Contamination of aflatoxins as threat to the safety of herbal Unani drugs: an overview

Unani medicine is an oldest system of traditional medicine,where drugs of animal,mineral and herbal origin are used for centuries to cure diseases.Unani remedies are now available not only in drug stores,but also in food stores and super markets.Therefore the efficacy and safety of these drugs is very crucial.One of the most serious risks associated with these remedies is,consumer assumes that they are natural,so they are safe.But biological contamination(bacterial,fungal and insect)of herbal medicines is a serious concern.The Aspergillus flavus and Aspergillus parasiticus are the fungal species that occur naturally,release aflatoxins and is a threat to the natural drugs.The World Health Organization has recommended determination of aflatoxins in natural drugs(Unani)as one of the parameter of their safety studies as Aflatoxin contamination is concerned significantly with health and economic loss affecting humans,animals,and agriculture.Aflatoxin B1 is categorized as a group 1 carcinogen by The International Agency for Research on Cancer that causes a variety of health issues.Thus keeping in mind the deleterious health effects of aflatoxins,here,in this review we have made an attempt to summarize the aflatoxins with respect to their origin,occurrence,structure and properties to generate the awareness among the people dealing mainly with Unani herbal drugs.Besides these their toxicity and effects on health have also been discussed.The analytical methods for their determination and some measures to prevent their contamination are also suggested to improve the efficacy and safety of Unani herbal drugs.

Analysis of the application and practice of PDCA cycle in management of the naked medicine dispensing——the quality and safety of the drug

Objective:To explore the application of plan–do–check–action(PDCA)cycle in the management of the naked medicine dispensing about the automatic package and to analyze the practice improved in the quality of naked medicine dispensing medicine management.Methods:The PDCA theory was used to analyze the data,to find out the causes of the problem,and to formulate the corresponding countermeasures to intervene.The data of the naked medicine/adverse drug events satisfaction degree of the inpatients in 18 inpatient departments given for the adoption of PDCA cycle in January 2017 were set as the observation group.The number of the naked medicine/adverse drug events satisfaction degree of patients in 18 inpatient departments before adoption of PDCA cycle in December 2016 was set as the control group.The number of the naked medicine/adverse drug events satisfaction degree of patients in 18 inpatient departments before and after adoption of PDCA cycle was observed and analyzed.Results:The number of the naked medicine/adverse drug events after implementing the method of PDCA cycle management rate was significantly lower than before the implementation method of PDCA cycle management,and the difference had statistical significance(P<0.05).The satisfaction degree of the inpatients after implementing the method of PDCA cycle management rate was significantly higher than that before the implementation method of PDCA cycle management,and the difference had statistical significance(P<0.05).Conclusion:Application of PDCA cycle in the management of the naked medicine dispensing about the automatic package can help to reduce the adverse drug events,to improve the safety of drug treatment,and to increase the patients’satisfaction degree.

Aging effects on QT interval： Implications for cardiac safety of antipsychotic drugs

Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy： ＂QT interval＂ or ＂QT＂ and ＂age＂ or ＂aging＂. The entry criteria were： over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate （QTc） and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation 〉 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.

“Blind men and an elephant”:The need for animals in research,drug safety studies,and understanding civilizational diseases

Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.

Maligned non-steroidal anti-inflammatory drugs:Misunderstanding of their safety profile in patients with renal insufficiency

Non-steroidal anti-inflammatory drugs have a fundamental and pivotal position in management of many of the disorders managed by rheumatologists.Promulgation of a false perspective of their toxicity has compromised our ability to advise our patients and participate in the management of their disorders. The literature sources, from which the false perspective derives, do not accurately reflect safety and fail to address the value of appropriate drug use monitoring.We, as rheumatologists, must stand up and proactively address engrained misconceptions-if we are to be able to continue to provide safe, effective care for our patients.

Determination of Residues and Safety Analysis of Metal Impurities in Platinum-based Antitumor Drugs

The residual metal impurities in cisplatin, carboplatin and oxaliplatin were determined by ICP-AES. The samples were ignited and dissolved with HCl:HNO 3 (3:1). The method is simple and accurate. By the determination of the metal residues in the samples, the calculated actual daily exposure and concentration of the metal Pd, Ir, Rh, Ru, Mo, Ni, Cr, V, Cu, Mn, Fe and Zn that were less than the permitted daily exposures (PDE) and the limited concentration permitted in the EMEA guideline on the specification limits for residues of metal catalysts or metal reagents [1] . The metal residues can de adequately removed from the active pharmaceutical ingredients and the corresponding drugs. The trace metal residues will not affect human health and lead to the safety hazard by the intravenous injection.

The Impact of a Drug Safety Warning on Discussions between Doctors and Their Patients;the Case of Rosiglitazone

The goal of this study was to track the influence of a highly publicized report on discussions between doctors and their patients and prescribing decisions made in response to concerns about potential medication adverse side effects. This was a retrospective analysis of a primary care network’s electronic medical record database. From a diabetes registry of 12, 246 patients, 329 were identified as taking rosiglitazone prior to the June 14, 2007 release of an article in the New England Journal of Medicine;the article suggesting an increased risk of myocardial events. The entire content of all office visits, telephone messages, and medication lists for each patient were reviewed over a 2-year period subsequent to the article’s publication. Doctor/patient discussions regarding concerns for rosiglitazone were catalogued including the physician’s treatment recommendations. There were documented discussions on rosiglitazone’s potential adverse side effects for 64 patients;19.5 percent of this population. All of the discussions occurred between June 15 and October 30, 2007. Of the entire group, 59.3 percent (N = 195) remained on rosiglitazone. For those advised to continue rosiglitazone, the provider indicated that he/she wanted more data before determining if the drug was not safe or discounted the validity of the safety concerns. For those advised to discontinue rosiglitazone, 112 (83.6 percent) were placed on pioglitazone. An article suggesting potential adverse effects of rosiglitazone resulted in a documented discussion in 19.5 percent of patients on this medication. These findings suggest an awareness of this publication by patients, presumably derived from media reports. However, an awareness of this concern did not result in a substantial change in practice.The majority of patients remained on rosiglitazone. The content of these discussions suggest that most physicians’ recommended waiting for more published data before considering a change. While many factors influence physician’s prescribing behavior, this study demonstrates how a highly publicized report influences the doctor/ patient dialogue.

Drug Usage Safety from Drug Reviews with Hybrid Machine Learning Approach

With the increasing usage of drugs to remedy different diseases,drug safety has become crucial over the past few years.Often medicine from several companies is offered for a single disease that involves the same/similar substances with slightly different formulae.Such diversification is both helpful and danger-ous as such medicine proves to be more effective or shows side effects to different patients.Despite clinical trials,side effects are reported when the medicine is used by the mass public,of which several such experiences are shared on social media platforms.A system capable of analyzing such reviews could be very helpful to assist healthcare professionals and companies for evaluating the safety of drugs after it has been marketed.Sentiment analysis of drug reviews has a large poten-tial for providing valuable insights into these cases.Therefore,this study proposes an approach to perform analysis on the drug safety reviews using lexicon-based and deep learning techniques.A dataset acquired from the‘Drugs.Com’contain-ing reviews of drug-related side effects and reactions,is used for experiments.A lexicon-based approach,Textblob is used to extract the positive,negative or neu-tral sentiment from the review text.Review classification is achieved using a novel hybrid deep learning model of convolutional neural networks and long short-term memory(CNN-LSTM)network.The CNN is used at thefirst level to extract the appropriate features while LSTM is used at the second level.Several well-known machine learning models including logistic regression,random for-est,decision tree,and AdaBoost are evaluated using term frequency-inverse docu-ment frequency(TF-IDF),a bag of words(BoW),feature union of(TF-IDF+BoW),and lexicon-based methods.Performance analysis with machine learning models,long short term memory and convolutional neural network models,and state-of-the-art approaches indicate that the proposed CNN-LSTM model shows superior performance with an 0.96 accuracy.We also performed a statistical sig-nificance T-test to show the significance of the proposed CNN-LSTM model in comparison with other approaches.

Antibody-Drug Conjugates (ADCs): Navigating Four Pillars of Safety, Development, Supply Chain and Manufacturing Excellence

Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poised to revolutionize therapeutics. This paper examines the complexities of ADC production, emphasizing the importance of process characterization and the pivotal role of supply chain characteristics, safety requirements, and Contract Manufacturing Organizations (CMOs) with proficiency. The swift transition of antibody-drug conjugate (ADC) programs from early to advanced clinical stages underscores the urgency for quick and efficient commercial launch preparation. This article delves into strategies to hasten commercial readiness, supply chain strategy, the significance of partnering with adept contract development and manufacturing organizations (CDMOs), and the challenges of ADC production.

Effect on Patient Safety of Brief Interventions Performed by Pharmacists via Drug Profile Books: VISualization of Treatment Assist by pharmacists (VISTA) Project in Japan

In Japanese pharmacies, Drug Profile Books (DPBs), which are a type of Personal Health Record (PHR), are incorporated in order to prevent duplicate medication and drug interactions in outpatients (patients) through the uniform management of drug administration information. In this study, we tried to clarify the effect on patient safety of brief interventions via DPBs by pharmacists. The study design was a randomized controlled trial on pharmacies as clusters. 65 pharmacies agreed to participate in the study (intervention group (IG): 33;control group (CG): 32). The primary outcomes were: rate of inquiry occurrence, rate of prescription change, and rates of duplicate medications & drug interactions. 56 pharmacies (IG: 29;CG: 27) completed the study. There was a higher tendency for prescription changes in the IG compared to the CG (IG: 0.03%;CG: 0.02%;P = 0.08). In addition, the rate of duplicate medications & drug interactions accounting for the inquiries was significantly higher in the IG than in the CG (IG: 89.2%;CG: 71.9%;P = 0.01). This implied that brief interventions by pharmacists using DPBs had an effect in raising patient safety.

The Problems of the Safety Evaluation of Biotechnology Derived Drugs

Recent years have witnessed rapid advances in the toxicologic assessment of biotechproducts.Safety assessment of a biotech product is a complex and multiple process.This includes a knowledge of its pharmaco-biological characteristics,and identifyingthe target patient population and the proposed clinical application. To make a decision on the safe human application(the products are administering tohumans for therapeutic purposes),besides the identity and purity of the final product,

Analysis on Epidemiology Causality Relationship Theory under Food and Drug Safety Context

Violation of food and drug safety and other hazard crimes have the features of long latency and multiple factors. Traditional criminal law causality theory is no controversy to determine causality of criminal responsibility, thus it is necessary to introduce the epidemiology causality theory-it is a kind of causality theory based on epidemic diseases, and it is the high degree of probability in the determination of causality in criminal laws so as to solve the traditional attribution problem, but the theory also exists applicable restriction conditions in judicial practice.

Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Drug Safety Assessment:An Urgent Task

A CAS scientist has pointed out at an international symposium that it is important for China to step up its efforts in drug safety assessment to address a hidden peril in China's pharmaceuticals industry.

Why Don’t We Adequately Identify and Manage Adverse Drug Reactions despite Having the Needed Information?

Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digital/electronic methods could be used to manage this major healthcare problem for individual patients in real time. Methods: We searched the available digital applications and three literature databases using the medical subject heading terms, adverse drug reaction reporting systems or management, filtered by clinical trial or systemic reviews, to detect publications with data about ADR identification and management approaches. We reviewed the reports that had abstract or summary data or proposed or implemented methods or systems with potential to identify or manage ADRs in clinical settings. Results: The vast majority of the 481 reports used retrospectively collected data for groups of patients or were limited to surveying one population group or class of medication. The reports showed potential and definite associations of ADRs for specific drugs and problems, mostly, but not exclusively, for patients in hospitals and nursing homes. No reports described complete methods to collect comprehensive data on ADRs for individual patients in a healthcare system. The digital applications have ADR information, but all are too cumbersome or incomplete for use in active clinical settings. Several studies suggested that providing information about potential ADRs to clinicians can reduce these problems. Conclusion and Relevance: Although investigators and government agencies agree with the need, there is no comprehensive ADR management program in current use. Informing the patient’s healthcare practitioners of potential ADRs at the point of service has the potential for reduction of these complications, which should improve healthcare and reduce unneeded costs.

Appropriateness of Amikacin Dose Prescription, Monitoring and Safety during Hospitalization as an Impact of Clinical Pharmacologist Intervention, in the Israeli Regional Hospital

Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are the analysis of amikacin dose, serum level and the examination of the effectiveness of the clinical pharmacologist (CP) therapeutic drug monitoring (TDM) intervention to guarantee the safety of amikacin use. Methods: This is a one-year retrospective observational chart review study, which evaluates amikacin dose, serum drug level, development of adverse effects in patients on amikacin with or without CP TDM consultation. Results: Amikacin was prescribed for 393 complex patients, with median age 83. Amikacin group (AG) included 140 (32%) courses with CP consultation (AG1) and 292 (68%) courses without CP consultation (AG2). The distribution of most study characteristics in both groups was similar including amikacin dose (9-10 mg/kg/day), renal failure (14%) and mortality (12%). Acceptance for CP consultation was in 46% of amikacin courses and dose changes were done in 63% after CP intervention. Prolonged antibiotic course (4.6 ± 1.5 vs 3.8 ± 1.6 days, p < 0.0001) and the patient’s hemodynamic instability (15% vs 7%, p = 0.01) were more frequent in the AG1 compared to the AG2. There was a strong association between CP consultation and prolonged hospitalization (p = 0.005), while no association between it and amikacin adverse effects, renal failure or mortality. Conclusions: There was no trend to reducing amikacin toxicity, days of hospitaliza tion or mortality in patients with CP consultation. CP TDM intervention was more in the management of complicated clinical situations. However, it is necessary to optimize it.

Work Hard to Ensure Food,Drugs Safety for the People——An interview with Shao Mingli,director-general of the State Food and Drug Administration(SFDA)

Following is an interview given by Shao Mingli, director-general of China＇s State Food and Drug Administration to our reporter on what is being done to ensure food and drug safety in China. As everybody knows, food and drug safety is vital to people＇s lives.

Analysis of the Efficacy,Progression-Free Survival,and Safety of Anlotinib in Advanced Lung Cancer Treatment

Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.

Safety of the long-term use of proton pump inhibitors

The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaff in-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-termuse of PPIs. Long-term use of PPIs does not lead to vitamin B12 def iciencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use longterm in persons in whom there is a clear need for the maintenance of extensive acid inhibition.

Preliminary experience with drug-coated balloon angioplasty in primary percutaneous coronary intervention

We evaluated the clinical feasibility of using drugcoated balloon(DCB) angioplasty in patients undergoingprimary percutaneous coronary intervention(PPCI). Between January 2010 to September 2014,89 STelevation myocardial infarction patients(83% male,mean age 59 ± 14 years) with a total of 89 coronary lesions were treated with DCB during PPCI. Clinical outcomes are reported at 30 d follow-up. Left anterior descending artery was the most common target vessel for PCI(37%). Twenty-eight percent of the patients had underlying diabetes mellitus. Mean left ventricular ejection fraction was 44% ± 11%. DCB-only PCI was the predominant approach(96%) with the remaining 4% of patients receiving bail-out stenting. Thrombolysis in Myocardial Infarction(TIMI) 3 flow was successfully restored in 98% of patients. An average of 1.2 ± 0.5 DCB were used per patient,with mean DCB diameter of 2.6 ± 0.5 mm and average length of 23.2 ± 10.2 mm. At 30-d follow-up,there were 4 deaths(4.5%). No patients experienced abrupt closure of the infarctrelated artery and there was no reported target-lesion failure. Our preliminary experience showed that DCB angioplasty in PPCI was feasible and associated with a high rate of TIMI 3 flow and low 30-d ischaemic event.