Drugs of the future for diarrhea-predominant irritable bowel syndrome: an overview of current investigational drugs.

INTRODUCTION: Irritable bowel syndrome (IBS) has a significant impact on society and quality of life. Current treatments are ineffective, and new investigational drugs are necessary. AREAS COVERED: Numerous potential therapies are developing, targeting different areas such as cannabinoid signaling, opioid receptors, tachykinin (NK2) receptors, ß3-adrenergic receptors, intestinal microbiota, inflammation, and 5HT receptors. Clinical trial evidence has shown that loperamide, eluxadoline, alosetron, ramosetron, bile acid sequestrants, and rifaximin can modulate GI alterations and benefit patients with IBS-D. Among the potential therapies, ibodutant, ibudilast, blautix, BOS-589, solabegron, vibegron, olorinab, ebastine, and ORP-101 have demonstrated possible effects but remain confirmed. EXPERT OPINION: Individuals with IBS-D require cost-effective treatment options that do not impede their productivity or that of their caregivers. This is necessary for consistent healthcare and improved quality of life. Therefore, we should focus on developing new, efficient, and affordable medications for IBS-D. The government, insurers, and society must recognize this need and collaborate to ensure its fulfillment.

Choosing the Best Instrument for Measuring Health Spillover Effect in Caregivers of Patients With Multiple Sclerosis.

OBJECTIVES: To measure the health spillover effect in caregivers of patients with multiple sclerosis (MS), we aimed to select the best instrument from 2 common health-related quality of life (QoL) instruments, the 3-level EQ-5D (EQ-5D-3L) and the Health Utilities Index Mark 3 (HUI-3), by assessing them. METHODS: Using consecutive sampling, 452 primary caregivers of patients with MS were asked to fill out a Care-related QoL instrument (CarerQol-7D), EQ-5D-3L, HUI-3, and the Center for Epidemiologic Studies Depression Scale between October 2019 and May 2020. Convergent and clinical validity were assessed to measure spillover effect in caregivers of patients with MS. RESULTS: A strong correlation of health-utility scores between EQ-5D-3L and HUI-3 (r = 0.914, P < .01) was observed. The 95% limit of agreement (LoA) for CarerQol-7D and HUI-3 (-10.6 to 8.2) was narrower than the LoA for CarerQol-7D and EQ-5D-3L (-15.1 to 17.1). Both EQ-5D-3L and HUI-3 proved clinical validity for the QoL of caregivers. The CarerQoL-7D score was significantly lower in female (P < .001), single (P < .014), lower-educated (P < .001), parent's relatives (P < .001), and unemployed (P < .001) caregivers. CONCLUSIONS: We found that both, EQ-5D-3L and HUI-3, were appropriate for measuring caregivers' QoL, although HUI-3 was a better choice because of its narrower LoA. Our findings suggest researchers should use HUI-3 to measure the quality-adjusted life-year of caregivers to aggregate with the QoL of patients in the denominator of an economic evaluation equation, such as the cost-effective ratio.

Advancements in pharmacotherapy options for treating diabetes in children and adolescents.

INTRODUCTION: This study compares diabetes management between pediatric and adult patients and identifies treatment challenges and gaps. AREAS COVERED: We searched PubMed and Clinicaltrails.gov databases for studies published from 2001 to 2023 on diabetes management in different age groups. EXPERT OPINION: Research shows children have lower insulin sensitivity, clearance, and ß cell function than adults. The US FDA only allows insulin, metformin, and liraglutide as antidiabetic medication options for children. However, some off-label drugs, like meglitinides, sulfonylureas, and alogliptin, have demonstrated positive results in treating certain types of diabetes caused by gene mutations. It's crucial to adopt personalized and precise approaches to managing diabetes in pediatrics, which vary from those used for adult patients. New studies support the classification of type 2 diabetes into several subtypes based on age, BMI, glycemia, homeostasis model estimates, varying insulin resistance, different rates of complications , and islet autoantibodies. With this insight, prevention, treatment, and precision medicine of diabetes might be changed. More research is necessary to assess the safety and efficacy of different antidiabetic drugs and improve diabetes treatment for children and adolescents.

A cost-effectiveness analysis of linagliptin add-on to insulin treatment for patients with type 2 diabetes mellitus and chronic kidney disease in Iran.

Purpose: With the high prevalence of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM), determining optimal treatment strategies has become a major concern. Linagliptin is aDPP-4 inhibitor that does not require dose adjustment in patients with renal impairment. This study evaluates the cost-effectiveness of adding linagliptin to insulin therapy in patients with T2DM and mild (stage 2) or moderate (stage 3) CKD from a health system perspective in Iran. Methods: We developed a cost-utility model using a decision tree and ran it separately for T2DM patients with mild or moderate CKD. Clinical outcomes and health-state utility values were extracted from published studies. Direct medical costs were obtained from national tariffs in Iran in 2021. We adopted an annual time horizon and calculated the difference in costs and quality-adjusted life-years (QALYs) to obtain the incremental cost-effectiveness ratios (ICER). To capture parameter uncertainties, one-way sensitivity analyses were also performed. Results: In T2DM patients with mild CKD, the linagliptin add-on strategy was associated with an additional $23.69 cost and 0.0148 QALYs per patient, resulting in an ICER of 1600.37 USD/QALY. In moderate CKD, the strategy was associated with $22.59 more costs and 0.0191 more QALYs, and the ICER was estimated at 1182.72 USD/QALY. In both populations, the ICER was mainly driven by the impact of HbA1c on utility, cost of linagliptin, and the reduction in insulin usage by adding linagliptin to the treatment. Conclusion: With a cost-effectiveness threshold of $1550 USD/QALY in Iran, adding linagliptin to insulin is cost-effective in patients with T2DM and moderate CKD. However, for those with mild CKD, it seems that the associated costs outweigh the expected benefits. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01243-z.

Towards greater impact in health technology assessment: System dynamic approach for new and emerging technologies in Iran.

PURPOSE: As classical health technology assessment models fail to predict the complexities of related impacts, the application of modeling techniques such as systems dynamics simulation (SD) is essential. This study aimed to develop an SD model to predict the outcomes of access to a new medicine in Iran. METHODS: This study extracted the important and influential variables in providing access to new pharmaceutical technologies by comprehensively reviewing previous research and combining the technical knowledge of experts in this field. The variables were incorporated into the systems thinking framework and modeled using dynamic systems tools, followed by simulation and testing in VENSIM. The model was piloted for deferoxamine and deferasirox in thalassemia. Various tests were used to evaluate the validity and reliability of the model. The model was designed for a ten-year horizon (2018-2028) for medicines selected as the pilot. RESULTS: The variables extracted from the panel of experts encompassed the primary and short-term impacts of access to newly emerged medicine and long-term impacts regarding the economy, health, and society. After modeling, the leverage points presented for the problem with the greatest impact or effectiveness in access to new medicine included the policy determining the amount of medicine supply, the import and production of medicine, the prevalence and incidence of disease, insurance coverage, and treatment adherence. CONCLUSION: The SD models allow the researchers to evaluate the efficiency and health outcomes of a new pharmaceutical more precisely in the health system in Iran.

Common gastrointestinal drug-drug interactions in geriatrics and the importance of careful planning.

INTRODUCTION: Polypharmacy, which uses multiple medications to treat chronic illnesses, is common among elderly patients. However, it can lead to drug interactions, especially with gastrointestinal (GI) medicines that are extensively used. These drug interactions can have severe consequences and pose a significant challenge to healthcare providers. Therefore, it is crucial to identify the underlying mechanisms of these interactions and develop strategies to minimize medication errors. AREAS COVERED: We analyzed databases on GI illnesses common in older adults, including GERD, peptic ulcer disease, IBS, IBD, constipation, and diarrhea. Our research identified noteworthy drug interactions and utilized major electronic databases such as USFDA, PubMed, Scopus, and Google Scholar until 15 May 202315 May 2023, along with a review of reference lists. EXPERT OPINION: Aging can affect how the body processes drugs, leading to an increased risk of drug interactions. Therefore, healthcare professionals must carefully evaluate a patient's medical history and health condition to design personalized treatment plans.

Pharmacotherapy for gastric and intestinal cramping pain: current and emerging therapies.

INTRODUCTION: Acute gastrointestinal cramping pain (GICP) is a debilitating condition that affects many people worldwide, significantly reducing their quality of life. As such, prompt treatment is crucial. AREAS COVERED: This article will explore relevant literature from databases such as PubMed, Scopus, Google Scholar, Cochrane Library, and Web of Science. Additionally, we searched ClinicalTrials.gov and the WHO ICTRP database for the latest clinical trials. EXPERT OPINION: Consensus dictates that antispasmodics such as hyoscine-N-butyl bromide and mebeverine should be the primary treatment for GICP. If these prove ineffective, patients can switch to an antispasmodic with a different mode of action or add acetaminophen/NSAIDs for more severe cases. Currently, several antispasmodics are undergoing clinical trials, including drotaverine, alverine, pinaverium, otilonium bromide, fenoverine, tiropramide, otilonium bromide, trimebutine, and peppermint oil. Well-designed head-to-head studies are necessary to evaluate current antispasmodics' safety, efficacy, pharmacokinetic, and pharmacoeconomics profiles. Recent studies have shown that fixed-dose combinations of antispasmodics + NSAIDs or two different antispasmodics can improve patient compliance and synergistically reduce GICP. Therefore, it is recommended that the global availability and accessibility of these products be enhanced.

Cost-effectiveness and budget impact analysis of lisdexamfetamine versus methylphenidate for patients under 18 with attention-deficit/hyperactivity disorder in Iran.

BACKGROUND: Lisdexamfetamine (LDX) and Methylphenidate (MPH) are stimulant agents that have been shown to provide significant benefits in the management of attention-deficit/hyperactivity disorder (ADHD) in patients. AIM: This study aimed to assess the cost-effectiveness and the budget impact of LDX compared to MPH as the first-line treatment for ADHD. METHODS: A one-year cost-effectiveness analysis (CEA) was conducted to compare the effects of LDX and MPH in reducing disease symptoms and patient costs and improving quality of life (QoL) from a social perspective. Clinical data were obtained using the EQ-5D questionnaire. In contrast, economic data were sourced from the official website of the Iranian Food and Drug Association (FDA), the national book of tariffs, and specific questionnaires designed to evaluate patients' direct and indirect costs. 197 patients were included in the study, including individuals who sought psychiatric evaluation at a hospital in Mashhad and those who obtained ADHD medications from governmental pharmacies. The cost-effectiveness of the study medicine was assessed using the decision tree method, and the results were presented as the Incremental Cost-Effectiveness Ratio (ICER). Deterministic Sensitivity Analysis (DSA) and Probabilistic Sensitivity Analysis (PSA) were performed to assess the robustness of the findings. Additionally, a Budget Impact Analysis (BIA) was conducted over five years, considering three different scenarios, to evaluate the financial implications of incorporating LDX into the national pharmaceutical system. RESULTS: The ICER for LDX therapy compared to MPH was estimated at USD 264.28 (with an incremental cost of USD 54.9, incremental effectiveness of 0.208, and Quality-Adjusted Life Years (QALYs) gained of 0.765). The PSA indicated a 0.994% probability of LDX being cost-effective, considering a threshold of USD 2450 per QALY. Furthermore, the DSA revealed that the acquisition cost of LDX influenced the model's sensitivity. The BIA demonstrated that incorporating LDX into Iran's healthcare system would result in a financial burden of approximately $368,566 in the first year, representing an additional cost of $11,154 compared to the non-availability of this medicine and the use of previous medications. It is projected that by 2027, the financial burden of treating ADHD with LDX will reach approximately USD 443,879 over five years, amounting to an increase of $71,154 compared to the absence of this medicine. CONCLUSION: From a social perspective, the inclusion of LDX in the treatment regimen for ADHD is associated with higher costs and an increased financial burden. However, based on our analysis, LDX appears to be a cost-effective choice for managing ADHD in Iran when compared to MPH.

Cost-Effectiveness Comparison between Ticagrelor and Clopidogrel in Acute Coronary Syndrome in Iran.

Background: The present study aimed to determine the cost-effectiveness of ticagrelor compared with clopidogrel in Iranian patients with acute coronary syndrome (ACS). Methods: A 1-year decision tree model combined with a 20-year Markov transition model was used to simulate the long-term cost and effectiveness of both ticagrelor and clopidogrel in Iran based on an Iranian payer's perspective. Clinical efficacy data were extracted from the PLATO trial and other published studies. Costs were estimated based on local prices in public sectors. Deterministic and probabilistic sensitivity analyses were used to test the robustness of base-case results over the uncertainties of model inputs. All calculations, analyses, and modeling were done in TreeAge 2011 and Microsoft Excel 2013. Results: Compared with clopidogrel, the treatment of Iranian ACS patients with ticagrelor for 20 years resulted in an additional cost of US$ 2.39 in a hypothetical cohort of 1000 patients. However, ticagrelor led to 7.2 quality-adjusted life-years (QALYs) gained per 1000 hypothetical patients. Accordingly, the estimated incremental cost-effectiveness ratio for this analysis was US$ 332.032 per 1 QALY gained. Conclusion: Ticagrelor was a cost-effective antiplatelet medicine compared with clopidogrel in Iranian patients with ACS. This could help Iran's policymakers to allocate resources more efficiently to ACS.

An updated systematic review and dose-response meta-analysis on the relation between exposure to arsenic and risk of type 2 diabetes.

Arsenic is among the most critical environmental toxicants associated with many human disorders. However, its effect on type 2 diabetes mellitus (T2DM) is contradictory. This systematic review and dose-response meta-analysis aim to update information on the association between arsenic exposure and the risk of T2DM. The sample type (drinking water, urine, blood, and nails) conducted the subgroup analysis. Evaluation of the high vs. low arsenic concentrations showed a significant association between drinking water arsenic (OR: 1.58, 95% CI: 1.20-2.08) and urinary arsenic (OR: 1.37, 95% CI: 1.24-1.51) with the risk of T2DM. The linear dose-response meta-analysis showed that each 1 µg/L increase in levels of drinking water arsenic (OR: 1.01, 95% CI: 1.00-1.01) and urinary arsenic (OR: 1.01, 95% CI: 1.00-1.02) was associated with a 1% increased risk of T2DM. The non-linear dose-response analysis indicated that arsenic in urine was associated with the risk of T2DM (Pnon-linearity<0.001). However, this effect was not statistically significant for arsenic in drinking water (Pnon-linearity=0.941). Our findings suggest that blood arsenic was not significantly linked to the increased risk of T2DM in high vs. low (OR: 1.21, 95% CI: 0.85-1.71), linear (OR: 1.04, 95% CI: 0.99-1.09), and non-linear (Pnon-linearity=0.365) analysis. Also, nail arsenic was not associated with the risk of T2DM in this meta-analysis (OR: 1.33, 95% CI: 0.69-2.59). This updated dose-response meta-analysis indicated that arsenic exposure was significantly correlated with the risk of T2DM.

Upfront DPYD Genotype-Guided Treatment for Fluoropyrimidine-Based Chemotherapy in Advanced and Metastatic Colorectal Cancer: A Cost-Effectiveness Analysis.

OBJECTIVES: Fluoropyrimidines are the most widely used chemotherapy drugs for advanced and metastatic colorectal cancer (CRC). Individuals with certain DPYD gene variants are exposed to an increased risk of severe fluoropyrimidine-related toxicities. This study aimed to evaluate the cost-effectiveness of preemptive DPYD genotyping to guide fluoropyrimidine therapy in patients with advanced or metastatic CRC. METHODS: Overall survival of DPYD wild-type patients who received a standard dose and variant carriers treated with a reduced dose were analyzed by parametric survival models. A decision tree and a partitioned survival analysis model with a lifetime horizon were designed, taking the Iranian healthcare perspective. Input parameters were extracted from the literature or expert opinion. To address parameter uncertainty, scenario and sensitivity analyses were also performed. RESULTS: Compared with no screening, the genotype-guided treatment strategy was cost-saving ($41.7). Nevertheless, due to a possible reduction in the survival of patients receiving reduced-dose regimens, it was associated with fewer quality-adjusted life-years (9.45 vs 9.28). In sensitivity analyses, the prevalence of DPYD variants had the most significant impact on the incremental cost-effectiveness ratio. The genotyping strategy would remain cost-saving, as long as the genotyping cost is < $49 per test. In a scenario in which we assumed equal efficacy for the 2 strategies, genotyping was the dominant strategy, associated with less costs (∼$1) and more quality-adjusted life-years (0.1292). CONCLUSIONS: DPYD genotyping to guide fluoropyrimidine treatment in patients with advanced or metastatic CRC is cost-saving from the perspective of the Iranian health system.

Pharmacoeconomic evaluation of insulin aspart and glargine in type 1 and 2 diabetes mellitus in Iran.

Purpose: The higher costs of insulin analogs including short-acting insulin aspart (IAsp) and long-acting insulin glargine (IGla) have restricted their widespread uptake despite having improved pharmacokinetic and pharmacodynamic properties and patient convenience. This study aims to evaluate the cost-effectiveness of IAsp versus Regular Insulin (RI) and IGla versus NPH Insulin in type 1 and 2 diabetes from the perspective of the Iranian healthcare system. Methods: Clinical data including HbA1c levels, hypoglycemia, weight gain, and health-related quality of life were derived from the included systematic review and meta-analysis studies. Different methods of pharmacoeconomic evaluation were used for an annual time horizon. Utility decrements for diabetes-related complications were extracted from the literature. Direct medical costs were calculated in 2022 prices. A one-way sensitivity analysis was also performed. Results: In type 1 diabetes, IAsp was associated with more costs and effects in terms of reducing HbA1c compared with RI. An incremental cost of $83 was estimated to obtain an additional 1% reduction in HbA1c per patient per year. Similarly, an incremental cost of $16 was estimated for IGla compared with NPH. In type 2 diabetes, IAsp and RI were associated with equal efficacy and safety. For IGla versus NPH, the incremental cost-effectiveness ratio was calculated at $1975 per quality-adjusted life-year. The robustness of the result was confirmed through sensitivity analysis. Conclusion: Insulin analogs, IAsp and IGla, are cost-effective for type 1 diabetes versus human insulins, RI and NPH. For type 2 diabetes, IAsp is not cost-effective when compared with RI. For IGla versus NPH, however, the incremental cost-effectiveness ratio seems to be within the accepted thresholds.

How do patients value features of biological medicine in rheumatoid arthritis? A discrete choice experiment.

BACKGROUND: The aim of this study was to quantify the preference of the patients regarding biological DMARDs. RESEARCH DESIGN AND METHODS: Patients' preferences were assessed using a discrete choice experiment. Eighteen different surveys describing eight attributes were designed using experimental design methods. Each survey presented eight choice tasks with two options for patients to choose one. A conditional logit model was used to calculate relative importance and willingness to pay. Subgroup analysis was conducted to evaluate the effect of the patients' characteristic on their preferences. RESULTS: A total of 306 patients were included in the study. All attributes had significant effects on the patients' choices. The most important feature was the ability to preserve physical function. The least important feature was the route of administration. Surprisingly, the out-of-pocket cost was one of the last priorities for respondents. According to the relative importance calculations, 80% of the patients' preferences can be obtained by clinical attributes. Based on subgroup analysis, the most important patient characteristic that affected their choices was the monthly out-of-pocket history. CONCLUSIONS: Different features of treatment had different effects on the patients' preferences. Quantification of the impact of each attribute not only revealed their relative importance but also determined the trade-off rate among them.

An update on the use of pharmacotherapy for opioid-induced bowel dysfunction.

INTRODUCTION: With the growing rate of aging and the incidence of chronic diseases, there has been an upsurge in opioid prescription and abuse worldwide. This has been associated with increased reports of opioid-related adverse events, particularly opioid-induced bowel dysfunction (OIBD), calling for a rational clinical management strategy. AREAS COVERED: Through searching PubMed, Scopus, Cochrane Library, and Web of Science, English literature was gathered as of 1 January 2017. Furthermore, the USFDA, EMA, TGA, Clinicaltrials.Gov, WHO-ICTRP databases, and the latest guidelines were reviewed to extract ongoing clinical studies and provide an evidence-based expert opinion with detailed information on efficacy, safety, approval status, and pharmacokinetics of the currently used medications. EXPERT OPINION: Despite the significant burden of OIBD, the clinical development of agents lags behind disease progress. Although in most places, management of opioid-induced constipation (OIC) is initiated by lifestyle modifications followed by laxatives, opioid antagonists, and secretagogue agents, there are still major conflicts among global guidelines. The fundamental reason is the lack of head-to-head clinical trials providing inter- and intragroup comparisons between PAMORAs, laxatives, and secretagogue agents. These investigations must be accompanied by further valid biopharmaceutical and economic evaluations, paving the way for rational clinical judgment in each context.

Therapeutic effects of dietary antioxidative supplements on the management of type 2 diabetes and its complications; umbrella review of observational/trials meta-analysis studies.

Background: Controversial data on the effects of vitamins (V) and nutrients on the management of type 2 diabetes mellitus (T2DM) is available. Thus, it is aimed to clarify the role of vitamins and nutrients through an umbrella review regarding the available observational/ trials meta-analyses. Methods: All meta-analyses of observational and clinical trials conducted on the impact of vitamins and nutrients in T2DM published until 5th June 2021 in PubMed or Web of Sciences were included in this review. Also, the meta-analysis on children, pregnant women, type 1 DM, or in vivo/in vitro studies was excluded. Search results were reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) flowchart. Results: The overall of 93 papers (99 studies) consisting of 75 trials and 24 observational studies were included. Most studies were conducted on the effect of VD and alpha-lipoic acid (ALA) in both genders. Consumption of VD or its analogous; 20 IU/d to 450,000 IU/once for 3 weeks to 7 years showed to have a positive effect on the parameters of glucose hemostasis. Moreover, an inverse association was observed between VD level and T2DM risk. Daily consumption of 1200 mg VC for at least 12 weeks improved lipid profile and glucose hemostasis parameters. Furthermore, VB and medications for diabetic polyneuropathy (DPN) increased nerve conduction velocity. Vitamins K and E were showen to not have significant impact on T2DM. ALA had a beneficial effect on DPN symptoms after 2-4 weeks of intake of at least 300 mg/d. T2DM risk was reduced by doubling ALA intake. The effective daily doses of chromium, zinc and coenzyme Q10 on lipid profile and glucose hemostasis parameters were > 200 mg, < 25 mg, and < 200 mg, respectively. Conclusion: This umbrella review suggests that dietary vitamins and nutrients can result in protective impacts the complications associated with T2DM. However, due to discrepancies between the results of the trials and observational studies is essential to conduct long-term high-qualified studies to prove the beneficial therapeutic effects of the vitamins and nutrients on T2DM and its complications.

Evaluation of COVID-19 Treatments in Iran in Comparison with Local Therapeutic Recommendations: A Population-Level Study on Utilization and Costs of Prescription Drugs.

Objective: In this study, we assess population-level data of COVID-19 treatments in Iran compared to Ministry of Health (MOH)-published guidelines to gain a better insight into the quality of care for this disease. Methods: National sales data of each recommended and nonrecommended COVID-19 medicine were used to proxy utilization between March 21, 2020, and March 21, 2021, or Iranian year 1399. COVID-19-attributed sales volume and number of patients were estimated by adjusting sales data with pre-COVID-19 average growth rate, recommended dose, and duration of treatment. Next, they were compared with the MOH guidelines in outpatient and inpatient settings. Furthermore, the list of top 10 molecules of the market and top 10 COVID-19-indicated molecules in terms of values were extracted to assess the economic burden of COVID-19 prescription drugs and their share. Findings: The estimated number of patients receiving COVID-19 treatments in some outpatient medicines such as recommended hydroxychloroquine was over 2.2 million. Favipiravir and remdesivir were collectively about two inpatient medicines 260,000; however, neither of these two medicines was recommended in the MOH guidelines. In some fewer specific medicines such as dexamethasone, prednisolone, azithromycin, and naproxen, the estimated number of COVID-19-attributed patients were incomparable with the officially announced number of confirmed cases in the year of study, which could be related to nonconfirmed diagnosed cases, irrational use, or prescribing, or limitations of our data and study. The total COVID-19-attributed market of candidate medicines was over 15 trillion IR Rials (almost 4.3% of the total market). Remdesivir, with over 60% of the total COVID-19 attributed market, followed by favipiravir, was among the highest value medicines. Conclusion: Despite the release of the COVID-19 guideline by Iran MOH, misalignment in the enforcement of decisions was a serious weakness (cases of favipiravir and remdesivir). This weakness led to some economic burden on the health-care system and raised ethical concerns.

A scoping review on patient heterogeneity in economic evaluations of precision medicine based on basket trials.

INTRODUCTION: Considerable challenges in the economic evaluation of precision medicines have been mentioned in previous studies. However, they have not addressed how an economic assessment would be conducted based on basket trials (novel studies for evaluation of precision medicine effects) in which the included populations have specific biomarkers and various cancers. Since basket trial populations have remarkable heterogeneity, this study aims to investigate the concept of heterogeneity and specific method(s) for considering it in economic evaluations through guidelines and studies that could be applicable in economic evaluation based on basket trials. AREA COVERED: We searched PubMed, Web of Science, Scopus, Google Scholar, and Google to find studies and pharmacoeconomics guidelines. The inclusion criteria included subjects of patient heterogeneity and suggested explicit method(s). Thirty-nine guidelines and 43 studies were included and evaluated. None of these materials mentioned disease types in a target population as a factor causing heterogeneity. Moreover, in economic evaluations, patient heterogeneity has been considered with four general approaches subgroup analysis, individual-based models, sensitivity analysis, and regression models. EXPERT OPINION: Type of disease is not considered a contributing factor in population heterogeneity, and the probable appropriate method for this issue could be individual-based models.

Precision medicine journey through omics approach.

It has been well established that understanding the underlying heterogeneity of numerous complex disease process needs new strategies that present in precision medicine for prediction, prevention and personalized treatment strategies. This approach must be tailored for each individual's unique omics that lead to personalized management of disease. The correlation between different omics data should be considered in precision medicine approach. The interaction provides a hypothesis which is called domino effect in the present minireview. Here we review the various potentials of omics data including genomics, transcriptomics, proteomics, metabolomics, pharmacogenomics. We comprehensively summarize the impact of omics data and its major role in precision medicine and provide a description about the domino effect on the pathophysiology of diseases. Each constituent of the omics data typically provides different information in associated with disease. Current research, although inadequate, clearly indicate that the information of omics data can be applicable in the concept of precision medicine. Integration of different omics data type in domino effect hypothesis can explain the causative changes of disease as it is discussed in the system biology too. While most existing studies investigate the omics data separately, data integration is needed on the horizon of precision medicine by using machine learning.

The importance of personalized medicine in urological cancers.

A better understanding of key regulatory pathways involved in cancers has led to the development of molecularly targeted therapies. Molecular profiling based on genomics, proteomics, and metabolomics in tumors provides clinicians with the necessary information to maintain a personalized therapeutic regimen according to the patient's needs. for example, androgen deprivation therapy (ADT) for advanced prostate cancer is one of the earliest forms of targeted therapy and has remained a choice of treatment by physicians. Unfortunately, most patients will eventually become non-responsive to ADT and succumb to the disease. Since the emergence of ADT, the understanding of androgen receptor (AR) signaling and mechanisms driving the resistance to ADT has been significantly improved. Inactivation of the PTEN gene is a common occurrence in prostate cancers and is associated with metastatic potential, androgen independence, and poor prognosis. Several studies over personalized medicine for muscle-invasive and metastatic bladder cancer discussed potential molecular biomarkers which are currently under investigation and based on the excision repair cross-complementing group 1 (ERCC1) gene and its role in tumor development and therapeutic resistance to cytotoxic DNA-damaging chemotherapy and ionizing radiation. In this review, we consider personalized medicine for four urological cancers.

Role of genetic polymorphisms in recurrent aphthous stomatitis: A systematic review and meta-analysis.

Recurrent aphthous stomatitis (RAS) is one of the most common oral ulcerative diseases with unknown etiology. Identifying the genetic markers can improve medical care and prevention of RAS. Genetics variants inflammatory agents are associated with the risk of RAS. Thus, this meta-analysis aimed to investigate the genetic polymorphisms in RAS. Electronic literature search was carried out on Scopus, PubMed, and Web of Science (WOS). The references of relevant reviews were also manually checked. The observational studies till the end of 2020 were included. Odds ratio (OR) was estimated by fixed and random effect model. Seventeen polymorphisms in 23 studies were included in analysis. Pooled analysis performed for 12 polymorphisms (IL-2+166, IL-2-330, IL-4-590, IL-4 RA1902, IL-6-597, TNF-α-308, NLRP3(rs4612666, rs10754558), MMP2- rs2285053, MMP9- rs11697325, MMP9- rs3918242, MMP9- rs17576, IL-1a-889, IL-10-819, and IL-12+1188). The meta-analyses carried out for six polymorphisms (IL-1ß-511, IL-1ß+3954, IL-6-174, IL-10-592, IL-10-1082, and serotonin transporter). There were following significant results for IL-10, 819 in allelic:1.46(1.04-2.05) and homozygote: 1.61(1.08-2.39) models, serotonin Transporter in allelic:0.53(0.40-0.71), recessive:0.56(0.35-0.90), dominant:0.35(0.22-0.57) and homozygote:0.30(0.17-0.54) models. IL-1ß-511 in dominant 0.69(0.50-0.95) and overdominant 0.73(0.55-0.96) models, IL-1ß+3954 in allelic 1.25(1.05-1.50), homozygote 1.67(1.05-2.63) and dominant 1.26(1.01-1.57) models, IL-6-174 in dominant 2.24(1.36-3.67), IL-10-592 in homozygote 0.41(0.23-0.72) and dominant 0.55(0.33-0.93), IL-10-1082 in allelic 1.19(1.01-1.39) and dominant 1.29(1.02-1.64). In conclusion, serotonin transporter(L/S), IL-10-819(T/C), IL-10-592(C/A), IL-10-1082(G/A), IL-1ß-511(C/T), IL-6-174(G/C), and IL-1ß+3954 (T/C) polymorphisms are associated with susceptibility to RAS. These variants could be potential predictors of RAS and could be used for the developing clinically effective genetic panel for RAS.