Heparin and Cancer

1998 ◽  
Vol 80 (07) ◽  
pp. 10-23 ◽  
Author(s):  
Deborah Ornstein ◽  
Leo Zacharski
Keyword(s):  
Clinical Trials ◽  
Unfractionated Heparin ◽  
Cancer Progression ◽  
Randomized Clinical Trials ◽  
Molecular Forms ◽  
Term Survival ◽  
Human Malignancy ◽  
Intensive Investigation ◽  
Cancer Outcome ◽  
Meta Analyses

SummaryHeparin has been the subject of intensive investigation for decades by both basic and clinical scientists because of its usefulness as a therapeutic anticoagulant (1). In addition to its effects on coagulation, however, heparin exhibits many other activities which seem to have little to do with anticoagulation (2). Goerner first observed an effect on the natural history of malignancy in 1930 when he demonstrated that heparin inhibited tumor growth in experimental animals (3). A substantial body of literature on heparin and cancer has developed during the ensuing decades. A recent increase in interest has resulted from observations made during prospective, randomized clinical trials which compared unfractionated heparin (UH) with low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism (VTE). Several studies have shown improvement in short to intermediate term survival in the subset of patients with cancer who received LMWH. This improved outcome has been emphasized in two published meta-analyses (4, 5), and the trend is supported by the results of a more recent prospective study (6). The improved cancer outcome could not be attributed to prevention of VTE in any of the studies; therefore, it is reasonable to hypothesize that a beneficial effect of heparin may be mediated by mechanisms independent of anticoagulation.Heparin has several properties that may plausibly explain its effect on experimental and human malignancy. The purpose of this paper is to summarize the literature on heparin and cancer and review mechanisms by which heparin may exert antineoplastic activity. The goal is to encourage both definitive clinical trials of heparin on cancer outcome and further studies of drug mechanisms in human malignancy. LMWH, with its favorable pharmacokinetic attributes, is suitable for chronic outpatient administration and is an excellent candidate for further investigation. Such a departure from conventional experimental cytotoxic chemotherapy holds promise for development of novel forms of growth regulatory therapy that interrupt pathways of cancer progression. In this review, “heparin” will refer to unfractionated heparin (UH), and “UH” and “LMWH” will be used to distinguish between the two molecular forms.

Rationale for heparin treatment of colon cancer

2000 ◽  
Vol 20 (03) ◽  
pp. 136-142 ◽  
Author(s):  
D. L. Ornstein ◽  
L. R. Zacharski
Keyword(s):  
Clinical Trials ◽  
Substantial Improvement ◽  
Patients With Cancer ◽  
Coagulation Mechanism ◽  
Anticoagulant Drug ◽  
Cancer Outcome ◽  
Meta Analyses ◽  
Improvement In Survival ◽  
Spectrum Of Patients ◽  
To Receive

SummaryIt is widely known that the systemic blood coagulation mechanism is often activated in malignancy, leading to an increased incidence of vascular thromboses in patients with cancer. It is not widely appreciated, however, that products of the coagulation mechanism may also support tumor growth and dissemination. Interest in this approach to cancer therapy has surged recently because of mounting evidence that the familiar anticoagulant drug, heparin, may impede tumor progression. Heparin has the capacity to modify angiogenesis, growth factor and protease activity, immune function, cell proliferation and gene expression in ways that may block malignant dissemination. Clinical trials in which heparin has been administered to a broad spectrum of patients to prevent or treat thrombosis have unexpectedly shown improvement in survival in the subset of patients with malignancy entered to these studies. Meta-analyses of clinical trials comparing unfractionated (UF) versus low molecular weight (LMW) heparin treating venous thromboembolism suggest that there may be substantial improvement in cancer outcome in patients with malignancy randomized to receive LMW heparin. These findings provide a rationale for definitive clinical trials of LMW heparin in cancer, and the results of several such studies that are currently underway are awaited with interest.

scholarly journals Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for nonsystematic adverse events

2019 ◽  
Author(s):  
Evan Mayo-Wilson ◽  
Nicole Fusco ◽  
Hwanhee Hong ◽  
Tianjing Li ◽  
Joseph K. Canner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Selection Criteria ◽  
Randomized Clinical Trials ◽  
Bipolar Depression ◽  
Selective Reporting ◽  
Journal Articles ◽  
Multiple Sources ◽  
Study Results ◽  
Meta Analyses

Abstract Background: Adverse events (AEs) in randomized clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials, or across sources for a single trial, may produce inconsistent and confusing information about the adverse events associated with interventions Methods: We sought to compare the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”) and to determine how selection criteria could impact the AEs reported. We compared sources (e.g., journal articles, clinical study reports [CSRs]) of trials for two drug-indications: gabapentin for neuropathic pain and quetiapine for bipolar depression. We identified selection criteria and assessed how criteria affected AE reporting. Results: We identified 21 gabapentin trials and 7 quetiapine trials. All CSRs (6 gabapentin, 2 quetiapine) reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs that would be reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion, “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.” Conclusions: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on study results. Even if investigators pre-specify selection criteria, selective reporting of AEs will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems we identified in this study. Keywords: Harms, adverse events, clinical trials, reporting bias, selective outcome reporting, data sharing, trial registration

scholarly journals Application of Bee Products for Dermatological Problems

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Heidrun Männle ◽  
Karsten Münstedt
Keyword(s):  
Clinical Trials ◽  
Atopic Dermatitis ◽  
Randomized Clinical Trials ◽  
Case Control ◽  
Health Claims ◽  
Wound Infections ◽  
Herpes Viruses ◽  
Case Control Studies ◽  
Meta Analyses ◽  
Cutaneous Warts

Context: Bee products are frequently suggested as possible treatments for dermatological problems by protagonists of apitherapy, which is a discipline within the field of complementary and alternative medicine. Unfortunately, apitherapists do not support their health claims. This review was to identify potential uses of bee products in the field of dermatology. Evidence Acquisition: Randomized and non-randomized clinical trials, case-control studies, systematic reviews, and meta-analyses on the topics were identified using various search engines. Results: Evidence suggests that bee products may be a reasonable treatment option for wound infections, burns, radiodermatitis, infections with herpes viruses, atopic dermatitis, rosacea, scars, cutaneous warts, acne, psoriasis, facial wrinkles, and intertrigo. Conclusions: There are several applications for bee products in the field of dermatology, for instance treatment of wound infections with honey and herpes infections with propolis.

scholarly journals Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sophie Juul ◽  
Emil Eik Nielsen ◽  
Joshua Feinberg ◽  
Faiza Siddiqui ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Individual Patient Data ◽  
Viral Vector ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Serious Adverse Events ◽  
Meta Analyses ◽  
Harmful Effects

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492

Levosimendan: A Novel Inotropic Agent for Treatment of Acute, Decompensated Heart Failure

2005 ◽  
Vol 39 (11) ◽  
pp. 1888-1896 ◽  
Author(s):  
Grace L Earl ◽  
James T Fitzpatrick
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Mortality Data ◽  
Pharmacokinetic Studies ◽  
Dependent Manner ◽  
Term Survival ◽  
Calcium Sensitizer

OBJECTIVE To review the literature on a novel calcium sensitizer, levosimendan. DATA SOURCES Articles were identified through searches of MEDLINE (1966–June 2005), International Pharmaceutical Abstracts (1970–June 2005), and EMBASE (1992–June 2005) using the key words levosimendan, simendan, calcium sensitizer, calcium sensitiser, and congestive heart failure. STUDY SELECTION AND DATA EXTRACTION Clinical trials and pharmacokinetic studies evaluating the safety and efficacy of levosimendan were selected. DATA SYNTHESIS Levosimendan 6–24 μg/kg intravenous bolus followed by a 24-hour continuous infusion of 0.05—0.2 μg/kg/min improved cardiac output and reduced pulmonary capillary wedge pressure in a dose-dependent manner. Dose-ranging and randomized clinical trials have demonstrated improvement in symptoms and hemodynamics and short-term survival outcomes in the treatment of acute, decompensated heart failure. Clinical trials evaluating retrospective mortality data and combined endpoints (mortality, rehospitalization) have demonstrated better outcomes with levosimendan compared with dobutamine. The incidence of hypotension with levosimendan is not significantly different than with dobutamine, but there is a dose-related increase in heart rate. CONCLUSIONS Levosimendan is useful in moderate to severe low-output heart failure in patients who have failed to respond to diuretics and vasodilators. Based on current studies, levosimendan appears to be a safe alternative to dobutamine for treatment of acute, decompensated heart failure. Prospective clinical trials are needed to confirm the effect of levosimendan on long-term survival and its role in heart failure in the setting of myocardial infarction.

scholarly journals An overview of treatment options for COVID-19

2020 ◽  
Vol 9 (11) ◽  
pp. 1770
Author(s):  
Madhusmita Mohanty Mohapatra ◽  
Manju Rajaram ◽  
Dharm Prakash Dwivedi ◽  
Vishnukant Govindraj ◽  
Pratap Upadhya
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Unknown Origin ◽  
The Novel ◽  
Clinical Trial Registry ◽  
Repurposed Drugs ◽  
Novel Coronavirus ◽  
Meta Analyses ◽  
Effective Drugs

Severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) which emerged in Wuhan initially as pneumonia of unknown origin in December 2019, later spread to whole world and became pandemic on 11th March, 2020. Many drugs have been proposed but are backed without clinical evidence. Scientific bodies are in the row to discover a reliable vaccine and effective drugs against the novel coronavirus. Many antiviral and anti-parasitic drugs which were thought to have some effect on Coronavirus disease 2019 (COVID-19) have been tried during the crisis but none have shown concrete evidence of action. Randomized clinical trials on the repurposed drugs are now registered under clinical trial registry to look at the safety profile and efficacy of the drugs to be used against SARS-CoV-2. Many meta-analyses are being conducted worldwide to frame evidence for the fight against this novel coronavirus. We are providing below a review of various drugs that have been tried for treatment of COVID-19 as well as different clinical trials which are underway.

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