Clinical Implications of Kratom (Mitragyna speciosa) Use: a Literature Review.

Purpose of Review: This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications. Recent Findings: A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs. A randomized controlled trial has further supported kratom's therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings. Summary: Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed.

A Comparison of Acute Neurocognitive and Psychotomimetic Effects of a Synthetic Cannabinoid and Natural Cannabis at Psychotropic Dose Equivalence.

Due to differences in potency, efficacy, and affinity for CB1 receptors, similarities and differences in psychoactive effect profiles of natural cannabis and synthetic cannabinoids (SCs) cannot reliably be derived from equipotent dose comparisons. Instead, the current study proposes to compare the intrinsic psychoactive effects of natural cannabis (THC) and an SC, JWH-018, at psychotropic dose equivalence. Participants from two placebo-controlled studies were matched for their levels of subjective high to compare neurocognitive and psychotomimetic effects of THC and JWH-018. At equal subjective intoxication levels, both drugs impaired psychomotor, divided attention, and impulse control, with no significant difference between the two drugs. Both drugs also caused significant psychotomimetic effects, but dissociative effects were considerably more pronounced for JWH-018 than THC. We conclude that psychotropic dose equivalence provides a uniform approach for comparing the neurocognitive and psychotomimetic profiles of CB1 agonists, which can also be applied to other drug classes.

A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.

INTRODUCTION: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption. OBJECTIVE: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans. METHODS: A systematic literature search using PubMed and the Medline database was conducted between April and November 2020. RESULTS: Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal). CONCLUSIONS: Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required.

Minority Participation in Biobanks: An Essential Key to Progress.

Biobanks are critical resources for biomedical research and will be a driving force behind personalized medicine. Although biobanking efforts are increasing across the USA and the world, minority populations are frequently underrepresented in biobanks, which undermines their value. A number of factors have been linked to low rates of minority participation in biobanks, including mistrust of researchers, concerns about privacy and confidentiality, logistical barriers to participation, and inadequate opportunities to participate. There are several strategies biobankers can use to increase participation of minority and underserved populations and optimize the value of their biospecimen collection for research.

Cancer information seekers in china: a preliminary profile.

Cancer is now the leading cause of death in China. Effective communication about cancer risk and prevention is an important component of cancer control. Yet, research in this area is very limited in China. This study used probability sample survey data from 2 Chinese cities (Beijing and Hefei, Anhui Province) to investigate potential predictors of self-initiated cancer information seeking. Analysis showed that cancer information seekers in China were likely to be married, relatively educated, earning modest incomes, living in rural areas, smoking occasionally, having a family cancer history, relatively trusting of the media for health information, somewhat knowledgeable about cancer, having nonfatalistic attitudes about cancer, and seeing a personal need for more cancer information. The pattern of results, particularly the lack of influence of personal health and risk perception factors, highlights the possibility that seeking for others might be more prevalent than seeking for self in China. Overall, findings suggest that emphasizing family need and mobilizing family support might be a productive approach to cancer communication interventions in China.

Absolute and comparative cancer risk perceptions among smokers in two cities in China.

INTRODUCTION: Knowledge about health effects of smoking motivates quit attempts and sustained abstinence among smokers and also predicts greater acceptance of tobacco control efforts such as cigarette taxes and public smoking bans. We examined whether smokers in China, the world's largest consumer of cigarettes, recognized their heightened personal risk of cancer relative to nonsmokers. METHODS: A sample of Chinese people (N = 2,517; 555 current smokers) from 2 cities (Beijing and Hefei) estimated their personal risk of developing cancer, both in absolute terms (overall likelihood) and in comparative terms (relative to similarly aged people). RESULTS: Controlling for demographics, smokers judged themselves to be at significantly lower risk of cancer than did nonsmokers on the comparative measure. No significant difference emerged between smokers and nonsmokers in absolute estimates. CONCLUSIONS: Smokers in China did not recognize their heightened personal risk of cancer, possibly reflecting ineffective warning labels on cigarette packs, a positive affective climate associated with smoking in China, and beliefs that downplay personal vulnerability among smokers (e.g., I don't smoke enough to increase my cancer risk; I smoke high-quality cigarettes that won't cause cancer).

Changing the way we do business: recommendations to accelerate biomarker development in pancreatic cancer.

Pancreatic ductal adenocarcinoma is the most aggressive of all epithelial malignancies. In contrast to the favorable trends seen in most other common malignancies, the five-year survival of patients with this disease remains only 6%, a statistic that has changed minimally for decades. Only two drugs have been approved by the U.S. Food and Drug Administration (FDA) for use in pancreatic cancer in the last 15 years, and there are no established strategies for early detection.

A case-control study estimating accident risk for alcohol, medicines and illegal drugs.

BACKGROUND: The aim of the present study was to assess the risk of having a traffic accident after using alcohol, single drugs, or a combination, and to determine the concentrations at which this risk is significantly increased. METHODS: A population-based case-control study was carried out, collecting whole blood samples of both cases and controls, in which a number of drugs were detected. The risk of having an accident when under the influence of drugs was estimated using logistic regression adjusting for gender, age and time period of accident (cases)/sampling (controls). The main outcome measures were odds ratio (OR) for accident risk associated with single and multiple drug use. In total, 337 cases (negative: 176; positive: 161) and 2726 controls (negative: 2425; positive: 301) were included in the study. RESULTS: Main findings were that 1) alcohol in general (all the concentrations together) caused an elevated crash risk; 2) cannabis in general also caused an increase in accident risk; at a cut-off of 2 ng/mL THC the risk of having an accident was four times the risk associated with the lowest THC concentrations; 3) when ranking the adjusted OR from lowest to highest risk, alcohol alone or in combination with other drugs was related to a very elevated crash risk, with the highest risk for stimulants combined with sedatives. CONCLUSION: The study demonstrated a concentration-dependent crash risk for THC positive drivers. Alcohol and alcohol-drug combinations are by far the most prevalent substances in drivers and subsequently pose the largest risk in traffic, both in terms of risk and scope.

Knowledge exchange--translating research into practice and policy.

Substantial differences in population-based cancer control outcomes exist within and between nations. Optimal outcomes derive from 'what we know', 'what we apply in practice', and 'how complete and compliant is the population uptake of public health and clinical practice change'. This continuum of research (scientific discovery) to practice (application and uptake) to policy impacts the speed and completeness of practice change and is greatly influenced by the ability, opportunity and readiness of countries to implement evidence informed practices and policies through innovative change. Session 4 of the 4th International Cancer Control Congress focused on knowledge exchange through three plenary presentations and five interactive workshop discussions: 1) the role of epidemiological data as a basis for policy formulation; 2) existing global frameworks for cancer control; 3) knowledge exchange as it relates to public health practice and policy; 4) knowledge exchange in relation to primary, community, and specialist cancer care; and 5) the role of public engagement and advocacy in influencing cancer control policy. Common themes emerging from workshop discussions included the recognition of the importance of knowledge exchange processes, constituents and forums as key aspects of preparedness, awareness and readiness to implement public health and clinical practice change. The importance of cultural and contextual differences between nations was identified as a challenge requiring development of tools for generating relevant population/societal data (e.g., projection methodologies applied to population demographics, outcomes and resources, both societal, human and fiscal) and capacity building for facilitating knowledge transfer and exchange between the constituencies engaged in population-based public health practice and clinically based primary care and disease specialty practice exchange (researchers, health practitioners, health administrators, politicians, patients and families, and the private and public sectors). Understanding patient and public engagement advocacy and its role in influencing health and public policy investment priorities emerged as a critical and fundamental aspect of successful implementation of evidence-informed cancer control change.

Thrombin-activatable fibrinolysis inhibitor is activated in vivo in a baboon model of Escherichia coli induced sepsis.

Activated thrombin-activatable fibrinolysis inhibitor (TAFIa or CPU) is a carboxypeptidase that is able to attenuate fibrinolysis. Although its role in fibrinolysis and inflammation has been studied extensively in vitro, its levels and subsequent effect in vivo has not been studied to the same extent. Using our recently developed assay that is specific for TAFIa, we were able to quantify its levels in plasma samples obtained from an Escherichia coli (E. coli) challenged baboon sepsis model. TAFIa levels accumulated appeared to be E. coli dose dependent, where the lethal dose of 10(10) CFU/kg generated a peak TAFIa level of 24 nM by 2 h, which represents almost 32% of total plasma level of its precursor, thrombin-activatable fibrinolysis inhibitor (TAFI or proCPU). Furthermore, our data suggest that there is continual TAFI activation under lethal level of E. coli as the apparent half-life of TAFIa is increased from 8 min to 2.2 h. Two sublethal doses of 10(8) and 10(6) CFU/kg generated peak TAFIa levels of 1.1 and 0.4 nM, respectively, both by 6 h. Taken together, our data show that TAFIa is generated at systemic levels, in a dose-dependent manner, that can substantially affect both fibrinolysis and inflammatory response in the E. coli challenged baboon sepsis model.

Biospecimen Reporting for Improved Study Quality.

Human biospecimens are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues, it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The Biospecimen Reporting for Improved Study Quality guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected.

Biospecimen reporting for improved study quality (BRISQ).

Human biospecimens are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues, it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected.

Biospecimen reporting for improved study quality (BRISQ).

Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected.

NIH state-of-the-science conference statement: Enhancing use and quality of colorectal cancer screening.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on enhancing use and quality of colorectal cancer screening. PARTICIPANTS: A non-DHHS, nonadvocate 13-member panel representing the fields of cancer surveillance, health services research, community-based research, informed decision-making, access to care, health care policy, health communication, health economics, health disparities, epidemiology, statistics, thoracic radiology, internal medicine, gastroenterology, public health, end-of-life care, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the RTI International-University of North Carolina Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: The panel found that despite substantial progress toward higher colorectal cancer screening rates nationally, screening rates fall short of desirable levels. Targeted initiatives to improve screening rates and reduce disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. This could be achieved by utilizing the full range of screening options and evidence-based interventions for increasing screening rates. With additional investments in quality monitoring, Americans could be assured that all screening achieves high rates of cancer prevention and early detection. To close the gap in screening, this report identifies the following priority areas for implementation and research to enhance the use and quality of colorectal cancer screening: • Eliminate financial barriers to colorectal cancer screening and appropriate follow up. • Widely implement interventions that have proven effective at increasing colorectal cancer screening, including patient reminder systems and one-on-one interactions with providers, educators, or navigators. • Conduct research to assess the effectiveness of tailoring programs to match the characteristics and preferences of target population groups to increase colorectal cancer screening. • Implement systems to ensure appropriate follow-up of positive colorectal cancer screening results. • Develop systems to assure high quality of colorectal cancer screening programs. • Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings.

The development and deployment of Common Data Elements for tissue banks for translational research in cancer - an emerging standard based approach for the Mesothelioma Virtual Tissue Bank.

BACKGROUND: Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) - compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC). METHODS: The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML). RESULTS: Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data including block level annotation, and follow-up data including treatment, recurrence and vital status. The end result of such an effort would eventually provide an increased sample set to the researchers, and makes the system interoperable between institutions. CONCLUSION: The CAP, ADASP and the NAACCR elements represent widely established data elements that are utilized in many cancer centers. Herein, we have shown these representations can be combined and formalized to create a core set of annotations for banked mesothelioma specimens. Because these data elements are collected as part of the normal workflow of a medical center, data sets developed on the basis of these elements can be easily implemented and maintained.

Thrombin-activable fibrinolysis inhibitor zymogen does not play a significant role in the attenuation of fibrinolysis.

Activated thrombin-activable fibrinolysis inhibitor (TAFIa) plays a significant role in the prolongation of fibrinolysis. During fibrinolysis, plasminogen is activated to plasmin, which lyses a clot by cleaving fibrin after selected arginine and lysine residues. TAFIa attenuates fibrinolysis by removing the exposed C-terminal lysine residues. It was recently reported that TAFI zymogen possesses sufficient carboxypeptidase activity to attenuate fibrinolysis through a mechanism similar to TAFIa. Here, we show with a recently developed TAFIa assay that when thrombin is used to clot TAFI-deficient plasma supplemented with TAFI, there is some TAFI activation. The extent of activation was dependent upon the concentration of zymogen present in the plasma, and lysis times were prolonged by TAFIa in a concentration-dependent manner. Potato tuber carboxypeptidase inhibitor, an inhibitor of TAFIa but not TAFI, abolished the prolongation of lysis in TAFI-deficient plasma supplemented with TAFI zymogen. In addition, TAFIa but not TAFI catalyzed release of plasminogen bound to soluble fibrin degradation products. The data presented confirm that TAFI zymogen is effective in cleaving a small substrate but does not play a role in the attenuation of fibrinolysis because of its inability to cleave plasmin-modified fibrin degradation products.

An assay for measuring functional activated thrombin-activatable fibrinolysis inhibitor in plasma.

Thrombin-activatable fibrinolysis inhibitor (TAFI), also called procarboxypeptidase U (proCPU), is a plasma zymogen that can be activated by thrombin, the thrombin-thrombomodulin complex, or plasmin. The activated form of TAFI (TAFIa, CPU) removes C-terminal lysine residues of plasmin-modified fibrin (FN') that mediates a positive feedback mechanism in plasminogen (Pg) activation, thereby attenuating fibrinolysis. The plasma concentration of TAFI is approximately 75 nM. Because the half-maximal effect of TAFIa occurs at 1 nM, only approximately 1.3% of TAFI needs to be activated to exert an effect on clot lysis. The assay is performed by mixing soluble FN' covalently attached to a quencher and fluorescein-labeled Pg. The sample containing TAFIa is then added, and the rate of fluorescence increase due to removal of C-terminal lysine from FN' and loss of Pg binding is measured with a fluorescence plate reader. The assay was shown to be sensitive for TAFIa at a concentration as low as 12 pM. The intraassay variability and interassay variability of the assay were 6.3 and 8.3%, respectively. This assay was not confounded by the naturally occurring TAFI Thr325Leu polymorphism that affects the thermal stability of TAFIa or endogenous plasminogen in plasma.