Optimal Drug Treatment Research Articles

Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 has spread in many countries, replacing the earlier Omicron subvariant BA.1 and other variants. Here, using a cell culture infection assay, we quantified the intrinsic sensitivity of BA.2 and BA.1 compared with other variants of concern, Alpha, Gamma, and Delta, to five approved-neutralizing antibodies and antiviral drugs. Our assay revealed the diverse sensitivities of these variants to antibodies, including the loss of response of both BA.1 and BA.2 to casirivimab and of BA.1 to imdevimab. In contrast, EIDD-1931 and nirmatrelvir showed a more conserved activities to these variants. The viral response profile combined with mathematical analysis estimated differences in antiviral effects among variants in the clinical concentrations. These analyses provide essential evidence that gives insight into variant emergence's impact on choosing optimal drug treatment.

Modulation of sensory cortical activity by deep brain stimulation in advanced Parkinson's disease.

Despite optimal oral drug treatment, about 90% of patients with Parkinson's disease develop motor fluctuation and dyskinesia within 5–10 years from the diagnosis. Moreover, the patients show non‐motor symptoms in different sensory domains. Bilateral deep brain stimulation (DBS) applied to the subthalamic nucleus is considered the most effective treatment in advanced Parkinson's disease, and it has been suggested to affect sensorimotor modulation and relate to motor improvement in patients. However, observations on the relationship between sensorimotor activity and clinical improvement have remained sparse. Here, we studied the somatosensory evoked magnetic fields in 13 right‐handed patients with advanced Parkinson's disease before and 7 months after stimulator implantation. Somatosensory processing was addressed with magnetoencephalography during alternated median nerve stimulation at both wrists. The strengths and the latencies of the ~60‐ms responses at the contralateral primary somatosensory cortices were highly variable but detectable and reliably localized in all patients. The response strengths did not differ between preoperative and postoperative DBSON measurements. The change in the response strength between preoperative and postoperative condition in the dominant left hemisphere of our right‐handed patients correlated with the alleviation of their motor symptoms (p = .04). However, the result did not survive correction for multiple comparisons. Magnetoencephalography appears an effective tool to explore non‐motor effects in patients with Parkinson's disease, and it may help in understanding the neurophysiological basis of DBS. However, the high interindividual variability in the somatosensory responses and poor tolerability of DBSOFF condition warrants larger patient groups and measurements also in non‐medicated patients.

The relationship between cost and the recommendation, refusal, and discontinuation of treatment for chronic myeloid leukemia and multiple myeloma in Japan: a cross-sectional exploratory survey

Aims This study aimed to ascertain the number of patients with chronic myelogenous leukemia (CML) and transplant-ineligible patients with multiple myeloma (MM) not recommended by their physicians for optimal drug treatment or who refuse, discontinue, reduce, or skip treatment owing to cost in Japan. Methods A cross-sectional survey was conducted among hematologists, hematologic oncologists, and oncologists in Japan treating ≥1 patient with CML or ≥5 transplant-ineligible patients with MM per year. Results A total of 212 physicians participated: 105 treating patients with CML and 107 treating transplant-ineligible patients with MM. While treatment cost did not lead to non-optimal treatment most patients, physicians reported that they recommended non-optimal treatment to 6.53% of their patients with CML and 1.41% of their transplant-ineligible patients with MM, that 1.51 and 0.35% of their patients, respectively, refused treatment and that 1.97 and 0.71% discontinued treatment owing to treatment cost. However, no significant differences in the effect of treatment cost on recommendation, discontinuation, refusal, or reduction of treatment were observed. Non-recommendation of optimal treatment owing to treatment cost was most common for third-line CML and fourth-line transplant-ineligible MM treatment. Discontinuation due to treatment cost was most common in third-line treatment for both. Conclusion Our results show that non-optimal treatment due to treatment cost occurs among some physicians in Japan for patients with CML and transplant-ineligible patients with MM, but it may be limited to a small percentage of patients. Further research is needed to identify the drivers of treatment decisions for physicians and patients, including those involving treatment cost.

Cost-benefit analysis of new lipid-lowering agents

Patients with atherosclerotic cardiovascular disease have ahigh risk for subsequent cardiovascular events despite optimal drug treatment including statins and ezetimibe. Dyslipidemia represents acentral and direct cause of this, with afrequent failure to achieve the target values recommended in the guidelines. New lipid-lowering substances are increasingly becoming available for treatment of this residual risk. Due to their high cost, cost-effectiveness analyses are required in order to justify their use. Important variables when considering the cost-effectiveness of adrug are quality adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). The lower bounds of the ICER determining the cost-effectiveness of atreatment vary between healthcare systems. The proprotein convertase subtilisin-kexin type9 (PCSK9) inhibitors alirocumab and evolocumab are deemed to be cost-effective particularly in patients with high levels of low-density lipoprotein cholesterol (LDL-C) prior to treatment or with ahigh cardiovascular risk as determined by the presence of defined risk criteria. Similar considerations apply to the PCSK9 small interfering RNA (siRNA) inclisiran. Administration of bempedoic acid is deemed cost-effective especially in patients with statin intolerance. Eicosapentaenoic acid is deemed cost-effective overall, although the data with respect to the exact placebo-controlled efficacy are still inconclusive.

Evaluating the efficacy and safety of percutaneous coronary intervention (PCI) versus the optimal drug therapy (ODT) for stable coronary heart disease: a systematic review and meta-analysis.

BackgroundMany studies have reported potential benefits of percutaneous coronary intervention (PCI) versus optimal drug therapy (ODT) for patients with stable coronary heart disease but with inconsistent results. To examine this, an explicit systematic review and meta-analysis was conducted to compared the clinical outcomes of PCI and ODT in these patients.MethodsThe following terms were combined to search relative articles through databases PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science published from January 2010 to November 2021 according to Participants, Intervention, Control, Outcomes, Study (PICOS) criteria: “coronary heart disease”, “stable coronary heart disease”, “stable angina pectoris”, “percutaneous coronary intervention”, “PCI”, “percutaneous transluminal coronary angioplasty”, “drug therapy”, “optimized drug treatment”, and “optimized drug therapy”. The meta-analysis was performed by RevMan 5.2, and the Cochrane risk of bias tool was used to evaluate the quality of the included studies.ResultsA total of 12 articles were included in the final analysis. There were 4,288 cases of PCI patients and 4,261 cases of ODT patients. The results showed that, when comparing PCI with ODT, there was a significant difference in the probability of myocardial infarction [relative risk (RR) =0.63; 95% confidence intervals (CI): 0.45–0.90] and the patient mortality (RR =0.51; 95% CI: 0.40–0.64). However, there was no significant difference in the prevalence of stroke (RR =1.33; 95% CI: 0.82–2.17), revascularization (RR =0.86; 95% CI: 0.46–1.62) and patient quality of life (MD =10.44; 95% CI: −1.84 to 22.73). Performance bias and detection bias were all unclear in the included studies and should be warned.DiscussionCompared with ODT, PCI reduced the mortality and myocardial infarction rate of patients with CTO or severe coronary artery stenosis. However, the incidence of stroke, revascularization, and quality of life of patients were not significant different between PCI and ODT. Performance bias and detection bias should be cautioned.

Device and surgical treatment of patients with heart failure based on the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Management of all patients with heart failure and reduced left ventricular ejection fraction is based on optimal drug treatment - „the great four” that reduce mortality (1-angiotensin converting enzyme inhibitors or angiotensin receptor neprilyzine inhibitor; 2-beta-adrenoblockers; 3-mineralocorticoid receptor antagonists; 4-sodium-glucose cotransporter inhibitors-2). For certain categories of patients, treatments with implantable cardiac devices (CRT-P/D or ICD) and cardiac surgery (coronary artery bypass grafting, aortic or mitral valve repair operations) that improve the life prognosis are required, and for advanced heart failure may be considered methods of mechanical circulatory support and heart transplantation.

Real life experience with the wearable cardioverter-defibrillator in an international multicenter Registry

Patients at high risk for sudden cardiac death (SCD) may benefit from wearable cardioverter defibrillators (WCD) by avoiding immediate implantable cardioverter defibrillator (ICD) implantation. Different factors play an important role including patient selection, compliance and optimal drug treatment. We aimed to present real world data from 4 centers from Germany and Switzerland. Between 04/2012 and 03/2019, 708 patients were included in this registry. Patients were followed up over a mean time of 28 ± 35.5 months. Outcome data including gender differences and different etiologies of cardiomyopathy were analyzed. Out of 708 patients (81.8% males, mean age 61.0 ± 14.6), 44.6% of patients had non-ischemic cardiomyopathy, 39.8% ischemic cardiomyopathy, 7.9% myocarditis, 5.4% prior need for ICD explantation and 2.1% channelopathy. The mean wear time of WCD was 21.2 ± 4.3 h per day. In 46% of patients, left ventricular ejection fraction (LVEF) was > 35% during follow-up. The younger the patient was, the higher the LVEF and the lower the wear hours per day were. The total shock rate during follow-up was 2.7%. Whereas an appropriate WCD shock was documented in 16 patients (2.2%), 3 patients received an inappropriate ICD shock (0.5%). During follow-up, implantation of a cardiac implantable electronic device was carried out in 34.5% of patients. When comparing German patients (n = 516) to Swiss patients (n = 192), Swiss patients presented with longer wear days (70.72 ± 49.47 days versus 58.06 ± 40.45 days; p = 0.001) and a higher ICD implantation rate compared to German patients (48.4% versus 29.3%; p = 0.001), although LVEF at follow-up was similar between both groups. Young age is a negative independent predictor for the compliance in this large registry. The most common indication for WCD was non-ischemic cardiomyopathy followed by ischemic cardiomyopathy. The compliance rate was generally high with a decrease of wear hours per day at younger age. Slight differences were found between Swiss and German patients, which might be related to differences in mentality for ICD implantation.

Relevance of COMT inhibitors in the treatment of motor fluctuations

Catechol O‑methyltransferase (COMT) inhibitors have been established in the treatment of Parkinson's disease for more than 20years. They are considered the medication of choice for treating motor fluctuations. The available COMT inhibitors, entacapone, opicapone and tolcapone, differ pharmacokinetically in terms of their half-lives with implications for the dose frequency, in their indication requirements and in their spectrum of side effects, including diarrhea and yellow discoloration of urine. Many patients with motor fluctuations are currently not treated with COMT inhibitors and are, therefore, unlikely to receive individually optimized drug treatment. This manuscript summarizes the results of aworking group including several Parkinson's disease experts, in which the value of COMT inhibitors was critically discussed.

Fatal pulmonary tumour thrombotic microangiopathy in patient with ovarian adenocarcinoma: review and a case report

BackgroundPulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease in which tumour cells embolize to the pulmonary vasculature leading to pulmonary hypertension and right heart failure. Early diagnosis is essential for timely treatment which can reduce intimal pulmonary vascular proliferation and prolong survival, improve the symptoms. Due to rare occurrences and no clear diagnostic guidelines the disorder usually is found post-mortem. We present a review of this rare disease and a case of post-mortem diagnosed pulmonary tumour thrombotic microangiopathy in a young female.Case presentation51 years old woman presented with progressively worsening dyspnea, right ventricular failure signs and symptoms. Computerized tomography denied pulmonary embolism. 2D transthoracic echocardiography demonstrated right ventricle dilatation and dysfunction, severely increased systolic pulmonary pressure. Right heart catheterization revealed pre-capillary pulmonary hypertension with mean pulmonary artery pressure of 78 mmHg, pulmonary wedge pressure of 15 mmHg, reduced cardiac output to 1.78 L/min with a calculated pulmonary vascular resistance of 35 Wood units, and extremely low oxygen saturation (26%) in pulmonary artery. Because of worsening ascites, pelvic magnetic resonance imaging was performed, tumours in both ovaries were diagnosed. Due to the high operative risk, detailed tumour diagnosis surgically was not established. The patient developed progressive cardiorespiratory failure, unresponsive to optimal heart failure drug treatment. A postmortem morphology analyses revealed tumorous masses in pre-capillary lung vessels, right ventricle hypertrophy, ovary adenocarcinoma.ConclusionsAn early diagnosis of PTTM is essential. Most cases are lethal due to respiratory failure progressing rapidly. Patients with a history of malignancy, symptoms and signs implying of PH should be considered of having PTTM. If detected early enough, combination of chemotherapy with specific PH therapy is believed to be beneficial in reducing intimal proliferation and prolonging survival, along with improving the symptoms.

Precision Medicine in Diabetes.

Tailoring treatment or management to groups of individuals based on specific clinical, molecular, and genomic features is the concept of precision medicine. Diabetes is highly heterogenous with respect to clinical manifestations, disease progression, development of complications, and drug response. The current practice for drug treatment is largely based on evidence from clinical trials that report average effects. However, around half of patients with type 2 diabetes do not achieve glycaemic targets despite having a high level of adherence and there are substantial differences in the incidence of adverse outcomes. Therefore, there is a need to identify predictive markers that can inform differential drug responses at the point of prescribing. Recent advances in molecular genetics and increased availability of real-world and randomised trial data have started to increase our understanding of disease heterogeneity and its impact on potential treatments for specific groups. Leveraging information from simple clinical features (age, sex, BMI, ethnicity, and co-prescribed medications) and genomic markers has a potential to identify sub-groups who are likely to benefit from a given drug with minimal adverse effects. In this chapter, we will discuss the state of current evidence in the discovery of clinical and genetic markers that have the potential to optimise drug treatment in type 2 diabetes.

The effectiveness of acromegaly treatment according to the Registry of patients with pituitary tumors in the Republic of Tatarstan

Background: Acromegaly is a severe progressive neuroendocrine disease caused by chronic elevated concentrations of growth hormone and insulin-like growth factor 1 in individuals with completed physiological growth and leading to early disability and mortality. The Acromegaly Registry with its regular updates makes it possible to merge and systematize all the available information on the diseases, to assess the efficacy of treatment algorithms and to choose an optimal diagnostic and treatment strategy in a given territory.Aim: To evaluate the efficacy of various treatments for acromegaly based on the analysis of the regional Registry of patients with pituitary tumors in the Republic of Tatarstan.Materials and methods: The study was based on data from 217 patients with somatotropin producing pituitary adenomas entered in the Registry of patients with pituitary tumors in the Republic of Tatarstan as per January 2021. One hundred and eighty one (181 patients) with sufficient data to assess the remission rates and the disease course were included into the analysis.Results: Endonasal endoscopic adenomectomy as a first-line treatment has been performed in 93% (169/181) of the patients, with 34% of the cases (57/169) being in the full postoperative remission. The efficacy of surgical treatment depended on the tumor size, invasion grade and aggressiveness. A 1st generation long-acting somatostatin analog (octreotide) has been prescribed to 50% (91/181) of the patients (11 patients as first-line therapy and 80 patients after adenomectomy), with biochemical remission rate of 56% (51/91). Radiological treatment has been completed in 11,6% (21/181) of the patients. The complete remission rate after all treatment modalities (surgical, medical, and radiation therapy) was 60% (108/181).Conclusion: The effectiveness of treatment for acromegaly in the Republic of Tatarstan is comparable to that in the all-Russian and international registries. Nevertheless, 40% of the patients with acromegaly in the region do not have their disease biochemically controlled indicating the need to optimize drug treatment.

Molecular-Genetic Portrait of Breast Cancer with Triple Negative Phenotype.

Simple SummaryBreast cancer is a genetically heterogeneous disease with different molecular biological and clinical characteristics. The available knowledge about the genetic heterogeneity of the most aggressive molecular subtype of breast cancer—triple-negative—has led to discoveries in drug treatment. Identification of the molecular-genetic phenotype of breast cancer is an important prognostic factor of the disease and allows personalization of the patient’s treatment.Understanding of the genetic mechanisms and identification of the biological markers of tumor progression that form the individual molecular phenotype of transformed cells can characterize the degree of tumor malignancy, the ability to metastasize, the hormonal sensitivity, and the effectiveness of chemotherapy, etc. Breast cancer (BC) is a genetically heterogeneous disease with different molecular biological and clinical characteristics. The available knowledge about the genetic heterogeneity of the most aggressive molecular subtype of breast cancer—triple-negative (TN)—has led to discoveries in drug treatment, including the use of DNA damaging agents (platinum and PARP inhibitors) for these tumors, as well as the use of immunotherapy. Most importantly, the ability to prescribe optimal drug treatment regimens for patients with TNBC based on knowledge of the molecular-genetic characteristics of this subtype of BC will allow the achievement of high rates of overall and disease-free survival. Thus, identification of the molecular-genetic phenotype of breast cancer is an important prognostic factor of the disease and allows personalization of the patient’s treatment.

Association macrophage subpopulation with cardiac biomarkers in patients with acute decompensated ischemic heart failure with reduced ejection fraction

Abstract Objective To determine the association macrophage subpopulation with cardiac biomarkers (interleukin (IL)-1β, IL-6, IL-10, highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), troponin I, interferon gamma (IFN-γ), plasma brain natriuretic peptide (BNP), and N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP), soluble interleukin 1 receptor-like 1 (ST2)) in patients with acute decompensated ischemic heart failure with reduced ejection fraction. Methods This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials.gov (#NCT02649517) and included 25 patients (84% men, LVEF of 29.17±9.4%) with ADHF. Inclusion criteria were ADHF, not earlier than 6 months after optimal surgery (PCI or/and CABG) and optimal drug treatment for ADHF according to ESC guidelines. Invasive coronary angiography was performed in all patients to exclude the progression of coronary atherosclerosis. All patients underwent endomyocardial biopsy (EMB) with immunohistochemically analysis for diagnostic myocarditis. Macrophage infiltration in the heart was assessed by double immunofluorescence. CD68 was a marker for the cells of the macrophage lineage, CD80 was considered as M1-like macrophage and CD163, CD206, stabilin-1 were as M2-like macrophage biomarkers. Each area was evaluated in 5 random fields. On admission serum levels of IL-1β, IL-6, IL-10, hsCRP, TNF-α, troponin I, IFN-γ, ST2, BNP, and NT-proBNP were measured using enzyme-linked immunosorbent assay (ELISA). The double immunofluorescence has not been performed in 4 patients. Results An association was found between CD68+/CD80+ macrophages and level of TNF-α (r=0.512, p=0.042) in all patient. After EMB, all patients were divided into 2 groups. Group 1 comprised 16 patients (64%) with myocarditis; group 2 comprised 9 patients (36%) without myocarditis. In group 1 the association was found between CD68+/CD80+ macrophages and the level of troponin I (r=0.874, p=0.05). Besides, the association was revealed CD68-/CD206+ macrophages with the level of hsCRP (r= - 0.755, p=0.03), and CD163-/CD206+ macrophages with the level of IL-6 (r=0.843, p=0,009) in group 1. CD68-/stabilin-1 macrophages were in direct correlation with level of NT-proBNP (r=0.790, p=0.02) and in inverse correlation with level of troponin I (r= - 0.711, p=0.05) in group 1. In group 2 the association was found between CD68-/CD206+ macrophages and the level of ST2 (r=0.0.537, p=0.037). Conclusion Our data suggest that many associations identified between M1-like macrophages (CD 68+/CD 80+), M2-like macrophages (CD68-/CD206+, CD163-/CD206+) and markers of inflammation (hsCRP, IL-6) and myocardial damage (NT-proBNP, troponin I) in patients with myocarditis. Whereas in patients without myocarditis, only the association of M2-like macrophages (CD68-/CD206+) with the ST2 level was revealed, probably due to the continuing unfavorable remodeling of the heart. Funding Acknowledgement Type of funding sources: None.

Improvement of Inflammation and Pain after Three Months' Exclusion Diet in Rheumatoid Arthritis Patients.

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. Methods: In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months’ dietary regimens. Results: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. Conclusions: Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.

THE ROLE OF BETA-BLOCKERS IN VETIANGINAL THERAPY IN THE CORRECTION OF VIOLATIONS OF THE AMINO ACID SPECTRUM IN PATIENTS WITH UNSTABLE ANGINA WITH CONCOMITANT DIABETES MELLITUS

The purpose of the study: to study the effect of bisoprolol and nebivolol on the spectrum of essential blood plasma AK in patients with concomitant diabetes mellitus (DM) type 2 in order to optimize drug treatment of this pathology in the future.Material and methods. The study involved 70 patients with NA with concomitant DM type 2, which was divided into two groups: group I (37 patients) as part of basic antianginal therapy received bisoprolol, group II (33 patients) received nebivolol. The control group (CG) consisted of 18 healthy individuals. All patients were tested for irreplaceable blood plasma AA by ion exchange liquid chromatography on an automatic analyzer AK T-339 produced by «Microtechna» (Czech Republic, Prague) at the Institute of Biochemistry named after OV Palladin NAMS of Ukraine. The following essential AAs were identified: arginine, valine, histidine, isoleucine, leucine, lysine, methionine, threonine, phenylalanine. Examination of patients was performed at the beginning of treatment and after 20 days. Results. It was determined that in patients with NA with concomitant DM type 2 under the influence of antianginal therapy in both groups significantly decreased the total amount of irreplaceable AA compared with control group, indicating an increase in intracellular metabolism as a compensatory response in coronary circulation. It should be noted that in patients of group II, in contrast to patients of group I, under the influence of treatment the level of histidine remained normal. The level of threonine significantly decreased compared to CG and the rate of patients in group I, the level of valine significantly increased compared to pre-treatment, the level of isoleucine significantly decreased compared with CG and with the rate of patients of group I. Importantly, ammonia levels returned to normal under the influence of basic therapy, which included nebivolol.Conclusion. The dynamics of changes in the levels of individual irreplaceable AA blood plasma, due to the mechanisms of their metabolic transformations in patients with NA with concomitant DM type 2 indicates greater effectiveness of nebivolol and the feasibility of its prescription іn complex of a basic antianginal therapy.

The clinical pharmacist’s role in enhancing the relevance of a clinical decision support system

BackgroundClinical decision support systems (CDSSs) can improve the quality of patient care by helping physicians to review their prescriptions and thus to optimize drug treatments. Nevertheless, the “alert fatigue” brought on by a large number of irrelevant alerts can decrease a CDSS’s effectiveness and thus clinical value. Involving a clinical pharmacist in the development and management of a CDSS can reduce the number of irrelevant alerts presented to physicians. Clinical pharmacists screen alerts and suggest PIs for physicians, corresponding to any proposed therapeutic change about health products, only for relevant alerts could improve the relevance and the acceptance of the information given to physicians about the risks faced by their patients. ObjectiveTo assess the value of involving clinical pharmacists in the development and maintenance of decision support rules for generating alerts and pharmaceutical interventions (PIs) and to describe the level of acceptance of these PIs by the physicians. MethodIn a retrospective, single-centre study, we evaluated the number of PIs accepted from alerts generated by the CDSS when a clinical pharmacist had developed and managed this tool. During the first 7 months of development of the CDSS, a clinical pharmacist analyzed alerts triggered by the CDSS according to its technical validity and pharmaceutical relevance. Lastly, for alerts that led to a PI, the level of acceptance by physicians was documented. ResultsDuring the study, 1430 alerts were analysed: 186 (13%) were considered to be technically invalid – mainly due to the characteristics of the interface. Of the 1244 (87.0%) technically valid alerts, 353 (24.6%) were pharmaceutically relevant and led to a PI. The three main causes of pharmaceutical irrelevance were a lack of specificity in the CDSS (70.8%), lack of relevance with regard to the ward’s habits (15.6%), and the pharmacist’s decision to recommend monitoring for the patient rather than sending a PI immediately (10.8%). 64.6% of the submitted PIs were accepted by the physicians. ConclusionThe standardized analysis of alerts by a clinical pharmacist appears to be a good way of improving the development of CDSS by limiting the generation of irrelevant alerts and the latter’s transmission to physicians. The involvement of a clinical pharmacist in the development and implementation of a CDSS appears to be novel and may help to optimize drug treatment.

A gentle introduction to understanding preclinical data for cancer pharmaco-omic modeling.

A central goal of precision oncology is to administer an optimal drug treatment to each cancer patient. A common preclinical approach to tackle this problem has been to characterize the tumors of patients at the molecular and drug response levels, and employ the resulting datasets for predictive in silico modeling (mostly using machine learning). Understanding how and why the different variants of these datasets are generated is an important component of this process. This review focuses on providing such introduction aimed at scientists with little previous exposure to this research area.

Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial

ObjectiveTo examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital.DesignCluster randomised controlled trial.Setting110 clusters of inpatient wards...

An Arm and a Leg: The Rising Cost of Cancer Drugs and Impact on Access.

Increasing cancer drug prices present global challenges to treatment access and cancer outcomes. Substantial variability exists in drug pricing across countries. In countries without universal health care, patients are responsible for treatment costs. Low- or middle-income countries are heavily impacted, with limited patient access to novel cancer treatments. Financial toxicity is seen across cancer types, countries, and health care systems. Those at highest risk include younger patients, new immigrants, visible minority groups, and those without private health coverage. Currently, cancer drug pricing does not correlate with value or clinical benefit. Value-based pricing of oncology drugs may incentivize development of higher-value medicines and eliminate excess spending on drugs that yield little benefit. Generics and biosimilars in oncology can also improve affordability and patient access, offering dramatic reductions in drug spending while maintaining patient benefit. Oncologists can promote value-based care by following evidence-based clinical guidelines that avoid low-value treatments. Researchers can also engage in value-based research that critically explores optimal cancer drug dosing, schedules, and treatment duration and defines patient populations most likely to benefit (e.g., through biomarker selection). Cancer Groundshot proposes that we improve outcomes for today's patients with cancer, including broader global access for high-value treatments, promotion of affordable cancer control strategies, and reduction of cancer morbidity and mortality through low-cost prevention and screening initiatives. Moving forward, major oncology societies recommend promoting uniform global access to essential cancer medicines and avoiding financial harm for patients as key principles in addressing the affordability of cancer drugs.

Medium-long-term results of carotid stenting in asymptomic stenosis of the carotid arteries

The article describes the experience of carotid stenting use in asymptomatic cerebral atherosclerosis. The study included 147 patients with unilateral asymptomatic carotid artery disease. The evaluation of mid-longterm results of carotid stenting in patients with asymptomatic stenosis was carried out in comparison with the use of conservative treatment in this category of patients (“optimal drug treatment”). In the course of the work, no significant intergroup difference was revealed in the incidence of adverse outcomes (TIA/stroke, death from stroke,) within a year from the moment of surgical treatment or the beginning of complex correction of risk factors.