, compared to NPH.
PubMed: 37877940
DOI: 10.23736/S2724-606X.23.05318-6 -
Naunyn-Schmiedeberg's Archives of... Oct 2021We aimed to assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and... (Meta-Analysis)
Meta-Analysis
We aimed to assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults.PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with ≥ 12 weeks of follow-up comparing efficacy (HbA) or safety (hypoglycemia and weight gain) between second-generation basal insulins vs. other basal insulins in T1D adults were included. Bayesian network meta-analyses were used to estimate risk ratio, hazard ratio, and mean difference. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to appraise evidence certainty.Eighteen RCTs (≥ 24 weeks of follow-up) involving 7283 randomized participants were included for main analysis. Moderate to high certainty evidence suggested that second-generation basal insulins showed equivalent HbA reduction compared with NPH and first-generation basal insulins. Compared with second-generation basal insulins, low to high certainty evidence suggested that NPH was associated with a higher risk of patients experiencing severe hypoglycemia; NPH and first-generation basal insulins were associated with a higher rate of nocturnal confirmed hypoglycemic events. For the weight gain, glargine U300 was comparable to detemir (low certainty), but degludec U100 was greater than detemir (moderate certainty).In conclusion, second-generation basal insulins maintained equivalent efficacy of glycemic control (moderate to high certainty), with differences in safety (low to high certainty) compared with NPH and first-generation basal insulins during ≥ 24 weeks of follow-up in T1D adults.
Topics: Adult; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain
PubMed: 34319421
DOI: 10.1007/s00210-021-02128-9 -
Endocrine Practice : Official Journal... Feb 2018Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes... (Review)
Review
OBJECTIVE
Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes management during air travel to summarize current recommendations, assess supporting evidence, and identify areas of future research.
METHODS
A systematic review of the English literature on diabetes management during air travel was undertaken utilizing PubMed and MEDLINE. Publications regarding general travel advice; adjustment of insulin and noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous glucose sensors at altitude were included. Gathered information was used to create an updated summary of glucose-lowering medication adjustment during air travel.
RESULTS
Sixty-one publications were identified, most providing expert opinion and few offering primary data (47 expert opinion, 2 observational studies, 2 case reports, 10 device studies). General travel advice was uniform, with increasing attention to preflight security. Indications for oral antihyperglycemic therapy adjustments varied. There were few recommendations on contemporary agents and on nonhypoglycemic adverse events. There was little consensus on insulin adjustment protocols, many antedating current insulin formulations. Most publications advocated adjusting insulin pump time settings after arrival; however, there was disagreement on timing and rate adjustments. Glucometers and subcutaneous glucose sensors were reported to be less accurate at altitude, but not to an extent that would preclude their clinical use.
CONCLUSION
Recommendations for diabetes management during air travel vary significantly and are mostly based on expert opinion. Data from systematic investigation on glucose-lowering medication adjustment protocols may support the development of a future consensus statement.
ABBREVIATIONS
CSII = continuous subcutaneous insulin infusion (device) DPP-4 = dipeptidyl peptidase 4 EGA = error grid analysis GDH = glucose dehydrogenase GOX = glucose oxidase GLP1 = glucagon-like peptide-1 NPH = neutral protamine Hagedorn SGLT2 = sodium-glucose cotransporter-2.
Topics: Air Travel; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Evidence-Based Practice; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Practice Guidelines as Topic
PubMed: 29466062
DOI: 10.4158/EP171954.RA -
International Journal of Clinical... Mar 2014It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar).
METHODS
The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
Five trials, including a total number of 1758 patients followed up from 24 to 28 weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3 RCTs; WMD (95% CI): -14.70 mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09 mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR = 1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI) = 0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI) = 1.78 kg (1.04; 2.52)].
CONCLUSIONS
BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk of severe hypoglycaemic episodes.
Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain
PubMed: 24471814
DOI: 10.1111/ijcp.12337 -
Medicine Dec 2019Hemocoagulase is isolated and purified from snake venoms. Hemocoagulase agents have been widely used in the prevention and treatment of surgical bleeding. A systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemocoagulase is isolated and purified from snake venoms. Hemocoagulase agents have been widely used in the prevention and treatment of surgical bleeding. A systematic review was performed to evaluate the effects of hemocoagulase on postoperative bleeding and transfusion in patients who underwent cardiac surgery.
METHODS
Electronic databases were searched to identify all clinical trials comparing hemocoagulase with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Two authors independently extracted perioperative data and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. Sensitivity analyses were done by examining the influence of statistical model and individual trial on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P < .05.
RESULTS
Our search yielded 12 studies including 900 patients, and 510 patients were allocated into hemocoagulase group and 390 into control group. Meta-analysis suggested that, hemocoagulase-treated patients had less bleeding volume, reduced red blood cells and fresh frozen plasma transfusion, and higher hemoglobin level than those of controlled patients postoperatively. Meta-analysis also showed that, hemocoagulase did not influence intraoperative heparin or protamine dosages and postoperative platelet counts. Meta-analysis demonstrated that, hemocoagulase-treated patients had significantly shorter postoperative prothrombin time, activated partial thromboplastin time, and thrombin time, higher fibrinogen level and similar D-dimer level when compared to control patients.
CONCLUSION
This meta-analysis has found some evidence showing that hemocoagulase reduces postoperative bleeding, and blood transfusion requirement in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Hemocoagulase.
Topics: Batroxobin; Blood Transfusion; Cardiac Surgical Procedures; Hemostatics; Humans; Postoperative Hemorrhage
PubMed: 31876750
DOI: 10.1097/MD.0000000000018534 -
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