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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 -
Annals of Internal Medicine Aug 2018Basal insulin analogues aim for protracted glycemic control with minimal adverse effects. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Basal insulin analogues aim for protracted glycemic control with minimal adverse effects.
PURPOSE
To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM).
DATA SOURCES
Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books.
STUDY SELECTION
Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level <7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues.
DATA EXTRACTION
Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence.
DATA SYNTHESIS
Thirty-nine trials (26 195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300.
LIMITATIONS
Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency.
CONCLUSION
Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300).
PRIMARY FUNDING SOURCE
None. (PROSPERO: CRD42016037055).
Topics: Adult; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Network Meta-Analysis; Risk Assessment
PubMed: 29987326
DOI: 10.7326/M18-0443 -
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 -
Andrologia Jun 2018While several previous studies have proposed an association between male infertility and protamine polymorphism, the reported findings have shown some inconsistency. To... (Meta-Analysis)
Meta-Analysis
While several previous studies have proposed an association between male infertility and protamine polymorphism, the reported findings have shown some inconsistency. To evaluate the potential association between the two most common single nucleotide polymorphisms (rs2301365 and rs1646022) in protamine and male infertility, we performed a meta-analysis involving 2713 cases and 2086 controls from 15 published case-controlled studies. Overall, our analysis showed significant associations between the specific protamine single-nucleotide polymorphism (rs2301365) and male infertility, and this association was indicated by all of the models we tested. Subgroup analysis revealed significant associations with a Caucasian background, PCR sequence, population-based, case size of > 150 and case size of < 150 subgroups. Similarly, significant associations were found between rs1646022 and male infertility in the hospital population and case size of < 200 subgroups. However, trial sequential analysis showed that the number of patients in the study did not reach optimal information size. Further studies with larger sample sizes are now warranted to clarify the potential roles of the two protamine polymorphisms in the pathogenesis of male infertility. This may help us to understand the precise molecular mechanisms underlying the effect of protamines upon male infertility.
Topics: Genetic Association Studies; Genetic Predisposition to Disease; Humans; Infertility, Male; Male; Polymorphism, Single Nucleotide; Protamines; Spermatozoa
PubMed: 29537099
DOI: 10.1111/and.12990 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2018While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically...
INTRODUCTION
While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into "definite", "likely", "possible", or "unlikely" to cause pulmonary arterial hypertension, based on the strength of evidence.
OBJECTIVE
This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension.
METHODS
A systematic search was conducted using PubMed covering the period September 1970- 2017. The search term utilized was "drug induced pulmonary hypertension". This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism. Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension. Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection. Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear. Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension. Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents; nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports. Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension. Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes. Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects.
CONCLUSIONS
Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an individual to PAH have yet to be elucidated.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Hypertension, Pulmonary; Muscle, Smooth, Vascular; Prescription Drugs
PubMed: 29508628
DOI: 10.1080/15563650.2018.1447119 -
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 -
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