Statin-Induced Myopathy

Scientific relevance. Being the main class of medicinal products for dyslipidaemia treatment, statins are widely used in clinical practice in various patient populations. However, statins can cause statin-associated muscle symptoms (SAMS), which are the most frequent and, in some cases, even life-threatening adverse reactions associated with these medicinal products.Aim. The study aimed to perform a systematic review of the epidemiology, classification, and physiological pathogenesis of SAMS, risk factors for this complication, and clinical guidelines for primary care physicians regarding the identification and treatment of patients with SAMS.Discussion. SAMS is an umbrella term that covers various forms of myopathies associated with satin therapy. According to the published literature, the prevalence of SAMS varies considerably and may depend on the study design, inclusion criteria, and the medicinal product used. SAMS has multiple putative pathogenic pathways that include genetically determined processes, abnormalities in mitochondrial function, defects in intracellular signalling and metabolic pathways, and immune-mediated reactions. The main known risk factors for developing SAMS include high-dose statins, drug–drug interactions, genetic polymorphisms, female sex, older age, Asian race, history of kidney, liver, and muscle disease, and strenuous physical activity. Given the lack of universally recognised algorithms for diagnosing SAMS, clinicians should consider the clinical presentation and the temporal relationship between statin therapy and symptoms. Other factors to consider include changes in muscle-specific enzyme levels and, in some cases, the results of blood tests for antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.Conclusions. To ensure the safety of statin therapy, it is essential to raise clinicians’ awareness of the risk factors for SAMS, indicative clinical and laboratory findings, and the need for dynamic patient monitoring, including the involvement of clinical pharmacologists

Drug-Induced Acute Kidney Injury

Drug-induced nephrotoxicity is the third most common cause of acute kidney injury (AKI). The aim of the study was to analyse and summarise data on the factors and mechanisms responsible for increased risk of drug-induced AKI, to analyse potential methods of its prevention and treatment. At present, the following phenotypes of drug-induced AKI are distinguished: acute vascular disease, acute glomerular disease, acute tubular injury / necrosis, and acute interstitial nephritis. It was discovered that most often these complications occur following the use of antimicrobial drugs, renin-angiotensin-aldosterone system inhibitors, non-steroidal anti-inflammatory drugs, and anticancer drugs, including targeted therapy. Risk factors for drug-induced AKI include age >65, female gender, low body weight, pre-existing chronic kidney disease, hypovolemia, hypoalbuminemia, acute and chronic heart failure, diabetes, malignancies, liver cirrhosis, prolonged use of nephrotoxic drugs, and simultaneous use of two or more nephrotoxic drugs. Discontinuation of the drug which resulted in kidney failure is the first and foremost principle for managing not only drug-induced, but all AKI patients. The use of potentially nephrotoxic drugs should be avoided, especially in high-risk patients, in order to prevent drug-induced AKI. If a patient needs a drug that affects renal hemodynamics, the therapy should begin with a minimum effective dose, and combinations of two and more nephrotoxic drugs should be avoided. Close monitoring of kidney function is crucial for high-risk patients. They should also be informed about the importance of adequate water consumption schedule for prevention of hypovolemia

Intergenerational effects of ionizing radiation: review of recent studies from human data (2018–2021)

Purpose: The purpose of this paper was to conduct a review of the studies published between 2018 and 2022 to investigate radiation-related effects in the offspring of human individuals exposed to ionizing radiation. Methods: The search identified 807 publications, from which 9 studies were selected for detailed analysis to examine for effects in children whose parents were exposed to various types and doses of radiation. Results: The review does not yield substantial evidence supporting intergenerational effects of radiation exposure in humans. However, caution is required when interpreting the results due to limitations in the majority of the published articles. Conclusion: This review, covering the period 2018–2022, serves as an extension of the previous systematic review conducted by Stephens et al. (Citation2024), which encompassed the years 1988–2018. Together, these two papers offer a comprehensive overview of the available evidence regarding the intergenerational effects of parental pre-conceptional exposure to ionizing radiation. Overall, the findings do not provide strong evidence supporting a significant association between adverse (or other) outcomes in unexposed children and parental preconception radiation exposure.The author(s) reported there is no funding associated with the work featured in this article

A Statistical Test of Heterogeneous Subgraph Densities to Assess Clusterability

Determining if a graph displays a clustered structure prior to subjecting it to any cluster detection technique has recently gained attention in the literature. Attempts to group graph vertices into clusters when a graph does not have a clustered structure is not only a waste of time; it will also lead to misleading conclusions. To address this problem, we introduce a novel statistical test, the-test, which is based on comparisons of local and global densities. Our goal is to assess whether a given graph meets the necessary conditions to be meaningfully summarized by clusters of vertices. We empirically explore our test’s behavior under a number of graph structures. We also compare it to other recently published tests. From a theoretical standpoint, our test is more general, versatile and transparent than recently published competing techniques. It is based on the examination of intuitive quantities, applies equally to weighted and unweighted graphs and allows comparisons across graphs. More importantly, it does not rely on any distributional assumptions, other than the universally accepted definition of a clustered graph. Empirically, our test is shown to be more responsive to graph structure than other competing tests

Impact of uncertainties in exposure assessment on estimates of thyroid cancer risk among Ukrainian children and adolescents exposed from the chernobyl accident

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy-1 (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy-1 (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy-1 (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p= 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment

Drug-Induced Atrial Fibrillation / Atrial Flutter

Drug-induced atrial fibrillation / flutter (DIAF) is a serious and potentially life-threatening complication of pharmacotherapy. Purpose of the work: systematization and analysis of scientific literature data on drugs, the use of which can cause the development of DIAF, as well as on epidemiology, pathophysiological mechanisms, risk factors, clinical picture, diagnosis and differential diagnosis, treatment and prevention of DIAF. Analysis of the literature has shown that many groups of drugs can cause the development of DIAF, with a greater frequency while taking anticancer drugs, drugs for the treatment of the cardiovascular, bronchopulmonary and central nervous systems. The mechanisms and main risk factors for the development of DIAF have not been finally established and are known only for certain drugs, therefore, this section requires further study. The main symptoms of DIAF are due to the severity of tachycardia and their influence on the parameters of central hemodynamics. For diagnosis, it is necessary to conduct an electrocardiogram (ECG) and Holter monitoring of an ECG and echocardiography. Differential diagnosis should be made with AF, which may be caused by other causes, as well as other rhythm and conduction disturbances. Successful treatment of DIAF is based on the principle of rapid recognition and immediate discontinuation of drugs (if possible), the use of which potentially caused the development of adverse drug reactions (ADR). The choice of management strategy: heart rate control or rhythm control, as well as the method of achievement (medication or non-medication), depends on the specific clinical situation. For the prevention of DIAF, it is necessary to instruct patients about possible symptoms and recommend self-monitoring of the pulse. It is important for practitioners to be wary of the risk of DIAF due to the variety of drugs that can potentially cause this ADR

Лекарственно-индуцированные поражения легких противоопухолевыми препаратами: распространенность, некоторые препараты и механизмы их воздействия. Часть 2

The article analyzes 49 publications on adverse drug reactions occurring during therapy with antitumor drugs. It presents data on pneumotoxicity and its clinical manifestations for such anticancer drugs as bleomycin, busulfan, cyclophosphamide, chlorambucil, methotrexate, nitrosourea derivatives, and taxanes, while the mechanisms of lung injury are not entirely clear and require further research. The prevention of drug-induced lung injury requires raising awareness among practicing physicians of different specialties, primarily general practitioners, rheumatologists, clinical immunologists, pulmonologists, phthisiologists, and oncologists due to non-specific manifestations of drug-induced lung injury and the use of antitumor drugs for other diseases apart from cancer.Проанализировано 49 источников литературы о нежелательных лекарственных реакциях, возникающих при терапии противоопухолевыми препаратами. Представлены данные о пневмотоксичности и ее клинических проявлениях для таких противоопухолевых препаратов, как блеомицин, бусульфан, циклофосфамид, хлорамбуцил, метотрексат, производные нитрозомочевины, таксаны, при этом механизмы развития поражения легких не совсем ясны, что требует дальнейших исследований. Для профилактики лекарственно-индуцированного поражения легких необходима информированность практикующих врачей разных специальностей, прежде всего терапевтов, ревматологов, клинических иммунологов, пульмонологов, фтизиатров, онкологов, ввиду неспецифичности симптомов лекарственно-индуцированного поражения легких и применения противоопухолевых лекарственных средств не только при развитии онкологических заболеваний

Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956–2004

In the 1950s, the Mayak nuclear weapons facility in Russia discharged liquid radioactive wastes into the Techa River causing exposure of riverside residents to protracted low-to-moderate doses of radiation. Almost 10 000 women received estimated doses to the stomach of up to 0.47 Gray (Gy) (mean dose=0.04 Gy) from external γ-exposure and 137Cs incorporation. We have been following this population for cancer incidence and mortality and as in the general Russian population, we found a significant temporal trend of breast cancer incidence. A significant linear radiation dose–response relationship was observed (P=0.01) with an estimated excess relative risk per Gray (ERR/Gy) of 5.00 (95% confidence interval (CI), 0.80, 12.76). We estimated that approximately 12% of the 109 observed cases could be attributed to radiation

The influence of antyhypertensive therapy of valsartan and fixed combination with hydrochlorothiazide use on pulse-wave velocity and central arterial pressure in patients with arterial hypertension of 1-2 grades in international VICTORY clinical trial

Objective - to explore influence of valsartan monotherapy use and its use in combination with hydrochlorothiazide (HCTZ) on pulse-wave velocity (PWV) and central arterial pressure (CAP) in patients with arterial hypertension (AH) of 1-2 grades in international VICTORY clinical trial. Materials and methods. The international multicenter prospective randomized clinical study VICTORY that lasted for 16 weeks included patients with 1-2 grades AH. In patients who previously received antihypertensive therapy a 7 days washout period was carried out. All patients started their therapy with 80 mg valsartan (Valsacor®, KRKA, Slovenia); in Russia the starter dose of Valsacor®, KRKA was 160 mg in previously treated patients that did not influence the study results. If after 4 weeks of treatment BP was more than 140/90 mm hg (more than 130/80 mm hg in high risk patients or in diabetes mellitus patients) the dose of valsartan was increased to 160 mg (320 mg in Russia) or diuretic in fixed combination with valsartan was added (160 mg valsartan/12.5 mg HCTZ): Valsacor® H 160 (KRKA, Slovenia). If target BP after 8 weeks of treatment was not reached valsartan dose was increased to 320 mg or fixed combination of valsartan and diuretic (160 mg/12.5 mg) was used. If target BP after 12 weeks of treatment was not reached - valsartan and diuretic 320 mg/12.5 mg were used. PWV and CAP (SphygmoCor®, AtCorMedical) were assessed at baseline and after 16 weeks of treatment. The primary endpoints were assessment of the impact of studied medications on aortic stiffness, aortic augmentation index and comparison of absolute medians of reached central and peripheral BP reduction with baseline value. Results. Of 365 patients included in the study 74 were included in PWV and CAP study subgroup. Valsartan and its combination with HCTZ were effective in CBP reduction. The mean absolute reduction of central systolic and diastolic BP after 16 weeks of treatment was 19.7±12.9 mm hg and 13.9±8.5 mm hg, respectively (