Drugs In Medical Practice Research Articles

МЕЖДУНАРОДНЫЙ ПРОФИЛЬ БЕЗОПАСНОСТИ ПРИМЕНЕНИЯ ОМАЛИЗУМАБА В КЛИНИЧЕСКОЙ ПРАКТИКЕ

The article provides an overview of information on cases of adverse reactions with the use of omalizumab, the reports of which are included in the database of the World Health Organization's international drug monitoring program in 6 years (selected period 01.01.2017-01.01.2024). An analysis of the safety indicators of omalizumab, which is the drug of choice in the treatment of a number of severe atopic diseases, was carried out. Despite the long-term use of the drug in medical practice (more than 15 years) and reports on its efficacy, there is insufficient information on adverse reactions during its use, especially in the Russian Federation, since long-term clinical monitoring has not been carried out. The obtained characteristics of the structure of adverse reactions to the use of omalizumab by gender, age of patients, nature of their complaints, severity of outcomes, geography and initiators of reports, constitute a theoretical basis for improving and fine-tuning the domestic system of pharmacovigilance and drug monitoring, and may also be of practical interest to doctors, researchers and health regulators. The first rank places in the structure of adverse reactions to omalizumab are occupied by: general disorders and reactions at the site of administration, disorders of the skin and subcutaneous tissue, disorders of the respiratory system, thoracic and mediastinal organs, injuries, intoxication and complications of procedures, disorders of the nervous system. In the overall structure of NR, serious adverse reactions to omalizumab accounted for 35,1%. The analysis showed that in the assessment of adverse reactions, a significant role is given to patients (their representatives), whose opinion is determined by subjective feelings and the level of awareness, so more attention should be paid to drug informing patients.

Drug-induced Liver Injury Caused by Levetiracetam

Levetiracetam, known as Keppra, is an antiepileptic drug that is commonly used due to its rare side effects, particularly on the liver. It is mainly excreted by the kidneys with minimal hepatic metabolism. Drug-induced liver injury associated with Levetiracetam is extremely rare. Few cases of Levetiracetam-induced liver toxicity and failure were declared. Until now, there are no previously reported cases of mixed pattern liver injury related to this drug. We report a case of a patient taking Levetiracetam, that was found to have mixed pattern liver injury. Our patient experienced important rapid improvement of hepatocellular injury and a delayed improvement of cholestatic pattern after Levetiracetam discontinuation, suggesting the mentioned association. This case report is the first to establish both hepatocellular and cholestatic injury associated with Levetiracetam. We would like to highlight this side effect, though rare, of this frequently used drug in medical practice.

The use of statin drugs in medical practice. Literature review

Relevance. Simvastatin is a statin drug used for the clinical control of hypercholesterolemia. Over the past decades, there has been a steady increase in the number of studies on the possibilities of simvastatin, in many respects superior to the effect of lowering blood cholesterol levels. The use of simvastatin in the field of bone tissue regeneration, as well as its ability to reduce the inflammatory response, is being actively investigated.The purpose of the review: to consider modern ideas about simvastatin and to study its pleiotropic effects.Materials and methods. The analysis of scientific publications in the electronic databases eLIBRARY, PubMed and Google Scholar (articles, meta-analyses, systematic reviews) for the time interval from 2015 to 2022 was carried out. Materials containing information on the hypocholes-terolemic activity of simvastatin and its mechanism of action, the use of simvastatin in periodontal practice, as well as the osteoinductive effect of simvastatin and its use in bone engineering are included.Results. The review reviewed 83 articles, from which 53 articles were selected after reviewing the literature.Conclusion. Based on the analyzed data, it can be concluded that the effects of simvastatin are multifaceted. Its anti-inflammatory activity has been proven by inhibiting interleukins and inflammatory mediators, participation in bone tissue regeneration by gene expression and stimulation of osteoblast cell differentiation.

Современный взгляд на проблему влияния противоэпилептических препаратов на статус витамина D (клинический случай с обзором литературных источников)

В данной статье представлены клинический случай влияния противоэпилептических препаратов (ПП) на уровень витамина D (в частности, длительного приема препарата вальпроата натрия) и современные данные зарубежных публикаций по этой проблеме. Как известно, существует перечень лекарственных препаратов, отрицательно влияющих на метаболизм витамина D. В частности, к препаратам, снижающим всасывание витамина D, относят препараты для лечения эпилепсии. Противоэпилептические средства — это лекарственные препараты различного происхождения, используемые для предотвращения или уменьшения судорог, соответствующих им эквивалентов (потеря или нарушение сознания, поведенческие и вегетативные нарушения и др.), которые наблюдаются при периодически возникающих приступах различных форм эпилепсии. Широкое применение в медицинской практике данных лекарственных препаратов требует изучения их возможных побочных реакций и проведения своевременной их коррекции, поскольку иностранные источники указывают на то, что ПП усиливают дефицит витамина D и ухудшают симптомы при проксимальной миопатии, что требует обязательной медикаментозной коррекции препаратами витамина D; пациенты, страдающие эпилепсией, имеют дефицит витамина D; хроническая терапия вальпроатами связана с более низкими показателями минеральной плотности костной ткани у молодых пациентов с эпилепсией. Данный клинический случай показал, как длительный прием вальпроата натрия привел к развитию у пациентки вторичного системного остеопороза и дефицита витамина D, о чем свидетельствуют результаты лабораторных и инструментальных исследований, а отмена врачом противоэпилептического препарата и назначение препарата витамина D3 улучшили общее состояние больного и нормализовали уровень данного витамина в сыворотке крови. На основании данных литературного обзора и собственных наблюдений, в частности клинического случая, можно сделать вывод, что пациенты, которые страдают эпилепсией и принимают ПП, должны получать препараты витамина D3 в целях предотвращения развития остеопороза и дефицита данного витамина.

MOLECULAR DESIGN OF N-ACYL DERIVATIVES OF 2-(2-OXOPYROLIDIN-1-YL)-ACETAMIDE WITH GABA-ERGIC AND GLUTAMATERGIC ACTIVITIES

The first of the most successfully implemented nootropic drugs in medical practice is piracetam, which should be attributed to cyclic derivatives of gamma-aminobutyric acid. The production of new piracetam derivatives with high nootropic activity is a promising direction in the development of new neuroprotective drugs.The aim of the study is to predict GABA-ergic and glutamatergic activities of N-acyl derivatives of 2-(2-oxopyrolidin-1-yl)- acetamide by a molecular docking method through the energy analysis of interaction of modeled structures with GABAA and AMPA receptors with their subsequent targeted synthesis.Materials and methods. The objects of the research are new N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide and a virtual model of the GABAA receptor of the Homo sapiens organism with the identification code 6D6U and a three-dimensional model of the AMPA-receptor of the Rattus norvegicus organism with the identification code 3LSF from the RCSB PDB database. The simulated compounds were designed in the HyperChem 8.0.8 program. This program was also used to optimize geometry using the force field of molecular mechanics MM+. Molecular docking was carried out using the Molegro Virtual Docker 6.0.1 program. The preparation of N-acyl derivatives of 2-(2-oxopyrrolidin-1-yl)-acetamide was carried out by the interaction of 2-(2-oxopyrrolidin-1-yl)-acetamide with an excess of the corresponding anhydride under conditions of acid catalysis.Results. Based on the results of molecular docking, a high affinity of all simulated compounds for the binding site of GABAA and AMPA receptors can be estimated. According to the predict, the maximum GABA-ergic activity should be expected for (N-[2-(2-oxopyrrolidin-1-yl)-acetyl]-butyramide. N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide form a more stable complex with amino acid residues Arg207, Phe200, Thr202, Tyr97, Tyr157, Tyr205 and Phe65 of the GABAA receptor binding site than the GABA molecule. In terms of the minimum interaction energy, the N-acyl derivatives of 2-(2-oxopyrrolidin-1-yl)- acetamide are superior to a number of known ligands such as GABA, piracetam, anipiracetam, picamilon and pramiracetam. The tested compounds have also shown a high affinity for the binding site of the AMPA receptor. The leader compound is also the compound PirBut, as in the case of the GABAА receptor.Conclusion. Molecular modeling of the ligands interaction with the active binding site of gamma-aminobutyric acid of the GABAA receptor by molecular docking showed that all virtual N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide can exceed a number of nootropic drugs by activity. In the course of molecular design, a method for predicting a glutamatergic activity for 2-pyrrolidone derivatives has been developed. It suggests a significant nootropic activity for N-[2-(2-oxopyrrolidin-1-yl)- acetamide amides.

Comparative studies of the kinetics of dissolution of medicines on the basis of clopidogrel

Generic medicines occupy dominant positions both in the pharmaceutical market of Ukraine and in industrial production by domestic pharmaceutical enterprises. The use of generic drugs in medical practice is of significant medical and social importance for expanding the accessibility of the general population to essential drugs. In Ukraine, more than twenty generic medicines based on clopidogrel, both foreign and domestic, are registered. All generic drugs containing clopidogrel bisulfate must comply with pharmaceutical bisulfate must comply with pharmaceutical equivalence, the kinetics of release of the active pharmaceutical ingredient using the Dissolution test in vitro, and pharmacokinetic parameters in vivo.
 The aim of the work was to carry out comparative studies of the dissolution kinetics of four samples of generic drugs based on clopidogrel with the dissolution kinetics of the original drug Plavix®, to evaluate the similarity factor of dissolution profiles and to determine the effect of biopharmaceutical factors on the equivalence of generics. Comparative studies of the kinetics of dissolution were carried out by the in vitro method according to the «Dissolution» test using a device with a blade with a
 rotation speed of 50 rpm, a dissolution medium with a pH value of 2.0 in a volume of 900 ml at a temperature of 37 ± 1 °C. The determination of the quantitative content of clopidogrel, which passed into the dissolution medium, was carried out by the method of adsorption spectrophotometry in the ultraviolet region at a wavelength of
 about 240 ± 2 nm. Based on the data obtained, the dissolution profiles of the original drug Plavix® and the studied samples of generic drugs were constructed, the similarity of which was assessed by the value of the similarity factor. According to the research results, it was found that one sample of the generic drug proved its equivalence by the in vitro method to Plavix®, and three other samples of generics had differences in dissolution kinetics in comparison with the original drug. Biopharmaceutical factors were analyzed that could affect the dissolution kinetics of the studied generic drugs, from which the physicochemical characteristics of clopidogrel bisulfate, the qualitative and quantitative composition of excipients and the features of the technological process were determined.
 Thus, on the basis of the comparative studies of the dissolution kinetics of drugs based on clopidogrel, generics were found that did not correspond to the in vitro equivalence according to the Dissolution test to the original drug, which could be due to the influence of a combination of biopharmaceutical factors.

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet-Hydrogel Frameworks.

The promising potential of bioorthogonal catalysis in biomedicine is inspiring incremental efforts to design strategies that regulate drug activity in living systems. To achieve this, it is not only essential to develop customized inactive prodrugs and biocompatible metal catalysts but also the right physical environment for them to interact and enable drug production under spatial and/or temporal control. Toward this goal, here, we report the first inactive precursor of the potent broad-spectrum anticancer drug paclitaxel (a.k.a. Taxol) that is stable in cell culture and labile to Pd catalysts. This new prodrug is effectively uncaged in cancer cell culture by Pd nanosheets captured within agarose and alginate hydrogels, providing a biodegradable catalytic framework to achieve controlled release of one of the most important chemotherapy drugs in medical practice. The compatibility of bioorthogonal catalysis and physical hydrogels opens up new opportunities to administer and modulate the mobility of transition metal catalysts in living environs.

Application of Phagotherapy in the Treatment of Burn Patients (Review).

Treatment of patients with a burn injury is a complex process involving multicomponent multidirectional intensive therapy of the majority of organs and systems damaged by thermal effects on the skin, alternating with repeated surgical interventions aimed at removing nonviable tissues with subsequent plastic closure of wound defects. After the recovery from the burn shock, local infectious complications are considered to be the leading problem that decelerates the process of recovery and is the main cause of lethal outcomes. Since the skin integrity is broken, microorganisms penetrate readily into the internal environment of the human organism resulting in a septic state with multiple organ failure. A widespread and often uncontrollable use of antibacterial drugs in medical practice has led to the emergence of multiple drug resistance (MDR) in microorganisms.Introduction of drugs made on the basis of bacteriophages into practice is presently becoming increasingly important. This is confirmed by the growing interest in this field of pharmacology, the development of special programs aimed at studying the processes of phage and bacterial cell interaction.This review presents the main types of bacteria pertaining to MDR pathogens, principles of their classification, and the risk factors for infecting patients. The mechanisms of the selective action of phage particles on a bacterial cell and the possibility of using phage therapy in the treatment of burn injury (experimental and clinical data) based on the analysis of foreign literature are demonstrated as well as new positive properties of phages related to the changes in the macroorganism immune status caused by the interaction with bacteriophage particles.

Biomedical Cell Products or High-Tech Drugs?

Marketing authorisation is a prerequisite for the use of drugs in medical practice in the Russian Federation. The marketing authorisation procedure is applicable to ordinary medicinal products. As for advanced therapy medicinal products containing viable human cells — there are currently two authorisations pathways: athorisation of biomedical cell products (BCPs) at the national level according to the Federal Law No. 180-FZ «On biomedical cell products», and authorisation of high-technology drugs (HTDs) in the Eurasian Economic Union (EEU). The production, pre-clinical and clinical studies, expert evaluation and marketing authorisation procedures are regulated by different legal acts and differ significantly. The aim of the study was to perform comparative analysis of concepts, terms, production process requirements, designs of pre-clinical and clinical studies, and the marketing authorisation procedures for BCPs as defined in the Russian and EEU legislation. It should be noted that both the Federal Law No. 180-FZ and the EEU legislative framework are not currently used due to the lack of such drugs (somatic cell-based BCPs or HTDs). Therefore, at present, the choice of the procedure of obtaining marketing authorisation for drugs containing viable human cells has to be made by the manufacturer, until the Russian and EEU legal frameworks become harmonised.

Методические подходы к разработке структурно-логической схемы персонализированного подбора лекарственных препаратов для онкологических больных

The article investigated the issues of the arrangement of personalized selection of drugs for cancer patients. The potential economic efficiency of the use of molecular genetic studies for the prescription of drugs and the cost-effectiveness was calculated using antitumor drugs as an example. A sociological survey of medical professionals on personalized selection of drugs in medical practice was conducted. A statistical link has been established between the practice of prescribing drugs according to the pharmacogenetic testing results and such indicators as side effects monitoring, pharmacoeconomic analysis of the use of drugs in medical organizations. The structural-logical scheme of interaction between the subjects of healthcare and the drug provision system for personalized therapeutic drug management for cancer patients has been developed based on scientific research.

Iodinated Contrast Media in Pediatric Cardiac Angiography Nephrotoxic risk evaluation

Contrast agents are among the most frequently used drugs in medical practice. The aim of our study was to evaluate the incidence of complications associated with the use of different contrast agents in an angiography lab dedicated to pediatric patients with congenital heart disease. Between June 2015 and December 2017, 166 patients with congenital heart disease were diagnosed and/or treated in the angiography lab. Of these patients, 38 were excluded because they did not require contrast substance administration. As interventional procedures we performed pulmonary valvular dilatation in 17 cases (10.2%), stent implantation in coarctation of the aorta in 9 cases (5.4%), PDA closure in 62 cases (37.3%), atrial septal defect (ASD) closure in 36 patients (including patients without contrast agent�s administration) (21.7%). In the group of 129 patients who received contrast agents, the median age was 5.8 years (range 0.1-19 years) and median weight 22.8 kg (range 2.8-72 kg). Average consumption of contrast media per procedure was 79 ml/procedure (range 5 - 400 mL) and 4.3 mL/kg (range 0.4 - 22.7). We used iomeprol (24%), iohexol (8.5%), iopromide (67.4%). No contrast related complications are reported in this group. In conclusion, the contrast agents we used seem to be safe and are not associated with renal complications.

STATISTICAL EVALUATION OF THE EFFECTIVENESS OF THE USE OF DRUGS

В статье рассматриваются проблемы анализа целесообразности внедрения лекарственных препаратов во врачебную практику. Раскрывается метод построения математической модели реального экономического процесса. Методом статистической проверки статистических гипотез проводится оценка эффективности построенной математической модели. Доказывается, что лечение пациентов экспериментальной группы за счет приема лекарственного средства является эффективным. Это позволяет говорить о целесообразности внедрения данного препарата в лечебную практику. Для принятия окончательного решения необходимо оценить эффективность препарата по сравнению с аналогами. Цель: оценка целесообразности внедрения лекарственных препаратов в лечебную практику. Метод или методология проведения работы: в статье использовался метод статистической проверки статистических гипотез. Результаты: получено подтверждение целесообразности использования лекарственного препарата в лечебной практике. Область применения результатов: полученные результаты рекомендуется применять при оценке целесообразности использования лекарственного препарата.

Synthesis, physical and chemical properties of 5-(adamantane-1-yl)-4-amino-1,2,4-triazole-3-thiol derivatives

Implementation of new highly efficient drugs in medical practice is one of the most urgent problems of modern pharmaceutical industry. Scientific achievements of heterocyclic compounds’ chemistry clearly show that 1,2,4-triazole system is promising object of such research. It should be also noted that compounds, with adamantane core deserve special attention.The aim of our work was to synthesize new derivatives of 5-(adamantan-1-yl)-4-amino-1,2,4-triazole-3-thiols, and to investigate their physical and chemical properties.Materials and methods. Chemical names of compounds are given in accordance with IUPAC nomenclature (1979) and the IUPAC recommendations (1993). Study of physical-chemical properties of obtained compounds was carried out in accordance with methods listed in the State Pharmacopia of Ukraine. Melting point was determined on the automatic device for determining the melting temperature Stanford Research Systems OptiMelt MPA100 (manufacturing USA). Elemental composition of new compounds was established on the elemental analyzer Elementar Vario EL cube (CHNS) (standard – sulfanilamide). The data of elemental analysis correspond to the calculated one. 1H NMR spectra of compounds were recorded using spectrometer Mercury 400. Chromato-mass spectra were recorded on a spectrometer Agilent 6890N/5973N/FID production of Agilent Technologies.Results. The concept of creating biologically active molecules is first of all directed on combining fragments of different molecules in one. Theoretically, this could lead to the new types of compounds with pharmacological action, and sometimes to the potentiation of existing biological properties. Further actions are focused on the physical and chemical properties study of these compounds. To establish the structure of 5-(adamantan-1-yl)-4-((aryl-, heteryl)ilyden)-amino-1,2,4-triazole-3-thiols we used an integrated approach with the use of modern physical and chemical methods of analysis. Individuality of compounds in each case is confirmed by chromatography. The results of the chromatographic investigations showed that in all cases the constants of pseudo molecular ions peaks of obtained 5-(adamantan-1-yl)-4-((aryl-, heteryl)yliden)amino-1,2,4-triazole-3-thiols coincide with theoretical calculations of molecular masses.Conclusions. New 5-(adamantan-1-yl)-4-((aryl-, heteryl)yliden)amino-1,2,4-triazole-3-thiols have been synthesized, their structure and individuality has been confirmed by complex of modern physical-chemical methods of analysis. In all cases, the values of the investigated physical-chemical constants coincide with the calculated ones.

What happanes when a large dose of magnesium sulphate is infused intravenously?

Introduction: During hospital admission, various drugs are prescribed. Most of these medications are high-alert medications, which can cause significant damage to the patient’s body due to its unintentional usage. Unfamiliarity with safe dosage ranges, confusion between similar looking drugs, mislabeling of drugs, equipment misuse, or malfunction and communication problems could induce this kind of errors. We want to report a case of accidental injection of a high dose of magnesium sulfate (MgSO4) in a girl with diabetes mellitus (DM). Case Report: A 17-year-old girl was admitted to the internal ward for close observation of poorly control DM with complication of hypoglycemia. The patient had muscle weakness and loss of deep tendon reflexes (DTRs) and severe constipation hypoventilation following the accidental infusion of 20 mg of magnesium sulfate (MgSO4). But, the patient was lucky to survive with medical treatment. Conclusion: MgSO4 is among one of the most frequently used drugs in medical practice. However, despite years of use and provider familiarity, the prescription of MgSO4 occasionally results in accidental overdose and patient damage.

Ethanolic leaf extract of <i>Langenaria breviflora</i> (bitter gourd) inhibits gastric onslaught in indomethacininduced ulcerated rats

Objective : Gastrointestinal toxicity remains a barrier to applications of non-steroidal anti-inflammatory drugs in medical practice. Plant extract with excellent therapeutic potential may proffer solution to this menace. This study investigated the gastroprotective effect of Lagenaria breviflora leaves extract against indomethacinmediated gastric ulcer in rats. Methodology and result : Ulceration in the rat was induced by a single oral dose of indomethacin (60 mg/kg body weight). Ulcerated rats were orally administered with Lagenaria breviflora extract at 200 mg/kg body weight once daily for 21 days prior to and after ulcer induction. Gastric secretions and antioxidant parameters were then evaluated. The study indicates that indomethacin caused a significant increase in ulcer index, gastric acidity, malondialadehyde level and pepsin activity. Administration of Lagenaria breviflora in rats reversed these metabolic alterations. The extract also attenuated the reduced activity of catalase, pH and mucin content in the ulcerated rats. Conclusions and application of findings : These findings are indicative of gastroprotective and antioxidative attributes of the extract, which is revealed in the percentage protection offered against ulceration. The supportive evidences in this study suggest that the effect of leaves extract of Lagenaria breviflora proved to be capable of modulating indomethacin-mediated gastric ulceration and could be harnessed as preventive therapy in the treatment of gastric ulcer related disorder. Key words : Gastroprotective; H 2 receptor; Medicinal; NSAIDS; Proton pump inhibitor; Ulceration.

Thermostable alkaline β-lactamase isolation and purification from thermophilic bacterial strainGeobacillus stearothermophilus“AAP7919”

β-Lactam antibiotic resistance has been a big problem since the usage of these antibiotic drugs in medical practice. For reducing the side-effects of these antibiotics, the β-lactam antibiotic degrading enzymes play a major role. A thermophilic bacterial strain Geobacillus stearothermophilus “AAP7919” (NCBI accession number GU459259) isolated from oil sludge site, was found capable of producing of β-lactamase enzyme in alkaline condition (pH 10) with Benzyl-penicillin as substrate. In the present study an attempt was made to characterize and optimize the production of this enzyme by ion exchange chromatographic purification followed by SDS - PAGE and FTIR studies. Primarily the enzyme activities of extracellular and intracellular β-lactamase were detected as 33.15 U mg−1 and 15.56 U mg−1 respectively. The optimal production of β-lactamase was determined at pH 10.0 (828.73 U mg−1) at 40°C temperature and the maximum thermal stability period with enzyme activity 563.54 U mg−1 was observed at 210 min (50°C). The main functional groups which are involved in IR adsorption process were found to be alcohols, alkenes and alkyl halides. The broad intense absorption peaks at 3436 cm−1 indicated the existence of alcohol groups. The peaks located at 1135 cm−1, 1054 cm−1 and 711 cm−1 were characteristics of alkyl halide groups. The peaks located at 1633 cm−1, 997 cm−1 and 923 cm−1 were characteristics of alkenes groups. The peaks at 2083 cm and 1405 cm were characteristics of alkynes and aromatic groups respectively

Practice Audit in Gastroenterology – the Route to Improving Quality and Safety

Practice audits provide insight into quality of clinical care and may drive improvement (1). Increasingly, such practice audits are driven not only by individual physicians but by peer groups and national specialist societies. In gastroenterology and hepatology, several areas of procedural practice provide excellent opportunities for peer-comparator practice audit such as colonoscopy, gastrointestinal bleeding, endoscopic retrograde cholangiopancreatography, endoscopic ultrasound fine-needle aspiration, liver biopsy and detection of Barrett’s esophagus. In addition, nonprocedural practice in gastroenterology such as inflammatory bowel disease and management of chronic diarrhea, dysphagia, viral hepatitis and dyspepsia offer some of the areas of practice that will benefit from peer-comparator practice audits. Increasingly, both personal benchmarking and unit-based benchmarking are becoming equally important to ensuring delivery of high-quality care. This will strive to avoid unwarranted variation in practice through insight, education and training. Colonoscopy practice is leading the development of quality assurance in gastroenterology, being driven by colorectal cancer screening in the asymptomatic population. In the present issue of The Canadian Journal of Gastroenterology, Armstrong et al (2) (pages 13–20) report the finding of the Canadian Association of Gastroenterology (CAG) colonoscopy audit. The data were uniquely collected electronically in real time. While the mean cecal intubation rate was 95%, it was worrying that 42% of colonoscopists reported a mean withdrawal time of less than 6 min. Ten per cent of participants had a mean cecal intubation rate of less than 85%. Other factors that may affect polyp detection such as proper positioning of patients during withdrawal and scrupulous cleaning of the colon by water spray were not reported in this audit. Ten per cent of participants reported polypectomies in 13% or less of their colonoscopies. The linking of processes such as colonoscope withdrawal time to outcome and polyp detection rate provides a strong validation of such a practice audit. The findings may help focus training programs on improving withdrawal time and polyp detection rates by raising awareness in colonoscopists. The outcome of such improvement will be more effective colon cancer screening programs for the population. An important aspect of colonoscopy practice is the knowledge of guidelines such as the most appropriate interval for follow-up colonoscopy after polyp removal or the recognition of the emerging importance of serrated polyps (3). These impact on quality of practice and resource use, and should, therefore, be regulated as closely as the use of drugs in medical practice. Individual variation in practice should be minimized and monitored in areas of practice underpinned by evidence-based national guidelines such as the recently published CAG guidelines (4). Surveillance colonoscopy continues to be underused in high-risk patients and overused in average-risk patients (5). In the face of mounting wait times for colonoscopy, appropriate allocation of this scarce resource is pivotal to favourably affecting outcome. Gastroenterology training programs must focus on quality of endoscopy training using validated benchmarks, but continuing peer-comparator audits are essential in maintaining and improving quality – it is important that such processes are inclusive of all practicing endoscopists both in academic and community settings. The Canadian Journal of Gastroenterology is striving to focus on quality assurance and safety as key areas of research and audit. These are also important national roles for the CAG and the Canadian Association for the Study of the Liver. The structural requirements necessary for quality improvement are best underpinned by national specialist organizations (Figure 1). The public requires continuous demonstration of development, maintenance and measurement of professional competencies by gastroenterologists in an ongoing, structured manner. Increasingly, the government, as payer, will demand evidence of high-quality practice before investing their resources in health care. The Journal has already published several articles on colonoscopy training and quality improvement. Quality assurance in colonoscopy is serving as a model for developing quality assurance programs more widely in gastroenterology and hepatology. Medical quality assurance will be an area of research and development that will characterize the Journal and provide it with a distinctive feature. The appointment of a specialist editor in quality assurance indicates the commitment of the Journal to publishing high-quality articles in this area as a pivotal theme. Figure 1 Elements of peer-comparator quality assurance programs

Hydroxychloroquine-induced hyperpigmentation: a case report

The antimalarials are one of the most commonly prescribed drugs in medical practice, for conditions such as rheumatoid arthritis as well as malaria. They are generally well-tolerated and the possible side effects of synthetic antimalarials, though infrequent, are well known. Besides the familiar adverse reactions, a localized mucocutaneous bluish-grey to black discolouration can sometimes be seen with antimalarial drugs. The aim of this report was to draw attention to the localized mucocutaneous bluish-grey hyperpigmentation induced by hydroxychloroquine with a case presentation and a review of the literature.

Biomarker as a classifier in pharmacogenomics clinical trials: a tribute to 30th anniversary of PSI

Pharmacogenetics is one of many evolving sciences that have come to the fore since the formation of the Statisticians in the Pharmaceutical Industry (PSI) 30 years ago. Following the completion of the human genome project and the HapMap in the early 21st century, pharmacogenetics has gradually focused on studies of whole-genome single-nucleotide-polymorphisms screening associating disease pathophysiology with potential therapeutic interventions. Around this time, transcription profiling aiming at similar objectives has also been actively pursued, known as pharmacogenomics. It has become increasingly apparent that treatment effects between different genomic patient subsets can be dissimilar, and the value and need for genomic biomarkers to help predict effects, particularly in cancer clinical studies, have become issues of paramount importance. Pharmacogenomics/pharmacogenetics has thus become intensely focused on the search for genomic biomarkers for use as classifiers to select patients in randomized-controlled trials.We highlight that the predictive utility of a genomic classifier has tremendous clinical appeal and that there will be growing examples in which use of a companion diagnostic will need to be considered and may become an integral part in the utilization of drugs in medical practice. The credible mechanism to test the clinical utility of a genomic classifier is to employ the study results from a prospective trial that recruits all patients. Such investigations, if well designed, will allow analysis of all relevant performance factors in the drug and diagnostic combination including the sensitivity, specificity, positive and negative predictive values of the diagnostic test and the efficacy of the drug.

Recycling of drugs in medical practice

Recycling of drugs in medical practice