-
Journal of Stroke and Cerebrovascular... Oct 2019Administering intravenous IV tissue plasminogen activator (tPA) is the recommended standard of care in acute ischemic stroke (AIS), although it is not recommended to...
INTRODUCTION
Administering intravenous IV tissue plasminogen activator (tPA) is the recommended standard of care in acute ischemic stroke (AIS), although it is not recommended to administer intravenous thrombolysis with tPA following heparin reversal with protamine sulfate in patients with AIS.
METHODS
We describe a case series of three patients and the most comprehensive literature review published to date in this specific subset of AIS patients undergoing thrombolysis following heparin reversal with protamine sulfate. The literature review was based on a scoping review methodology performed on four databases; PubMed, CINAHL, Web of Science, and Cochrane Library. All sources were searched from the inauguration of the database until February 2019. A total of six articles involving eight patients were identified.
RESULTS
The primary safety outcome of no symptomatic intracranial hemorrhage (sICH) was met in all eleven patients, although only seven cases had a good functional outcome at 3 months.
CONCLUSIONS
In appropriately selected AIS patients, coagulopathy correction appears to be safe from an sICH standpoint and may be beneficial. However, given the potential for bias with observational databases, case reports and case series, extreme caution is warranted in applying these results to routine clinical practice.
Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Brain Ischemia; Female; Fibrinolytic Agents; Heparin; Heparin Antagonists; Humans; Male; Middle Aged; Protamines; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 31324409
DOI: 10.1016/j.jstrokecerebrovasdis.2019.06.041 -
BMJ Open Jun 2019What is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on...
OBJECTIVES
What is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy?
DESIGN
We conducted a systematic literature review.
DATA SOURCES
We searched MEDLINE, Embase and Cochrane Library databases and Google for articles from 2002 to July 2018.
ELIGIBILITY CRITERIA
We combined search terms relating to DM (patients, >16 years of age), systemic glucocorticoids, glycaemic control, randomised controlled trials (RCTs) and observational studies.
DATA EXTRACTION AND SYNTHESIS
We screened and evaluated articles, extracted data and assessed risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development and Evaluation guidelines.
RESULTS
Eight of 2365 articles met full eligibility criteria. Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective but provided insufficient glucose control, depending on time of day. BBI strategy with long-acting insulin and neutral protamin Hagedorn as basal insulin provided similar overall glycaemic control. Addition of various insulin strategies to standard BBI delivered mixed results. Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits, and glycaemic control with sliding scale insulin was inferior to BBI or IMI. No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control.
CONCLUSION
The lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of DM subgroups and low to moderate quality of evidence render identification of optimal pharmacological interventions for glycaemic control and insulin management difficult. Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive. High-quality evidence from studies with well-defined DM phenotypes, settings and treatment approaches is needed to determine optimal pharmacological intervention for glycaemic control.
PROSPERO REGISTRATION NUMBER
CRD42015024739.
Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucocorticoids; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 31154314
DOI: 10.1136/bmjopen-2019-028914 -
The American Journal of Managed Care Jul 2018The objective of this literature review was to evaluate the costs associated with the use of long-acting insulin analogues (LAIAs) compared with non-LAIA agents,... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
The objective of this literature review was to evaluate the costs associated with the use of long-acting insulin analogues (LAIAs) compared with non-LAIA agents, including human insulin, oral antidiabetic drugs, and other injectable therapies, in the treatment of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).
STUDY DESIGN
A systematic review of the medical literature (MEDLINE, EMBASE, Cochrane, EconLit) conducted from 2004 to 2016.
METHODS
The review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria for studies were: patients with T1D and/or T2D, LAIA intervention, and comparators, including oral antidiabetics (OADs) or neutral protamine Hagedorn (NPH). Outcomes of interest were adherence measures; economic outcomes, including total costs, cost savings, and willingness-to-pay; and cost-effectiveness or incremental cost-effectiveness analyses. Real-world costs of individual LAIAs were also evaluated and are often compared against those of other LAIAs in the economic analyses.
RESULTS
We identified and included 117 relevant studies. Patients using LAIAs had higher drug costs than those using OADs and NPH but had neutral or reduced total and diabetes-related costs compared with patients using non-LAIAs. Use of LAIA pen-delivery systems may lead to improved adherence and reduction in costs. Patients receiving insulin glargine demonstrated higher adherence and persistence than patients on insulin detemir. Economic models suggest that LAIAs are more cost-effective than NPH for T1D; for T2D, insulin glargine is more costly than NPH but less so than insulin detemir.
CONCLUSIONS
Despite higher drug costs, the real-world overall medical costs of LAIAs are not significantly different from those of NPH in patients with diabetes. The findings may be helpful for formulary decision making for patients with diabetes in a cost-constrained environment.
Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Costs; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Quality-Adjusted Life Years; United States
PubMed: 30020738
DOI: No ID Found -
Basic and Clinical Andrology 2018The nuclear lamina (NL) is a filamentous protein meshwork, composed essentially of lamins, situated between the inner nuclear membrane and the chromatin. The NL is a...
The nuclear lamina (NL) is a filamentous protein meshwork, composed essentially of lamins, situated between the inner nuclear membrane and the chromatin. The NL is a component of the nuclear envelope, interacts with a wide range of proteins and is required for normal nuclear structure and physiological development. During spermiogenesis the spermatid nucleus is elongated, and dramatically reduced in size with protamines replacing histones to produce a highly compacted chromatin. There is mounting evidence from studies in human and rodent, that the NL plays an important role in mammalian spermatid differentiation during spermiogenesis. In this review, we summarize and discuss the data available in the literature regarding the involvement of lamins and their direct or indirect partners in normal and abnormal human spermiogenesis.
PubMed: 29946470
DOI: 10.1186/s12610-018-0072-4 -
Journal of Medical Internet Research May 2018Adverse events in health care entail substantial burdens to health care systems, institutions, and patients. Retrospective trigger tools are often manually applied to...
BACKGROUND
Adverse events in health care entail substantial burdens to health care systems, institutions, and patients. Retrospective trigger tools are often manually applied to detect AEs, although automated approaches using electronic health records may offer real-time adverse event detection, allowing timely corrective interventions.
OBJECTIVE
The aim of this systematic review was to describe current study methods and challenges regarding the use of automatic trigger tool-based adverse event detection methods in electronic health records. In addition, we aimed to appraise the applied studies' designs and to synthesize estimates of adverse event prevalence and diagnostic test accuracy of automatic detection methods using manual trigger tool as a reference standard.
METHODS
PubMed, EMBASE, CINAHL, and the Cochrane Library were queried. We included observational studies, applying trigger tools in acute care settings, and excluded studies using nonhospital and outpatient settings. Eligible articles were divided into diagnostic test accuracy studies and prevalence studies. We derived the study prevalence and estimates for the positive predictive value. We assessed bias risks and applicability concerns using Quality Assessment tool for Diagnostic Accuracy Studies-2 (QUADAS-2) for diagnostic test accuracy studies and an in-house developed tool for prevalence studies.
RESULTS
A total of 11 studies met all criteria: 2 concerned diagnostic test accuracy and 9 prevalence. We judged several studies to be at high bias risks for their automated detection method, definition of outcomes, and type of statistical analyses. Across all the 11 studies, adverse event prevalence ranged from 0% to 17.9%, with a median of 0.8%. The positive predictive value of all triggers to detect adverse events ranged from 0% to 100% across studies, with a median of 40%. Some triggers had wide ranging positive predictive value values: (1) in 6 studies, hypoglycemia had a positive predictive value ranging from 15.8% to 60%; (2) in 5 studies, naloxone had a positive predictive value ranging from 20% to 91%; (3) in 4 studies, flumazenil had a positive predictive value ranging from 38.9% to 83.3%; and (4) in 4 studies, protamine had a positive predictive value ranging from 0% to 60%. We were unable to determine the adverse event prevalence, positive predictive value, preventability, and severity in 40.4%, 10.5%, 71.1%, and 68.4% of the studies, respectively. These studies did not report the overall number of records analyzed, triggers, or adverse events; or the studies did not conduct the analysis.
CONCLUSIONS
We observed broad interstudy variation in reported adverse event prevalence and positive predictive value. The lack of sufficiently described methods led to difficulties regarding interpretation. To improve quality, we see the need for a set of recommendations to endorse optimal use of research designs and adequate reporting of future adverse event detection studies.
Topics: Drug-Related Side Effects and Adverse Reactions; Electronic Health Records; Humans; Patient Safety; Retrospective Studies
PubMed: 29848467
DOI: 10.2196/jmir.9901 -
Value in Health : the Journal of the... Feb 2018To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM).
METHODS
A systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials comparing two or more basal insulin regimens were conducted. The following basal insulin regimens were included: Neutral Protamine Hagedorn (iNPH) (once [od], twice [bid], and four times daily [qid]), insulin detemir (iDet) (od and bid), insulin glargine 100 IU (iGlarg) (od), and insulin degludec (iDegl) (od). We searched the following databases: MEDLINE via OVID, Embase via OVID, and the Cochrane Library (Wiley). Study quality was appraised using Cochrane risk-of-bias checklist for randomized controlled trials. Two outcomes (change in hemoglobin A [HbA] and rate of severe/major hypoglycemia [SH]) were analyzed. Network inconsistency was assessed using Bucher and chi-square tests.
RESULTS
Thirty studies met the eligibility criteria. Twenty-five were included in the HbA network and 16 in the SH network. All studies were of moderate quality. No network inconsistency was evident in the HbA network. Of the seven regimens of interest, iDet (bid) had the highest probability of being best (mean change in HbA -0.48; 95% credible interval -0.69 to -0.29). In contrast, the SH network demonstrated both considerable uncertainty and significant network inconsistency (χ test, P = 0.003).
CONCLUSIONS
Of the specified frequency regimens, iDet (bid) had the highest probability of being the best basal insulin regimen in terms of reduction in HbA. Ranking of the regimens in terms of the SH rate was highly uncertain and no clear conclusion could be made.
Topics: Adult; Bayes Theorem; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Randomized Controlled Trials as Topic
PubMed: 29477399
DOI: 10.1016/j.jval.2017.04.024 -
The Patient Aug 2018Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have...
INTRODUCTION
Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities.
METHOD
A systematic review of multiple databases including Medline, LILACS, Cochrane, and EMBASE databases with several combinations of agreed terms involving randomized controlled trials and cohorts, as well as manual searches and gray literature, was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed.
RESULTS
Eight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (two generic, two mixed, and four specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores, whether as part of subsets or combined into a single score, with the use of GLA versus neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin, but not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the cohort studies scored a maximum on the Newcastle-Ottawa scale for quality, and they generally were of moderate quality with bias in the studies.
CONCLUSION
There was no consistent difference in QoL or patient-reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings.
Topics: Blood Glucose; Brazil; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Patient Satisfaction; Quality of Life
PubMed: 29322308
DOI: 10.1007/s40271-017-0291-3 -
Journal of Cardiothoracic and Vascular... Feb 2018The aim was to evaluate the predictive value of thromboelastometry for postoperative blood loss in adult cardiac surgery with cardiopulmonary bypass. (Review)
Review
OBJECTIVE
The aim was to evaluate the predictive value of thromboelastometry for postoperative blood loss in adult cardiac surgery with cardiopulmonary bypass.
DESIGN
Retrospective cohort study and systematic review of the literature.
SETTING
A tertiary university hospital.
PARTICIPANTS
202 patients undergoing elective cardiac surgery.
INTERVENTIONS
Thromboelastometry was performed before cardiopulmonary bypass and 3 minutes after protamine administration.
MEASUREMENTS AND MAIN RESULTS
The cohort study showed that the preoperative and postoperative thromboelastometric positive predicting value was poor (0%-22%); however, the negative predicting value was high (89%-94%). The systematic review of the literature to evaluate the predictive value of thromboelastometry for major postoperative bleeding in cardiac surgery resulted in 1,311 articles, 11 of which were eligible (n = 1,765; PubMed and Embase, until June 2016). Two studies found a good predictive value, whereas the other 9 studies showed a poor predictability for major postoperative bleeding after cardiac surgery. The overall negative predicting value was high.
CONCLUSIONS
Thromboelastometry does not predict which patients are at risk for major postoperative bleeding.
Topics: Adult; Aged; Aged, 80 and over; Cardiac Surgical Procedures; Cohort Studies; Humans; Middle Aged; Postoperative Hemorrhage; Predictive Value of Tests; Retrospective Studies; Thrombelastography
PubMed: 29126688
DOI: 10.1053/j.jvca.2017.08.025 -
The Journal of Urology Apr 2017We systematically reviewed preclinical and clinical studies on bladder chemodenervation with onabotulinumtoxin A to highlight current limitations and future drug...
PURPOSE
We systematically reviewed preclinical and clinical studies on bladder chemodenervation with onabotulinumtoxin A to highlight current limitations and future drug delivery approaches.
MATERIALS AND METHODS
We identified peer reviewed basic and clinical research studies of onabotulinumtoxin A in the treatment of neurogenic bladder and refractory idiopathic overactive bladder published between March 2000 and March 2016. Paired investigators independently screened 125 English language articles to identify controlled studies on onabotulinumtoxin A administration in the MEDLINE® database and abstracts presented at annual American Urological Association meetings. The review yielded an evidence base of more than 50 articles relevant to the approach of injection-free onabotulinumtoxin A chemodenervation.
RESULTS
The efficacy and safety of intradetrusor injection of onabotulinumtoxin A for the treatment of overactive bladder are sensitive to injection volume and depth, and this issue has motivated researchers to study injection-free modes of drug delivery into the bladder. Urothelial denudation with protamine sulfate or dimethyl sulfoxide, liposome encapsulated onabotulinumtoxin A and other physical approaches are being studied to increase toxin permeability and avoid intradetrusor injections. Liposome encapsulated onabotulinumtoxin A enhances toxin activity while reducing its toxin degradation. The safety and efficacy of liposome encapsulated onabotulinumtoxin A were tested in a multicenter, placebo controlled study. Although this treatment successfully reduced urinary frequency and urgency, it did not significantly reduce urgency urinary incontinence episodes.
CONCLUSIONS
Intradetrusor injection of onabotulinumtoxin A is a safe and effective treatment as reported in several large multicenter, randomized controlled trials. Injection of the toxin into the bladder wall impairs afferent and efferent nerves, but injection-free drug delivery approaches only impair the bladder afferent nerves. Further studies are needed to develop better drug delivery platforms that overcome the drawbacks of intradetrusor injection, increase patient acceptance and reduce treatment costs.
Topics: Botulinum Toxins, Type A; Drug Delivery Systems; Forecasting; Humans; Injections; Liposomes; Nerve Block; Urinary Bladder, Overactive
PubMed: 27871929
DOI: 10.1016/j.juro.2016.11.092 -
Andrology Sep 2016Existing literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between... (Meta-Analysis)
Meta-Analysis Review
Existing literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between the ratio of protamine-1 and protamine-2 with male fertility and the association of protamine deficiency with sperm DNA damage. Quality of available cohort studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a random effects model. The effect of the protamine ratio on male fertility was analyzed in nine studies demonstrating a significantly higher value of the protamine ratio in subfertile men (n = 633) when compared with controls (n = 453, SMD = 0.46, 95% CI 0.25-0.66, Z = 4.42, p < 0.00001). Both protamine mRNA (SMD = 0.45, 95% CI 0.11-0.79, Z = 2.63, p = 0.009) and protein ratio (SMD = 0.46, 95% CI 0.25-0.68, Z = 4.22, p < 0.0001) showed significantly increased values in subfertile patients. The association between protamine deficiency and DNA damage was analyzed in 12 studies (n = 845) exhibiting a combined overall correlation coefficient (COR) of 0.53 (95% CI 0.28-0.71, Z = 3.87, p < 0.001). Protamine deficiency measured by CMA3 staining was significantly associated with sperm DNA damage (COR = 0.71, 95% CI 0.48-0.85, Z = 4.87, p < 0.001), whereas the P1/P2 ratio was not (COR = 0.17, 95% CI -0.16 to 0.46, Z = 0.99, p = 0.33). It is concluded that the protamine ratio represents a suitable biomarker for the assessment of sperm quality and protamine deficiency is closely related with sperm DNA damage.
Topics: DNA Damage; DNA Fragmentation; Humans; Infertility, Male; Male; Protamines; Spermatozoa
PubMed: 27231200
DOI: 10.1111/andr.12216