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.

Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing.

Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.

A Scoping Review of Different Methods of Assessing the Impact of New Medical Technologies at Early Stages of Development.

Background: Investing in the R & D sector of new medical technologies is associated with the risk of being rejected by paying organizations because of the lack of value-for-money. The purpose of this study is to investigate the different methods of evaluating the impacts of emerging medical technologies. Methods: Using scoping review method, we analyzed studies that investigated methods for assessing the impacts of emerging medical technologies on development. To find these studies, the Cochran Library, ISI Web of Knowledge, Embase, Ebsco and Pubmed databases from 2000 to 2018 were searched. The methodological quality of the studies was assessed using the STROBE Checklist. Two reviewers independently selected the qualified studies. Charting and collating the data were used based on the method proposed by Arksey and O'Malley. Results: Overall, 38 studies met the inclusion criteria. Sixteen methods were identified and put in five distinct categories: forecasting, Pro-HTA, Early-HTA, priority setting, and HHS were found to measure the impact of emerging technologies. The quality of these studies was acceptable. Few studies were conducted on emerging pharmaceutical technologies, and they were mostly on emerging medical devices. The Early HTA methods were often used to measure the effects of pharmaceutical technologies and medical devices technologies. The Pro-HTA method used dynamic modeling to examine the impact of medical technologies on a broad range of dimensions, while the HTA and Early-HTA methods used cost-effectiveness techniques throughout the development process. The HHS method used a multivariate decision-making technique. Conclusion: Different methods were used to investigate the impacts of emerging medical technologies. Chronologically Pro-HTA methods are new ways for investigating emerging medical technologies beyond clinical and economic impacts. Assessing the feasibility of implementing Pro-HTA in real environments deserves further research.

Effect of the herbal medicines in obesity and metabolic syndrome: A systematic review and meta-analysis of clinical trials.

Obesity is a medical situation in which excess body fat has gathered because of imbalance between energy intake and energy expenditure. In spite of the fact that the variety of studies are available for obesity treatment and management, its "globesity" still remains a big challenge all over the world. The current systematic review and meta-analysis aimed to evaluate the efficacy, safety, and mechanisms of effective herbal medicines in the management and treatment of obesity and metabolic syndrome in human. We systematically searched all relevant clinical trials via Web of Science, Scopus, PubMed, and the Cochrane database to assess the effects of raw or refined products derived from plants or parts of plants on obesity and metabolic syndrome in overweight and obesity adult subjects. All studies conducted by the end of May 2019 were considered in the systematic review. Data were extracted independently by two experts. The quality assessment was assessed using Consolidated Standards of Reporting Trials checklist. The main outcomes were anthropometric indices and metabolic syndrome components. Pooled effect of herbal medicines on obesity and metabolic syndrome were presented as standardized mean difference (SMD) and 95% confidence interval (CI). A total of 279 relevant clinical trials were included. Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredients were found to be effective in the management of obesity and metabolic syndrome. In addition, C. fimbriata, flaxseed, spinach, and fenugreek were able to reduce appetite. Meta-analysis showed that intake of green tea resulted in a significant improvement in weight ([SMD]: -0.75 [-1.18, -0.319]), body mass index ([SMD]: -1.2 [-1.82, -0.57]), waist circumference ([SMD]: -1.71 [-2.66, -0.77]), hip circumference ([SMD]: -0.42 [-1.02, -0.19]), and total cholesterol, ([SMD]: -0.43 [-0.77, -0.09]). In addition, the intake of P. vulgaris and N. sativa resulted in a significant improvement in weight ([SMD]: -0.88, 95 % CI: [-1.13, -0.63]) and triglyceride ([SMD]: -1.67, 95 % CI: [-2.54, -0.79]), respectively. High quality trials are still needed to firmly establish the clinical efficacy of the plants in obesity and metabolic syndrome.

A review on inputs and outputs in determining the efficiency of universities of medical sciences by data envelopment analysis method.

Background: Increasing the number of students in universities, simultaneously limiting allocation of funds to them, and maintaining the highest efficiency level in education and research are of paramount importance. There are several methods to assess the efficiency of universities, and one of the most widely used of which is data envelopment analysis (DEA). The aim of this study was to determine the input and output criteria to evaluate the efficiency of universities of medical sciences through review-related articles using the DEA method. Methods: The time limit for retrieving articles was considered from the beginning of the publication of the first paper in this field until the end of 2017. The data were retrieved from Web of Science, Scopus, Ovid, ProQuest, Science Direct, and PubMed using advanced searches. Inclusion criteria were as follow: relevancy of the articles to the purpose of the research, availability of the articles' full-text, articles published to the end of 2017, and articles published in English. Results: The most inputs used in the literature to determine university efficiency were number of academic staffs, budget and costs, number of students, number of nonacademic staffs, spaces, and equipment and student's entrance scores. Also, the most outputs used in the literature to determine university efficiency were number of graduates, publications, incomes, number of students, and student's scores. Conclusion: This study showed that a large number of researchers have focused on measuring and comparing the efficiency of universities to improve efficiency, reduce costs, and manage the resources. Efficiency analysis by DEA allows the policymakers to define and develop policies and guidelines to improve their performances.

Evaluation of the effectiveness of infusion of bone marrow derived cell in patients with heart failure: A network meta-analysis of randomized clinical trials and cohort studies.

Background: The aim of this study was to investigate the effectiveness of bone marrow-derived cells (BMC) technology in patients with heart failure and compare it with alternative therapies, including drug therapy, cardiac resynchronization therapy pacemaker (CRT-P), cardiac resynchronization therapy defibrillator (CRT-D). Methods: A systematic review study was conducted to identify all clinical studies published by 2017. Using keywords such as "Heart Failure, BMC, Drug Therapy, CRT-D, CRT-P" and combinations of the mentioned words, we searched electronic databases, including Scopus, Cochrane Library, and PubMed. The quality of the selected studies was assessed using the Cochrane Collaboration's tool and the Newcastle-Ottawa. The primary and secondary end-points were left ventricular ejection fraction (LVEF) (%), failure cases (Number), left ventricular end-systolic volume (LVES) (ml), and left ventricular end-diastolic volume (LVED) (ml). Random-effects network meta-analyses were used to conduct a systematic comparison. Statistical analysis was done using STATA. Results: This network meta-analysis covered a total of 57 final studies and 6694 patients. The Comparative effectiveness of BMC versus CRT-D, Drug, and CRT-P methods indicated the statistically significant superiority of BMC over CRT-P (6.607, 95% CI: 2.92, 10.29) in LVEF index and overall CRT-P (-13.946, 95% CI: -18.59, -9.29) and drug therapy (-4.176, 95% CI: -8.02, -.33) in LVES index. In addition, in terms of LVED index, the BMC had statistically significant differences with CRT-P (-10.187, 95% CI: -18.85, -1.52). BMC was also dominant to all methods in failure cases as a final outcome and the difference was statistically significant i.e. BMC vs CRT-D: 0.529 (0.45, 0.62) and BMC vs Drug: 0.516 (0.44, 0.60). In none of the outcomes, the other methods were statistically more efficacious than BMC. The BMC method was superior or similar to the other methods in all outcomes. Conclusion: The results of this study showed that the BMC method, in general, and especially in terms of failure cases index, had a higher level of clinical effectiveness. However, due to the lack of data asymmetry, insufficient data and head-to-head studies, BMC in this meta-analysis might be considered as an alternative to existing treatments for heart failure.

Effects of alpha lipoic acid and its derivative "andrographolid-lipoic acid-1" on ulcerative colitis: A systematic review with meta-analysis of animal studies.

We aimed to review and meta-analyze the inflammatory and oxidative factors following alpha lipoic acid (ALA) and its derivative "andrographolid-lipoic acid-1" (AL-1) in ulcerative colitis (UC). ALA plays an important role in scavenging intracellular radicals and inflammatory elements. AL-1 is found in herbal medicines with potent anti-inflammatory properties. Data were collected from the Google Scholar, PubMed, Scopus, Evidence-based medicine/clinical trials, and Cochrane library database until 2017, which finally resulted in 22 animal studies (70 rats and 162 mice). The beneficial effects of ALA or AL-1 on the most important parameters of UC were reviewed; also, studies were considered separately in mice and rats. Administration of ALA and AL-1 significantly reduced the tumor necrosis factor-α level compared with the controls, while data were not noteworthy in the meta-analysis (mean differences = -18.57 [95% CI = -42.65 to 5.51], P = 0.13). In spite of insignificant decrease in meta-analysis outcomes (differences = 6.92 [95% CI = -39.33 to 53.16], P = 0.77), a significant reduction in myeloperoxidase activity was shown following ALA or AL-1 treatment compared with the controls. Despite significant differences in each study, we had to exclude some studies to homogenize data for meta-analyzing as they showed insignificant results. Interleukin 6, cyclooxygenase-2, glutathione, malondialdehyde, superoxide dismutase, histopathological score, macroscopic and microscopic scores, disease activity index, body weight change, and colon length were also reviewed. Most studies have emphasized on significant positive effects of ALA and AL-1. Comprehensive clinical trials are obligatory to determine the precious position of ALA or AL-1 in the management of UC.

The efficacy of standard versus accelerated epi-off corneal cross-linking protocols: a systematic review and sub-group analysis.

PURPOSE: To compare the one-year efficacy of accelerated and standard 5.4 J/cm2 protocols of cross-linking (CXL) in the treatment of progressive keratoconus. METHODS: In this systematic review, two members of the research team searched Scopus, Pubmed, ISI, Ovid, Science Direct, and Cochrane databases independently for publications between January 2010 and December 2016. The majority of retrieved studies were not randomized clinical trials (RCT), or the second arm of the RCT was either untreated or customized CXL. The outcomes of interest were uncorrected distance visual acuity, corrected visual acuity, manifest refraction spherical equivalent, maximum keratometry in the central 3 mm, minimum keratometry in the central 3 mm, and corneal thickness in the apex or thinnest point at baseline and 1 year after CXL. RESULTS: Of the 453 papers found in the preliminary search, 23 papers were included in the final analysis. Analysis of variance of one-year changes showed that longer irradiation times were associated with a greater corneal flattening effect, although there was no difference in terms of improvement in vision or refraction. CONCLUSIONS: In other words, efficacy is comparable among different CXL protocols, so it is recommended to use the standard method in cases where maximum flattening is expected, such as young people and severe cases.

Effect of resveratrol on cognitive and memory performance and mood: A meta-analysis of 225 patients.

Resveratrol is a natural dietary phenolic compound which is extensively present in many edible fruits, including grape, berries, pomegranates, and peanuts. Reseveratrol has a broad spectrum of biological activities including anti-aging, chemopreventive, anti-carcinogenic, anti-inflammatory and antioxidant effects and thus it is effective in related diseases. Particularly, the positive effects of resveratrol in neuropsychological diseases have been proven in in-vitro and in-vivo studies. Some clinical trials have reported that resveratrol possesses preventive and therapeutic effects in cognitive disorders. Therefore, the current systematic review and meta-analysis aimed to assess the effects of resveratrol on cognition and memory performance as well as mood state. Electronic databases including Scopus, PubMed, Science Direct, and Cochrane library were searched with the keywords "Memory", "Cognitive", "Cognition" or "Mood" with "Resveratrol" until June 2017. Only clinical studies were included in this review. We have provided the most reliable evidence to date counting results obtained from 226 individuals from four randomized clinical trials evaluating the mentioned specific effects of resveratrol. The results of this meta-analysis showed that resveratrol has no significant effect on memory and cognitive performance assessed by auditory verbal learning tests. Two parameters of Profile of Mood States (POMS) including vigor and fatigue, decreased significantly by resveratrol. However, decrease in other parameters of POMS including tense/anxiety, depression, anger, and confusion by resveratrol was not significant. The key findings from this meta-analysis are that resveratrol has no significant impact on factors related to memory and cognitive performance, including learning ability, delayed recall, retention, and recognition with all effect sizes non-significant and effectively at zero. However, it has the potential to enhance mood. Further randomized, controlled trials are needed to achieve more conclusive results.

Efficacy and safety of interleukin-1 antagonists in rheumatoid arthritis: a systematic review and meta-analysis.

Rheumatoid arthritis patients have a high level of pro-inflammatory interleukin-1. Augmenting the blockade of interleukin-1 receptors by external interleukin-1 receptor antagonist modifies the progression of the disease. Therefore, the aim of this study was to evaluate the clinical efficacy and safety of interleukin-1 receptor antagonist (anakinra) in the treatment of rheumatoid arthritis. Clinical trials and extension studies that compared anakinra with placebo or other medications were included. Electronic bibliographic databases: PubMed, Scopus, and Web of Sciences were searched from inception to November 2017. The American College of Rheumatology 20% (ACR20) improvement was the primary efficacy outcome measure. Total number of adverse drug events, serious adverse drug events, total treatment withdrawals, and treatment-related withdrawals were safety outcome measures. Ten studies were included in this review. One study did not fulfil quantitative criteria and was assessed qualitatively. Six clinical trials and three extension studies were included in meta-analysis. Patients treated with anakinra are 42% more likely to have ACR20 response than patients without IL-1Ra (pooled RR 1.42; 95% CI 1.01, 2.00). Patients on 30-150 mg anakinra have lower Health Assessment Questionnaire (HAQ) score than patients without IL-1Ra (SMD - 0.28; 95% CI - 0.53, - 0.03). The inflammatory marker erythrocyte sedimentation rate (ESR) was significantly lower among patients treated with 30-150 mg anakinra (SMD - 0.44; 95% CI - 0.65, - 0.23). Patients on anakinra have a 34% more risk of treatment-related withdrawal than placebo. The other parameters were not found to be statistically significant. Anakinra has a significant improvement in ACR20, HAQ, and ESR. The ACR20 response is maintained after 48 weeks of treatment. Anakinra shows higher episodes of treatment-related withdrawals than placebo.

Does Evolocumab, as a PCSK9 Inhibitor, Ameliorate the Lipid Profile in Familial Hypercholesterolemia Patients? A Meta-Analysis of Randomized Controlled Trials.

Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a member of regulatory serine proteases which is mostly expressed in liver. In the physiological condition, LDL-C binds to LDL receptors (LDLRs) and via endocytosis, LDLRs are degraded. PCSK9 binds to the epidermal growth factor-like repeat A (EGFA) domain of extracellular LDLRs, and then physiological recycling of LDLRs from surface of liver is cancelled, resulting in elevation of circulating LDL-C in plasma. To evaluate whether evolucomab, as PCSK9 inhibitor monoclonal antibody, ameliorates lipid profile in familial hypercholesterolemia (FH) patients, this meta-analysis has been conducted. PubMed, Web of Science (ISI) and Scopus databases were searched for studies which had investigated the efficacy of evolucomab. Types of outcome investigated were percentage changes from baseline of the lipid profile. Our meta-analysis shows that evolucomab at the dosage of 420 mg monthly could decrease LDL-C  by 54.71%, TC by 35.08%, VLDL-C by 28.37 %, ratio of TC to HDL-C by 39.14 %, triglycerides by 12.11 %, and increased HDL-C by 6.06% from baseline compared to placebo at the end of study in FH patients. Our findings indicate that evolocumab could be a hopeful agent for challenging patients, such as statin intolerance or patients who fail to attain the target goal of LDL-C despite consumption of maximum doses of statins. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Rituximab as first choice for patients with refractory rheumatoid arthritis: cost-effectiveness analysis in Iran based on a systematic review and meta-analysis.

The aim of this study was to evaluate the effectiveness and cost-effectiveness of using rituximab as first line for patients with refractory rheumatoid arthritis in comparison with continuing conventional DMARDs, from a perspective of health service governors. A systematic review was implemented through searching PubMed, Scopus and Cochrane Library. Quality assessment was performed by Jadad scale. After meta-analysis of ACR index results, QALY gain was calculated through mapping ACR index to HAQ and utility index. To measure the direct and indirect medical costs, a set of interviews with patients were applied. Thirty-two patients were selected from three referral rheumatology clinics in Tehran with definite diagnosis of refractory rheumatoid arthritis in the year before and treatment regimen of either rituximab or DMARDs within last year. Incremental cost-effectiveness ratio was calculated for base case and scenario of generic rituximab. Threefold of GDP per capita was considered as threshold of cost-effectiveness. Four studies were eligible to be considered in this systematic review. Total risk differences of 0.3 for achieving ACR20 criteria, 0.21 for ACR50 and 0.1 for ACR70 were calculated. Also mean of total medical costs of patients for 24 weeks were $3985 in rituximab group and $932 for DMARDs group. Thus, the incremental cost per QALY ratio will be $45,900-$70,223 in base case and $32,386-$49,550 for generic scenario. Rituximab for treatment of patients with refractory rheumatoid arthritis is not considered as cost-effective in Iran in none of the scenarios.

Is Taurolidine-citrate an effective and cost-effective hemodialysis catheter lock solution? A systematic review and cost- effectiveness analysis.

BACKGROUND: Prevention of catheter-related infection is of prime importance,. However, because of the risks caused by the leakage of circulating antibiotics and development of resistance to antibiotics, they are replaced by lock solutions. The aim of this study was to evaluate the efficacy and cost- effectiveness of taurolidine-citrate as a hemodialysis catheter lock solution compared to other common alternatives in Iran. METHODS: To evaluate the efficacy of taurolidine-citrate, a systematic review was conducted by searching electronic databases. The outcomes of interest for cost-effectiveness analysis were as follows: "Catheter-related bacteremia episodes"; "catheter-related bacteremia-free survival"; "catheter thrombosis rate" for efficacy evaluation and "reduction of catheter-related infection". For evidence synthesis, a meta-analysis was conducted on the extracted efficacy data. To evaluate the cost of treatments, direct medical costs were included, and the incremental cost-effectiveness ratio was calculated for each comparison. The payers' (patients and insurance companies) perspectives were used for cost analysis. RESULTS: After carrying out the systematic process, three articles were included in the analysis. Considering 95% confidence interval, the relative difference was -0.16 (-0.25 to -0.07) for catheterrelated bacteremia episode, indicating that the rate of catheter-related infections in hemodialysis patients who used taurolidine-citrate was 16% less than in those hemodialysis patients who received heparin. Considering 95% confidence interval, the relative difference was 0.13 (-0.06 0.32) for catheter thrombosis, showing that the rate of catheter-related thrombosis in hemodialysis patients who used taurolidine-citrate was 13% more than in hemodialysis patients who received heparin. The results of this analysis indicated that taurolidine-citrate, compared to heparin, was more effective in preventing catheter-related infection; therefore, it could be considered as a superior strategy. Nevertheless, compared to heparin-gentamicin combination, taurolidine-citrate is an inferior strategy because of its higher cost and lower infection prevention. CONCLUSION: Compared to heparin, taurolidine-citrate is a superior option, but it is an inferior strategy compared to heparin-gentamicin combination. The clinical evidences on taurolidine-citrate, heparin and gentamicin/heparin are not sufficient for making confident decisions.

Influence of ascorbic acid supplementation on type 2 diabetes mellitus in observational and randomized controlled trials; a systematic review with meta-analysis.

PURPOSE: There are controversial data regarding the beneficial effects of ascorbic acid (AA) supplementation in type 2 diabetes mellitus (T2DM). In this systematic review, we aimed to criticize the current relevant data from both observational and randomized controlled trials (RCTs). METHODS: All observational and RCTs conducted to assess anti-hyperglycemic effects of AA in diabetics, published before January 2013, were included. To obtain all related studies Google Scholar, PubMed, Scopus, IranMedex, and Magiran web databases were searched. Exclusion criteria were animal studies, and studies conducted in Type 1 DM, children or pregnant women. Main outcome measures were fasting blood sugar (FBS), and glycated hemoglobin (HbA1c). According to degree of heterogeneity, fixed or random effect models were employed. Meta-analyses were done using Stats Direct software, version 3.0.97. The quality of included articles and publication bias were also assessed. RESULTS: We selected 38 articles; 26 observational studies and 12 RCTs. Due to severe methodological heterogeneity in all observational studies and some of RCTs, we could pool data from only 5 RCTs in a meta-analysis. Single intake of AA versus placebo showed a significant effect on FBS; with the standardized mean difference (SMD): -20.59, 95% confidence intervals (95% CI): -40.77 to -0.4 (p= 0.04), but non-significant effect on HbA1c; SMD: -0.46, 95% CI: -1.75 to 0.84 (p= 0.4). Effect of other antioxidants with/without AA supplementation on FBSwere nonsignificant; SMD: -4.26 (p= 0.8), and SMD: -12.04 (p= 0.3), respectively. Also, their effect on HbA1c was non-significant; SMD: 0.53 (p= 0.11), and SMD: 0.28 (p= 0.34), respectively. CONCLUSIONS: Our study supports the positive effect of AA in reduction of FBS in diabetics, however, due to insufficient evidence ragarding long term safety of AA supplementation and limited number of RCTs, the long term use of this vitamin for its anti-diabetic properties cannot be strongly recommended.

Commercialization of biopharmaceutical knowledge in Iran; challenges and solutions.

BACKGROUND: The objective of this study was to investigate the application of the university research findings or commercialization of the biopharmaceutical knowledge in Iran and determine the challenges and propose some solutions. RESULTS: A qualitative study including 19 in-depth interviews with experts was performed in 2011 and early 2012. National Innovation System (NIS) model was employed as the study design. Thematic method was applied for the analysis. The results demonstrate that policy making, regulations and management development are considered as fundamental reasons for current commercialization practice pattern. It is suggested to establish foundation for higher level documents that would involve relating bodies and provide them operational guidelines for the implementation of commercialization incentives. CONCLUSIONS: Policy, regulations and management as the most influential issue should be considered for successful commercialization. The present study, for the first time, attempts to disclose the importance of evidence input for measures in order to facilitate the commercialization process by the authorities in Iran. Overall, the NIS model should be considered and utilized as one of the effective solutions for commercialization.

A system dynamics model for national drug policy.

BACKGROUND: Data modeling techniques can create a virtual world to analyze decision systems. National drug authorities can use such techniques to take care of their deficiencies in decision making processes. This study was designed to build a system dynamics model to simulate the effects of market mix variables (5 P's) on the national drug policy (NDP) indicators including availability, affordability, quality, and rationality. This was aimed to investigate how to increase the rationality of decision making, evaluate different alternatives, reduce the costs and identify the system obstacles.System dynamics is a computer-based approach for analyzing and designing complex systems over time. In this study the cognitive casualty map was developed to make a concept about the system then the stock-flow model was set up based on the market demand and supply concept. RESULTS: The model demonstrates the interdependencies between the NDP variables through four cognitive maps. Some issues in availability, willingness to pay, rational use and quality of medicines are pointed in the model. The stock-flow diagram shows how the demand for a medicine is formed and how it is responded through NDP objectives. The effects of changing variables on the other NDP variables can be studied after running the stock-flow model. CONCLUSION: The model can initiate a fundamental structure for analyzing NDP. The conceptual model made a cognitive map to show many causes' and effects' trees and reveals some relations between NDP variables that are usually forgotten in the medicines affairs. The model also provides an opportunity to be expanded with more details on a specific disease for better policy making about medication.

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.

Pharmacokinetic considerations for drugs that treat diarrhea-predominant irritable bowel syndrome: what's new?

INTRODUCTION: Irritable bowel syndrome (IBS), which presents a significant healthcare and socioeconomic burden, is one of the main issues in the field of therapy. Hence, it is imperative to tackle this matter by evaluating the safety and efficacy of the available treatments and determining the ideal approach for each patient. AREAS COVERED: We reviewed the pharmacokinetics and safety of pharmacologic interventions administered in diarrhea-predominant IBS (IBS-D) patients. PubMed, Google Scholar and the USFDA databases were searched up to November 2023 to include all updated information on eluxadoline, alosetron, and rifaximin. EXPERT OPINION: The most effective way to treat IBS-D is to focus on managing the most common symptoms. However, healthcare providers face a challenge when it comes to identifying the right treatment for each patient, and the root cause of this is the diversity of IBS-D population. Studies have shown that there are differences in how men and women metabolize drugs, which may lead to gender-specific adverse reactions. Women tend to have higher drug concentrations in their bloodstream and take longer to eliminate them. Therefore, healthcare providers may need to reduce the dosage for female patients. Integrating IBS care into sustainable development efforts can indirectly contribute to achieving SDGs and promote health and well-being for all.

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.