Drug Benefit Research Articles

Construction of a Lung Adenocarcinoma Prognostic Model Utilizing Serine and Glycine Metabolism-Related Genes.

The objective of this study was to construct a prognostic model by utilizing serine/glycine metabolism-related genes (SGMGs), thus establishing a risk score for lung adenocarcinoma (LUAD). Based on the TCGA-LUAD and SGMG data set, two subtypes with different SGMG expression levels were identified by clustering analysis. Thirteen differential expression genes were used to construct RiskScore by Cox regression. GSE72094 data set was used for validation. The survival characteristics, immune features, and potential benefits of chemotherapy drugs were analyzed for two risk groups. RiskScore was constructed based on the genes ABCC12, RIC3, CYP4B1, SFTPB, CACNA2D2, IGF2BP1, NTSR1, DKK1, CREG2, PITX3, RGS20, FETUB, and IGFBP1. Patients in the low-risk (LR) group exhibited a superior overall survival. In addition, aDCs, iDSs, mast cells, neutrophils, HLA, and type II IFN were more abundant in the LR group with higher IPS scores and lower TIDE scores. In contrast, NK cells, APC coinhibition, and MHC-I were more common in the high-risk (HR) group, which may be more sensitive to chemotherapy drugs such as cisplatin, oxaliplatin, and nilotinib. RiskScore was a promising biomarker that can be used to distinguish LUAD prognosis, immune features, and sensitivity to chemotherapy drugs.

Comprehensive analysis of a tryptophan metabolism-related model in the prognostic prediction and immune status for clear cell renal carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is characterized as one of the most common types of urological cancer with high degrees of malignancy and mortality. Due to the limited effectiveness of existing traditional therapeutic methods and poor prognosis, the treatment and therapy of advanced ccRCC patients remain challenging. Tryptophan metabolism has been widely investigated because it significantly participates in the malignant traits of multiple cancers. The functions and prognostic values of tryptophan metabolism-related genes (TMR) in ccRCC remain virtually obscure.MethodsWe employed the expression levels of 40 TMR genes to identify the subtypes of ccRCC and explored the clinical characteristics, prognosis, immune features, and immunotherapy response in the subtypes. Then, a model was constructed for the prediction of prognosis based on the differentially expressed genes (DEGs) in the subtypes from the TCGA database and verified using the ICGC database. The prediction performance of this model was confirmed by the receiver operating characteristic (ROC) curves. The relationship of Risk Score with the infiltration of distinct tumor microenvironment cells, the expression profiles of immune checkpoint genes, and the treatment benefits of immunotherapy and chemotherapy drugs were also investigated.ResultsThe two subtypes revealed dramatic differences in terms of clinical characteristics, prognosis, immune features, and immunotherapy response. The constructed 6-gene-based model showed that the high Risk Score was significantly connected to poor overall survival (OS) and advanced tumor stages. Furthermore, increased expression of CYP1B1, KMO, and TDO2 was observed in ccRCC tissues at the translation levels, and an unfavorable prognosis for these patients was also found.ConclusionWe identified 2 molecular subtypes of ccRCC based on the expression of TMR genes and constructed a prognosis-related model that may be used as a powerful tool to guide the prediction of ccRCC prognosis and personalized therapy. In addition, CYP1B1, KMO, and TDO2 can be regarded as the risk prognostic genes for ccRCC.

Nonadherence to Drug Therapy among Pregnant Women in Baghdad/Al-Karkh Directorate (2022)

Abstract Objectives: This aim of the study was to estimate the prevalence of noncompliance to medication in pregnant women in Al-Karkh directorate and to address its most common causes. Methods: A cross-sectional study was conducted at a number of primary health-care centers located in Baghdad/Al-Karkh directorate including pregnant women in their second and third trimesters through a self-filled questionnaire; data were later analyzed. Results: The results obtained from the present study revealed that 185 out of 306 participants (60%) of pregnant women were noncompliant or inadequately compliant with their medication, whereas the remaining 121 (40%) were properly compliant. The most common reasons for noncompliance included wrong use of drugs (38.4%), not understanding or knowing the benefits of drugs (30.3%), forgetting to take drugs (29.7%), or thinking that they were unsafe for the fetus (25.9%). Conclusions: Appropriate health education and enhancing doctor–patient relationship and communication during antenatal care visits are crucial to achieve better compliance.

Evaluation of prescribing pattern of fixed-dose combinations in obstetrics and gynecology department of a tertiary care hospital of central India

Background: Improved patient compliance and cost effectiveness are two benefits of fixed-dose combination drugs. Irrational fixed-dose combinations (FDCs) raise the most urgent issue since they put patients at needless risk for negative medication responses. Aims and Objectives: The present study was done with objective of analyzing prescribing pattern of FDCs in department of fixed-dose combination in department of obstetrics and gynecology in a tertiary care hospital of central India. Materials and Methods: This study, which was both prospective and observational, was conducted at the tertiary care hospital of central India. This study comprised the prescriptions of all patients who visited the obstetrics and gynecology Outpatient Department during the study period. Results: In the present study, 1605 prescriptions were analyzed, comprising total 3016 drugs. Out of these 1262 were prescribed as FDCs and 1754 were prescribed as single drugs. On analyzing system-wise prescriptions, it was found that majority drugs were prescribed pertaining to gastrointestinal tract, that is, 1720 prescriptions, of which 722 (38.8%) were prescribed as FDCs. Four hundred and sixty-three drugs were prescribed related to hematological system, of which 97 (14.9%) were FDCs. Four hundred and thirty-three drugs were prescribed related to anti-infective class, comprising 196 (36.6%) FDCs. Among FDCs prescribed in gastrointestinal system, Vitamin D3 + Calcium carbonate was most commonly prescribed, accounting for 644 (51%) prescriptions. Clotrimazole + Clindamycin was most commonly prescribed FDC in anti-infective system comprising 118 (9.3%) patients. Ferrous ascorbate + folic acid was most commonly prescribed hematological FDC, accounting for 49 (3.8%) patients. Dextromethorphan + phenylephrine + Chlorpheniramine was most commonly prescribed FDC in respiratory segment accounting for 39 (2.9%) patients. Conclusion: The present study highlights a considerable number of drugs prescribed as FDCs. FDCs reduce pill burden and also help to improve patient compliance. However, rationality of FDCs should be thought before prescribing it to patients.

Cardiotoxicity detection tool for breast cancer chemotherapy: a retrospective study.

Patients with breast cancer undergoing biological therapy and/or chemotherapy perform multiple radionuclide angiography (RNA) or multigated acquisition (MUGA) scans to assess cardiotoxicity. The association between RNA imaging parameters and left ventricular (LV) ejection fraction (LVEF) remains unclear. This study aimed to extract and evaluate the association of several novel imaging biomarkers to detect changes in LVEF in patients with breast cancer undergoing chemotherapy. We developed and optimized a novel set of MATLAB routines called the "RNA Toolbox" to extract parameters from RNA images. The code was optimized using various statistical tests (e.g., ANOVA, Bland-Altman, and intraclass correlation tests). We quantitatively analyzed the images to determine the association between these parameters using regression models and receiver operating characteristic (ROC) curves. The code was reproducible and showed good agreement with validated clinical software for the parameters extracted from both packages. The regression model and ROC results were statistically significant in predicting LVEF (R2 = 0.40, P < 0.001) (AUC = 0.78). Some time-based, shape-based, and count-based parameters were significantly associated with post-chemotherapy LVEF (β = 0.09, P < 0.001), LVEF of phase image (β = 4, P = 0.030), approximate entropy (ApEn) (β = 11.6, P = 0.001), ApEn (diastolic and systolic) (β = 39, P = 0.002) and LV systole size (β = 0.03, P = 0.010). Despite the limited sample size, we observed evidence of associations between several parameters and LVEF. We believe that these parameters will be more beneficial than the current methods for patients undergoing cardiotoxic chemotherapy. Moreover, this approach can aid physicians in evaluating subclinical cardiac changes during chemotherapy, and in understanding the potential benefits of cardioprotective drugs.

Markov Decision Process Modeling in Pharmacoeconomics with Application Perspectives

Abstract Aiming at the complexity of the problems of risk prediction and drug cost and utility in pharmacoeconomics, this paper proposes the application of the Markov decision model to pharmacoeconomics, and based on this, the solution method of pharmacoeconomic optimization is proposed. After summarizing the advantages and purposes of Markov’s application in pharmacoeconomics, the Markov decision process is established from four aspects: state of the world, action, transfer, and benefit function. The Lagrangian function is constructed with the expectation of the maximum long-term drug benefit. The solution problem is converted into an unconstrained problem, and the objective solution is carried out using reinforcement learning methods. The improved algorithm’s convergence is examined. It is found that the optimized Markov decision-making algorithm obtains a cumulative payoff value of 85, which is 25 higher than that obtained by the Markov decision-making algorithm, and the Markov decision-making model is more effective in evaluating the economics of drugs or treatment measures. Evaluating the long-term benefits of therapeutic measures on cost, survival, and quality of life in sick populations has promising applications as well.

High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol.

Safety issues are detected in about one third of prescription drugs in the years following regulatory agency approval. Older adults, especially those with chronic kidney disease, are at particular risk of adverse reactions to prescription drugs. This protocol describes a new approach that may identify credible drug-safety signals more efficiently using administrative health care data. To use high-throughput computing and automation to conduct 700+ drug-safety cohort studies in older adults in Ontario, Canada. Each study will compare 74 acute (30-day) outcomes in patients who start a new prescription drug (new users) to a group of nonusers with similar baseline health characteristics. Risks will be assessed within strata of baseline kidney function. The studies will be population-based, new-user cohort studies conducted using linked administrative health care databases in Ontario, Canada (January 1, 2008, to March 1, 2020). The source population for these studies will be residents of Ontario aged 66 years or older who filled at least one outpatient prescription through the Ontario Drug Benefit (ODB) program during the study period (all residents have universal health care, and those aged 65+ have universal prescription drug coverage through the ODB). We identified 3.2 million older adults in the source population during the study period and built 700+ initial medication cohorts, each containing mutually exclusive groups of new users and nonusers. Nonusers were randomly assigned cohort entry dates that followed the same distribution of prescription start dates as new users. Eligibility criteria included a baseline estimated glomerular filtration rate (eGFR) measurement within 12 months before the cohort entry date (median time was 71 days before cohort entry in the new user group), no prior receipt of maintenance dialysis or a kidney transplant, and no prior prescriptions for drugs in the same subclass as the study drug. New users and nonusers will be balanced on ~400 baseline health characteristics using inverse probability of treatment weighting on propensity scores within 3 strata of baseline eGFR: ≥60, 45 to <60, <45 mL/min per 1.73 m2. We will compare new user and nonuser groups on 74 clinically relevant outcomes (17 composites and 57 individual outcomes) in the 30 days after cohort entry. We used a prespecified approach to identify these 74 outcomes. In each cohort, we will obtain eGFR-stratum-specific weighted risk ratios and risk differences using modified Poisson regression and binomial regression, respectively. Additive and multiplicative interaction by eGFR category will be examined. Drug-outcome associations that meet prespecified criteria (identified signals) will be further examined in additional analyses (including survival, negative-control exposure, and E-value analyses) and visualizations. The initial medication cohorts had a median of 6120 new users per cohort (interquartile range: 1469-38 839) and a median of 1 088 301 nonusers (interquartile range: 751 697-1 267 009). Medications with the largest number of new users were amoxicillin trihydrate (n = 1 000 032), cephalexin (n = 571 566), prescription acetaminophen (n = 571 563), and ciprofloxacin (n = 504,374); 19% to 29% of new users in these cohorts had an eGFR <60 mL/min per 1.73 m2. Despite our use of robust techniques to balance baseline indicators and to control for confounding by indication, residual confounding will remain a possibility. Only acute (30-day) outcomes will be examined. Our data sources do not include nonprescription (over-the-counter) drugs or drugs prescribed in hospitals and do not include outpatient prescription drug use in children or adults <65 years. This accelerated approach to conducting postmarket drug-safety studies has the potential to more efficiently detect drug-safety signals in a vulnerable population. The results of this protocol may ultimately help improve medication safety.

Demographic Insights into Migraine Prevalence and a Cost-Effective Analysis of Various Prophylactic Medications

Headache, a common human experience, has been classified since antiquity. Migraine, a prevalent disabling primary headache condition, has significant personal and societal consequences. Understanding its demography is critical for creating effective prevention and treatment methods. An observational study of 387 persons with chronic migraine was conducted over a six-month period. They were divided into three groups and given a separate prophylactic drug. Demographic information was collected at the outset, and patients were assessed at 4, 8, and 12 weeks. The study population had an average age of 38.20 ±12.78 years, with 90% of the participants being female. Migraine was most common in those under 30 (37%), followed by those between 31 and 40 (28%). The most common co-morbidity (43.5%) was anxiety. Propranolol alone was the most cost-effective preventative medication, followed by propranolol plus escitalopram. This study sheds light on the intricate relationship between migraine and demographic characteristics, underlining the significance of individualized care. Because females are more vulnerable, age-specific therapies are critical, as are gender-sensitive approaches. The potential benefits of preventative drugs in decreasing both personal and society burdens are highlighted by socioeconomic factors and cost-effectiveness analyses. To optimize outcomes and cost allocation, this study advocates for a patient-centered, comprehensive approach to migraine care. Keywords Migraine, Prevalence, Prophylactic Medications, Demographics, Cost­effectiveness Analysis

Evidence inventory: A patient-centered framework for Centers for Medicare & Medicaid Services to assess the clinical benefit of drugs to inform its maximum fair price negotiation.

The Inflation Reduction Act passed in August 2022 empowers the Centers for Medicare & Medicaid Services (CMS) to negotiate maximum fair prices for certain expensive drugs. In the process of determining maximum fair prices, CMS gathers evidence on the clinical benefits of these drugs as compared with their therapeutic alternative(s) from various sources. As patients are the primary beneficiaries of the treatment, we recommend that CMS should embrace an approach that prioritizes patient experience when evaluating such diverse sources of evidence in the assessment of the clinical benefit. Thus, we propose to draw on several existing frameworks to support the concept of "evidence inventory," a patient-centered approach to systematically evaluate benefits of drugs under consideration. This 4-step process to develop an evidence inventory includes the following: (1) Formulate the research question-in a PICO(T) (P = population, I = Intervention or exposure, C = comparator, O = outcome, and T = time frame) format, (2) Synthesize evidence, (3) Evaluate the evidence-using evidence inventory, and (4) Reevaluate evidence as new information become available. Patients and other relevant stakeholders play a critical role in each of these 4 steps. The proposed evidence inventory holds the potential to provide a structured and transparent patient-centered framework for evaluating the clinical benefits of drugs as compared with their therapeutic alternative(s) informing CMS maximum fair price negotiation.

The benefits of GLP1 receptors in cardiovascular diseases.

Glucagon like peptide-1 (GLP-1) receptor agonists are well established drugs for the treatment of type 2 diabetes (T2D). In addition to glycemic control, GLP-1 receptor agonists have beneficial other effects. They act by binding to GLP-1 receptors, which are widely distributed in the body, including cardiomyocytes and blood vessels. The aim of this article is to provide a comprehensive review of GLP-1 receptor agonists impact on cardiovascular outcomes and risk reduction. In the last decade, several cardiovascular outcomes trials (CVOT) have been conducted in order to explore cardiovascular benefit of GLP-1 receptor agonists. CVOTs primarily proved cardiovascular safety and tolerability of different GLP-1 receptor agonists, but also showed cardiovascular benefit of specific drugs. CVOTs have shown that GLP-1 receptor agonists reduce MACE in patients with T2D compared to placebo. In addition, they have positive impact on several cardiovascular risk factors such as obesity by promoting weight loss, blood pressure and blood lipid levels. Also, they stimulate the endothelium to produce nitric oxide, reduce oxidative stress, and have antiatherogenic and antiinflammatory effects. Studies have shown their positive impact on kidney outcomes in patients with T2D compared to placebo. The results of previous trials are encouraging in terms of multiple positive effects of GLP-1 receptor agonists. However, further research is needed to understand their full potential and all details of their mechanism of action, which will enable to expand the therapeutic indications and to determine their optimal use in clinical practice.

A PHARMACOECONOMIC EVALUATION OF DRUGS IN PATIENTS OF PAINFUL DIABETIC NEUROPATHY

Aims and objectives: To study the effect of methylcobalamin, the combination of methylcobalamin with pregabalin, and methylcobalamin with duloxetine in patients with painful diabetic neuropathy after comparing the safety, tolerability, and economic implications of all three study groups. Methods: The present study was a prospective, open-labeled, interventional, randomized, and parallel-group study conducted on 100 patients of painful diabetic nephropathy from the outpatient department of the hospital who were recruited after obtaining informed consent. The permission for the study was taken from the Institutional Ethical Committee. The patients were randomized into three study groups: A, B, and C, on methylcobalamin, methylcobalamin, pregabalin, methylcobalamin, and duloxetine. Results: The mean value of the price of each tablet from all the brands of the respective drugs and finally calculating the cost for the whole 3 months which comes out to be Rs. 797.4 for group A, Rs. 1940.4 for group B, and Rs. 1163.7 for group C. The cost of the entire treatment and the effect produced in terms of the difference in the visual analog scale score from day 1 to the end of week 12 which are 0.58 for group A, 3.82 for group b, and 4.17 for group C. Conclusion: The primary purpose of the pharmacoeconomic evaluation is not to directly alter the therapeutic decisions of the physicians but to help the physicians, pharmacists, and policymakers to make informed decisions about whether the cost and extra benefits of the new drug are meaningful within the given budget.

Abstract A135: Are survival benefits of new drugs in combinations due to modest benefits in most patients or large benefits in few patients?

Abstract INTRODUCTION Combination therapy is a cornerstone in cancer treatment, often developed by adding new therapies to a standard-of-care treatment. However, clinical trials of adding a drug to a combination (A versus A+B) face an ambiguity in interpretation, because a higher Kaplan-Meier survival curve can result from modest benefits to overall survival (OS) or progression-free survival (PFS) in most patients, or from larger benefits in a few patients. This ambiguity exists even with complete patient data because no individual patient is simultaneous enrolled in control and test arms. Thus, clinical trials of drug combinations do not reveal the percentage of patients who benefit from an added drug and the extent of that benefit. METHODS We developed a deconvolution algorithm to estimate the distributions of survival benefits of new drugs in combination regimens. Among FDA approvals of combination therapies for advanced cancer between 1995 and 2020, we identified and analyzed 92 trials which compared a ‘standard-of-care’ control arm with ‘standard-of-care plus a new therapy’. We used deconvolution to infer all possible distributions of benefits of the new therapy. These possibilities differ by cross-resistance between drugs, and we therefore leveraged cross-resistance data from large-scale pre-clinical drug response encyclopedias to estimate the most likely distribution of survival benefits of new drugs. Our methods were further validated using patient-derived xenograft (PDX) studies and clinical monotherapy data. RESULTS Clinical trials with seemingly modest PFS or OS benefits from combination therapy were commonly explained by longer survival benefits in a minority of patients. Across many trials, on average 50% of patients experience a PFS or OS benefit of at least 1 month from new drugs, and median duration of benefit in such patients was on average 3 months longer than median benefit reported in the clinical trial. Data from the Novartis PDX encyclopedia (in which single tumors’ responses to both control and test treatments can be measured) confirmed that our deconvolution algorithm was successful at resolving the contributions of individual drugs in combinations. CONCLUSION We developed a broadly applicable method to estimate the proportion of patients that benefit from additional drugs and the durations of those benefits, thus resolving an ambiguity in the interpretation of drug combination trials. Most approved drug combinations had a proportion of patients who experienced much longer survival benefits than was visually apparent in Kaplan-Meier curves. These findings reconcile conflicting interpretations of drug trials in oncology, where health economists often see modest benefits, whereas clinicians observe long-lasting and worthwhile benefits in (some of) their patients. Seemingly modest survival benefits of new drugs in combinations may often be attributed to a lack of patient stratification rather than a lack of drug efficacy, which calls for greater use of biomarkers and precision strategies in the development of combination therapies. Citation Format: Haeun Hwangbo, Adam C Palmer. Are survival benefits of new drugs in combinations due to modest benefits in most patients or large benefits in few patients? [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A135.

How to Handle Elevated Triglycerides: Life after PROMINENT.

Hypertriglyceridaemia (HTG) is a common condition characterised by elevated levels of plasma triglycerides (TG), which are transported in the blood mainly by TG-rich lipoproteins (TRL). Elevated TG levels (150-400 mg/dL) are associated with increased cardiovascular risk. Severe HTG (>880 mg/dL) is associated with a risk of acute pancreatitis only. Randomised clinical trials investigating the clinical benefit of TG-lowering drugs in patients with elevated TG levels have provided conflicting results. Elevated TG levels are only one marker of altered lipid/lipoprotein metabolism and indeed reflect altered concentrations of one or more classes or subfractions of TRL, which in turn may have a different association with CV risk. Fibrates, the drugs most commonly used to treat HTG, provide cardiovascular benefits to only a specific subgroup of patients. The lack of clinical benefit from pemafibrate has emphasised the concept that lowering TG levels is not sufficient to reduce the CV risk unless it is accompanied by a reduction in the number of circulating atherogenic lipoproteins, which can be assessed by determining apolipoprotein B levels. Treatment with omega-3 fatty acids was also ineffective in reducing CV risk, with the exception of icosapent ethyl, which, however, appears to have beneficial effects beyond lipids. New drugs are currently being developed that aim to lower TG levels by targeting apolipoprotein C-III or angiopoietin-like-3, both of which are involved in the metabolism of TGs. TG reduction can be achieved by various drugs, but most of them are ineffective in reducing CV risk. The results of outcome studies on new TG-lowering drugs will clarify whether lowering apoB levels is critical to achieve clinical benefit.

How to Use Janus Kinase Inhibitors in the Treatment of Rheumatoid Arthritis? A Clinical Assessment of Risks and Benefits.

To provide an updated understanding of risks and benefits of Janus kinase inhibitors (JAKi) versus biologic disease-modifying antirheumatic drugs (bDMARDs) in the management of rheumatoid arthritis (RA). Shared decision-making is needed in choosing between JAKi and bDMARDs. Cardiovascular disease, malignancy, and thromboembolic events guide this choice. In patients with active RA despite methotrexate use, tumor necrosis factor inhibitor is conditionally favored over JAKi for low-cardiovascular-risk patients and strongly favored in those with pre-existing cardiovascular disease or multiple cardiovascular risk factors.Suboptimal treatment of treatment-refractory RApatients may pose a greater absolute cardiovascular risk than with JAKi use. Use of aspirin and statin may be considered to reduce cardiovascular risk. New safety data on JAKi has redefined the treatment approach in RA. JAKi remains an important oral medication option in active RA despite treatment with bDMARDs, especially in those with low cardiovascular risk.

HPR10 Added Benefit and Revenues of Oncology Drugs Approved By the European Medicines Agency between 1995 and 2020

HPR10 Added Benefit and Revenues of Oncology Drugs Approved By the European Medicines Agency between 1995 and 2020

A Comprehensive Review of Small Interfering RNAs (siRNAs): Mechanism, Therapeutic Targets, and Delivery Strategies for Cancer Therapy.

Small interfering RNA (siRNA) delivery by nanocarriers has been identified as a promising strategy in the study and treatment of cancer. Short nucleotide sequences are synthesized exogenously to create siRNA, which triggers RNA interference (RNAi) in cells and silences target gene expression in a sequence-specific way. As a nucleic acid-based medicine that has gained popularity recently, siRNA exhibits novel potential for the treatment of cancer. However, there are still many obstacles to overcome before clinical siRNA delivery devices can be developed. In this review, we discuss prospective targets for siRNA drug design, explain siRNA drug properties and benefits, and give an overview of the current clinical siRNA therapeutics for the treatment of cancer. Additionally, we introduce the siRNA chemical modifications and delivery systems that are clinically sophisticated and classify bioresponsive materials for siRNA release in a methodical manner. This review will serve as a reference for researchers in developing more precise and efficient targeted delivery systems, promoting ongoing advances in clinical applications.

Vasopressors and inotropes in cardiogenic shock patients: an analysis of the MIMIC-IV database

IntroductionPharmacological support has become the mainstay therapy in patients with cardiogenic shock (CS). Unfortunately, the clinical benefits of such potent drugs remain unclear, therefore, the present study aims to elucidate the safety and efficacy of vasoactive agents in CS patients.MethodsMedical Information Mart for Intensive Care (MIMIC) IV databases were used for this retrospective study. The primary outcome of this study was 30-day all-cause mortality. The subgroup analysis of was the relationship between the combined use of vasopressors and inotropes and 30-day all-cause mortality.ResultsA total of 2,216 patients diagnosed with CS were enrolled in this study. The non-survivors group was more likely to be older, presented with chronic kidney disease, have a lower systolic blood pressure, lower heart rate, and higher respiratory rate (all p &amp;lt; 0.05). In the multivariate Cox regression analysis, only dopamine [HR (95%CI): 1.219 (1.003–1.482)], norepinephrine [HR (95%CI): 2.528 (1.829–3.493)], and milrinone [HR (95%CI): 0.664 (0.512–0.861)] remained an independent predictor for 30-day all-cause mortality. Furthermore, a subgroup analysis was performed and found that no statistically significant difference between no vasopressor/inotrope use and 1 vasopressor/inotrope use (p = 0.107). Meanwhile, a substantial deterioration of cumulative survival was observed when a combination of 2 or more vasopressors/inotropes was used in CS patients in comparison with no vasopressor/inotrope or only 1 vasopressor/inotrope use (all p &amp;lt; 0.05).ConclusionsUsing vasopressors/inotropes agents was associated with a higher risk of 30-day all-cause mortality in CS patients. In addition, only milrinone was associated with a better prognosis among the available vasoactive agents.

Treatment Patterns and Healthcare Resource Utilization Among Patients with Triple Class Exposed Multiple Myeloma: A Population-Based Cohort Study

Introduction: Outcomes of patients with relapsed or refractory multiple myeloma (MM) have improved substantially with access to novel therapeutic agents. However, patients with triple class exposed (TCE) MM continue to have poor outcomes. Though newer bispecific antibody and chimeric antigen receptor T-cell immunotherapies have improved outcomes of TCE patients, these therapies are inaccessible outside of clinical trials in many publicly funded healthcare systems, including Canada. This study aimed to describe treatment patterns, outcomes, unplanned health care utilization and quality-of-life impairments of TCE MM patients in Ontario, Canada. These data will provide a crucial benchmark to compare to as novel immunotherapies become available. Methods: This retrospective observational study utilized data from the Institute for Clinical Evaluative Sciences (IC/ES) administrative database, which contains all health records of patients treated within Ontario's publicly funded healthcare system. Drug exposure was determined using the Cancer Activity Level Reporting (ALR) and Ontario Drug Benefit Claims Registry (ODB) databases, housed within IC/ES, which contain data on intravenous and oral MM treatment exposure for standard of care and clinical trial regimens. Patients were defined as TCE if they had prior or current treatment with a regimen containing an immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), and an anti-CD38 monoclonal antibody (isatuximab or daratumumab). The TCE index regimen was identified as the treatment on which a patient was first identified as having met the TCE definition. Inpatient hospitalization visits did not include planned chemotherapy infusion visits. Quality of life was described using the Edmonton Symptom Assessment System Score with scores ³ 7 corresponding to severe symptoms. Overall survival (OS) was determined using the Kaplan-Meier method. Results: Of the 16,777 patients with a diagnosis of MM between 2007-2021 in Ontario, 1358 patients were classified as TCE during their treatment course. The TCE index regimen was a daratumumab-based regimen in most patients [daratumumab/velcade/dex (n=566, 42%), daratumumab/lenalidomide/dex (n=619, 46%)]. Of the TCE patients, 247 (18%) were still receiving treatment with the TCE index regimen at last follow up, 263 (19%) died without receiving any additional treatment, and 489 (36%) received a subsequent MM treatment after the TCE index regimen. Baseline characteristics of patients (n=489) treated with a subsequent MM regimen after post TCE are summarized in Table 1. The three most commonly administered therapies post TCE were carfilzomib-dexamethasone (n=111, 23%), pomalidomide-dexamethasone (n=77, 16%) and oral cyclophosphamide (n=49, 10%). The next-line treatment regimen was administered in an academic versus community treatment center in 235 (48%) versus 254 (52%) of patients, respectively. The next-line therapy was a clinical trial in only 37 (8%) patients. Regarding healthcare utilization, among TCE patients receiving subsequent therapy, 149 (30%) were evaluated in the emergency department (ED), 126 (26%) were admitted to hospital, and 48 (10%) were referred to palliative care while on treatment with the subsequent therapy. Among patients with available information, the most common severe patient-reported symptoms during the subsequent line of treatment included: tiredness (27%), pain (23%) and overall poor well-being (21%). Additionally, 35% of patients had a ECOG PS of ≥2 on next-line treatment. The median OS patients treated after the TCE index regimen was 1.05 year (95% CI 0.89-1.35) as shown in Figure 1. Of the patients that died during follow up, the majority died in hospital (n=147, 44%) and were referred to palliative care (217, 65%). Conclusion: In this real-world study, we showed that the overall outcomes of TCE MM patients remains poor in Canada, highlighting the urgent need for novel therapies. Furthermore, we demonstrated that TCE patients receiving subsequent therapy had significant unplanned health care utilization and poor quality of life. Future studies will need to assess whether the outcomes, healthcare utilization, and patient-reported quality of life improve as newer immunotherapies become accessible as standard of care treatments within our publicly funded healthcare system.

Features of treatment of haemorrhoids in overweight patients

Hemorrhoidal disease is one of the most common proctological diseases in the population, covering, according to a number of authors, from 4 to 86% of the population over the age of 40 years. In addition, the problem of metabolic syndrome and accompanying obesity have become a real disease of the century in developed countries. This condition predisposes to a large number of diseases, including hemorrhoidal disease. From these positions, it is advisable to highlight the possibilities of treating not only hemorrhoids themselves, but also combating metabolic syndrome in this category of patients. The article describes modern data on the therapeutic effect of bioflavonoids, in particular hesperidin, and the mechanisms of their therapeutic action in acute and chronic hemorrhoids. The possibilities of using topical therapy for hemorrhoids are also highlighted, attention is paid to suppositories based on sodium alginate, thanks to which the drug has a hemostatic, anti-inflammatory and reparative effect, alleviating local symptoms of hemorrhoids and anal fissure. Data are provided on the therapeutic effect of the combination of hesperidin + diosmin in relation to the symptoms of hemorrhoids in patients with excess body weight and to metabolic syndrome are presented, as well as the experience of clinical observation in the hospital of the Faculty of Surgery No. 2 L/F of the N.I. Russian National Research Medical University is presented. Pirogov in the treatment of 1 300 comorbid patients with acute hemorrhoids and exacerbation of chronic hemorrhoids, followed by surgical treatment. The potential benefits of drugs with a standardized content of hesperidin (Venarus®) in relation to the treatment of hemorrhoids in patients with excess body weight and metabolic syndrome, comparison with other drugs from the group of bioflavonoids, are described.

Evolution of pharmacogenomic services and implementation of a multi-state pharmacogenomics clinic across a large rural healthcare system.

Introduction: Pharmacogenomics (PGx) aims to maximize drug benefits while minimizing risk of toxicity. Although PGx has proven beneficial in many settings, clinical uptake lags. Lack of clinician confidence and limited availability of PGx testing can deter patients from completing PGx testing. A few novel PGx clinic models have been described as a way to incorporate PGx testing into the standard of care. Background: A PGx clinic was implemented to fill an identified gap in provider availability, confidence, and utilization of PGx across our health system. Through a joint pharmacist and Advanced Practice Provider (APP) collaborative clinic, patients received counseling and PGx medication recommendations both before and after PGx testing. The clinic serves patients both in-person and virtually across four states in the upper Midwest. Results: The majority of patients seen in the PGx clinic during the early months were clinician referred (77%, n = 102) with the remainder being self-referred. Patients were, on average, taking two medications with Clinical Pharmacogenetics Implementation Consortium guidelines. Visits were split almost equally between in-person and virtual visits. Conclusion: Herein, we describe the successful implementation of an interdisciplinary PGx clinic to further enhance our PGx program. Throughout the implementation of the PGx clinic we have learned valuable lessons that may be of interest to other implementors. Clinicians were actively engaged in clinic referrals and early adoption of telemedicine was key to the clinic's early successes.