Background: Research has indicated that calcitonin gene-related peptide (CGRP) receptor antagonists can be effective in the acute treatment of migraine. Six major drugs are included within this category: telcagepant, olcegepant, BI 44370, rimegepant (BMS-927711), MK3207, and ubrogepant. However, no previous studies have performed network meta-analyses to directly compare the effects of these drugs. In the present study, we assessed the therapeutic qualities of these six different drugs to inform further clinical research. Methods: We searched PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register for Controlled Trials for relevant randomized controlled trials (RCTs) published through to October 2018. Two reviewers performed a network meta-analysis of efficacy and toxicity on the basis of odds ratios (ORs). Results: Ten randomized controlled trials involving 8,174 patients were included in our analysis. Olcegepant (OR: 4.09; CI: 1.81, 9.25), ubrogepant (OR: 2.11; CI: 1.10, 4.05), and BI 44370 (OR: 3.36; CI: 2.24, 5.04) were more effective in ensuring pain relief 2 h after treatment than was placebo treatment. BI 44370 was associated with an increased risk of adverse events when compared with placebo treatment (OR: 1.57; CI: 1.32, 1.88). Surface under the cumulative ranking curve analysis revealed that olcegepant was most effective and ubrogepant was associated with the lowest risk of adverse events among the six treatment options. Conclusion: Olcegepant was more effective, and ubrogepant had lower toxicity than the remaining treatments. CGRP antagonists are promising for the acute treatment of migraine, especially among patients who are unable to take triptans.

Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs). Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the "gemtc 0.8-7" and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes. Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: -1.547; 95% CrI: -2.473 to -0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis. Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.

Background: Antithrombotic treatment, including low molecular weight heparin (LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality. Methods: We performed a systematic review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS). Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14-3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, -3.87, 5.83 days). Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding. Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955.

A typical antipsychotics for neuropsychiatric symptoms in dementia have been tested in much larger trials than the older conventional drugs. The advantage of larger sample sizes is that negative findings become less likely and the effect estimates more precise. However, as sample sizes increase, the trials also get more expensive and time consuming while exposing more patients to drugs with unknown safety profiles. Moreover, a large sample size might yield a statistically significant effect that is not necessarily clinically relevant.

Wound management is a significant and growing issue worldwide. Knowledge of dressing products and clinical expertise in dressing selection are two major components in holistic wound management to ensure evidence-based wound care. With expanding global market of dressing products, there is need to update clinician knowledge of dressing properties in wound care. Optimal wound management depends on accurate patient assessment, wound diagnosis, clinicians' knowledge of the wound healing process and properties of wound dressings. We conducted a comprehensive review of the physical properties of wound dressing products, including the advantages and disadvantages, indications and contraindications and effectiveness of first-line interactive/bioactive dressing groups commonly used in clinical practice. These include semipermeable films, foams, hydroactives, alginates, hydrofibers, hydrocolloids, and hydrogels. In making decisions regarding dressing product selection, clinicians need to ensure a holistic assessment of patient and wound etiology, and understand dressing properties when making clinical decisions using wound management guidelines to ensure optimal patient outcomes. This review has highlighted there is lack of high quality evidence and the need for future well designed trials.

As a traditional Chinese medicine (TCM) prescription for acute stroke, Liangxue Tongyu formula (LXTYF) was widely used as auxiliary treatment measure in some clinical practice. This study aimed to evaluate the clinical efficacy and safety of LXTYF combined western conventional medicine (WCM) with WCM only for acute intracerebral hemorrhage (ICH).

Objective: To explore the treatment effect of statins used together with clopidogrel on cerebral infarction (CI). Methods: One hundred and thirty non-clopidogrel resistant patients were divided into a dynamic clopidogrel resistant (DCR) group and a continuous Non clopidogrel resistance (NCR) group. Patients were randomly assigned to AC group (atorvastatin 40 mg/d + clopidogrel, 51 patients) and RC group (rosuvastatin 20 mg/d + clopidogrel, 47 patients). The patient's platelet aggregation rate (PAR) was measured on visit 0 (baseline), visit 1 (1 week after clopidogrel alone treatment), and visits 2 to 4 (one, three, and 6 months after clopidogrel plus statins treatment). The platelet reactivity index (PRI) was assessed on visits 0, 2, and 4, and clopidogrel thiol metabolite (H4) levels was measured on visits 2 and 4. DNA sequencing was used to determine CYP3A4, CYP2C9, and CYP2C19 genotypes in all patients. Results: PAR, PRI, and H4 levels, DCR ratio, and the genotype frequencies of CYP2C9*3εC, CYP2C19*2εA, and CYP2C19*3εA of both groups were similar (p > 0.05). CYP2C19εA *2 and *3 were independent risk factors for DCR (p < 0.05). Conclusion: Clopidogrel combined with atorvastatin does not affect platelet inhibition and does not increase the incidence of DCR. The incidence of DCR in the Chinese population is high and is related to CYP2C19εA.

Background: Antipsychotic drugs may lead to side effects such as obesity, diabetes, dyslipidemia, and cardiovascular disease. The current systematic review and network meta-analysis analyzes and provides an update on the clinical performance of these add-ons in comparison to placebo on body weight and body mass index (BMI) reductions. Methods: A comprehensive literature search was performed on electronic databases: PubMed (1946-), Embase (1974-), Cochrane library (1992-), and OpenGrey (2000-) until 31 July 2018. Network meta-analyses, comparing the body weight change, BMI change and withdrawn due to adverse events of different pharmacological add-ons, was performed using a multivariate meta-regression model with random-effects, adopting a frequentist approach. To rank the prognosis for all add-ons, we used surface under the cumulative ranking (SUCRA) values. Outcomes: From 614 potential studies identified, 27 eligible studies (n = 1,349 subjects) were included. All the studies demonstrated low to moderate risk of bias. For the analysis of body weight change, all add-ons except Ranitidine showed significant weight reductions comparing to placebo. The effectiveness rank based on SUCRA results from highest to lowest was Sibutramine, Topiramate, Metformin, Reboxetine, Ranitidine, and placebo. A similar pattern was seen for BMI change. The analysis of safety outcome did not detect significantly increased withdrawn number from the add-ons. Current evidence showed relatively good tolerance and safety of using the pharmacological add-ons. Interpretation: Topiramate and Metformin are effective add-on treatments in controlling antipsychotic-induced weight gain, comparing to placebo. They are well tolerated in short-term period. Although Sibutramine has the highest rank of the effectiveness, its license has been withdrawn in many countries due to its adverse effects. Hence, Sibutramine should not be adopted to treat antipsychotic-induced weight gain.

Background: It is estimated that one in five people worldwide faces a diagnosis of a malignant neoplasm during their lifetime. Carvacrol and its isomer, thymol, are natural compounds that act against several diseases, including cancer. Thus, this systematic review aimed to examine and synthesize the knowledge on the antitumor effects of carvacrol and thymol. Methods: A systematic literature search was carried out in the PubMed, Web of Science, Scopus and Lilacs databases in April 2020 (updated in March 2021) based on the PRISMA 2020 guidelines. The following combination of health descriptors, MeSH terms and their synonyms were used: carvacrol, thymol, antitumor, antineoplastic, anticancer, cytotoxicity, apoptosis, cell proliferation, in vitro and in vivo. To assess the risk of bias in in vivo studies, the SYRCLE Risk of Bias tool was used, and for in vitro studies, a modified version was used. Results: A total of 1,170 records were identified, with 77 meeting the established criteria. The studies were published between 2003 and 2021, with 69 being in vitro and 10 in vivo. Forty-three used carvacrol, 19 thymol, and 15 studies tested both monoterpenes. It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity, and also displayed different antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR). Conclusions: Carvacrol and thymol exhibited antitumor and antiproliferative activity through several signaling pathways. In vitro, carvacrol appears to be more potent than thymol. However, further in vivo studies with robust methodology are required to define a standard and safe dose, determine their toxic or side effects, and clarify its exact mechanisms of action. This systematic review was registered in the PROSPERO database (CRD42020176736) and the protocol is available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176736.

Practical adherence barriers (e.g., medication frequency) are generally more amenable to intervention than perceptual barriers (e.g., beliefs). Measures which assess adherence barriers exist, however these tend to measure a mix of factors. There is a need to identify what practical barriers are captured by current measures.

Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion.

Background: During the last decades, a huge body of evidence has been accumulated suggesting that Citrus fruits and their juices might have a role in preventing many diseases including cancer. Objective: To summarize the numerous evidences on the potential of Citrus juices and their extracts as anticancer agents. Data sources: A systematic review of articles written in English using MEDLINE (1946-present), EMBASE (1974-present) and Web of Sciences (1970-present) was performed independently by two reviewers. Search terms included Citrus, Citrus aurantifolia, Citrus sinensis, Citrus paradisi, Citrus fruits, Citrus fruits extract, cancer, neoplasm, neoplasia, tumor, metastasis, carcinogenesis, proliferation. The last search was performed on March 16th, 2017. Study selection: Study selection and systematic review were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Prior to the beginning of the review, Authors defined a checklist for inclusion criteria, thus including articles which meet the following: (i) published on peer-reviewed scientific journals; (ii) Citrus juice used alone; (iii) extracts derived from Citrus juice; (iii) for preclinical studies, an exposure time to Citrus juices and their extracts more than 24 h. Reviews, meta-analyses, conference abstracts and book chapters were excluded. Data extraction: Three reviewers independently performed the extraction of articles. Data synthesis: 22 papers met our inclusion criteria and were eligible for inclusion in the final review. According to the kind of study, the selected ones were further divided in preclinical (n = 20) and observational (n = 2) studies. Conclusion: The studies discussed in this review strongly corroborate the role of Citrus juices and their derivatives as potential resource against cancer.

Background: A tibia shaft fracture is one of the most common long bone fractures, with two general types, open fracture and close fracture. However, there is no universally accepted guideline suggesting which treatment to use under certain circumstances. Therefore, a comprehensive network meta-analysis (NMA) is needed to summarize existing studies and to provide more credible data-based medical guidelines. Methods: Available literature was identified by searching medical databases with relevant key terms. Studies that met the inclusion and exclusion criteria, baseline, intervention, and the outcome of treatments, were extracted. A comparative connection of these studies was demonstrated through net plots. Continuous variables and binary variables were reported as mean difference (MD) and odds ratio (OR) with a 95% credible interval (CrI), respectively. The comparison of direct and indirect outcome and their P-value were listed in the node-splitting table. Treatments for each endpoint were ranked by their surface under the cumulative ranking curve (SUCRA) value. A heat plot was created to illustrate the contribution of raw data and the inconsistency between direct and indirect comparisons. Results: According to the search strategy, 697 publications were identified, and 25 records were included, involving 3,032 patients with tibia shaft fractures. Seven common surgical or non-surgical treatments, including reamed intramedullary nailing (RIN), un-reamed intramedullary nailing (UIN), minimally reamed intramedullary nailing (MIN), ender nailing (EN), external fixation (EF), plate, and cast, were compared, in terms of time to union, reoperation, non-union, malunion, infection and implant failure. Plate performed relatively better for time to union, while cast might be the best choice in close cases to reduce the risks of reoperation, non-union, malunion, and infection. To prevent implant failure, EN seemed to be better. Conclusion: Cast might have the highest probability of the most optimal choice for tibia shaft fracture in close cases, while reamed intramedullary nailing ranked second.

We conducted a systematic review and meta-analysis to determine the effectiveness and safety of anti-tumor necrosis factor-alpha (TNF-α) agents in the treatment of Behcets' disease (BD)-associated uveitis.

Objective: The purpose of this meta-analysis of longitudinal studies is to determine the safety and efficacy of artesunate combined with other forms of adjunctive therapies for severe malaria. Methods: Following the PRISMA guidelines, we searched multiple databases with the search terms "artesunate" and "adjunctive therapy" and "severe malaria" in July 2020. If the search showed a randomized controlled trial, the study was included in this meta-analysis. The random-effects model was used to calculate the combined incidence rate and relative risk or risk difference. Results: This meta-analysis included nine longitudinal studies with 724 participants. We found that the mortality rates in the artesunate monotherapy group and the artesunate + adjuvant therapy group are similar (RD = -0.02, 95% confidence interval: -0.06-0.02). The incidence of adverse reactions in the artesunate monotherapy group and the artesunate + adjuvant therapy group was also similar. Conclusion: No significant differences in safety and efficacy were observed between the artesunate monotherapy group and the artesunate + adjuvant therapy group. Higher quality and rigorously designed randomized controlled studies are needed to validate our findings.

The dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin has been found to reduce progressive albuminuria, but the exact mechanism of inhibition is unclear. Podocyte epithelial-to-mesenchymal transition (EMT) has emerged as a potential pathway leading to proteinuria in diabetic nephropathy (DN). Stromal cell-derived factor-1α (SDF-1α), one of the substrates of DPP-4, can activate the protein kinase A pathway and subsequently inhibit its downstream effector, transforming growth factor-β1 (TGF-β1), which induces podocyte EMT. Thus, this study was designed to test the hypothesis that saxagliptin reduces progressive albuminuria by preventing podocyte EMT through inhibition of SDF-1α cleavage in DN. The results of a series of assays, including ELISA, western blotting, and immunochemistry/immunofluorescence, showed that saxagliptin treatment obviously ameliorated urinary microalbumin excretion and renal histological changes in high-fat diet/streptozotocin-induced diabetic rats. Furthermore, saxagliptin-treated diabetic rats presented with suppression of DPP-4 activity/protein expression accompanied by restoration of SDF-1α levels, which subsequently hindered NOX2 expression and podocyte EMT. In vitro, we consistently observed that saxagliptin significantly inhibited increased DPP-4 activity/expression, oxidative stress and podocyte EMT. Application of an SDF-1α receptor inhibitor (AMD3100) to cultured podocytes further confirmed the essential role of SDF-1α in podocyte EMT inhibition. In sum, we demonstrated for the first time that saxagliptin treatment plays an essential role in ameliorating progressive DN by preventing podocyte EMT through a SDF-1α-related pathway, suggesting that saxagliptin could offer renoprotection and that SDF-1α might be a potential therapeutic target for DN.

Background: Dementia is a global health concern, causing serious health and socioeconomic burdens with population aging. The associated symptoms of dementia, called behavioral and psychological symptoms of dementia (BPSD), are factors contributing to the socioeconomic burden of dementia. Recently, herbal medicine (HM) has attracted attention as a potential complementary therapy for BPSD. Therefore, this systematic review was aimed at analyzing the effectiveness (or efficacy), safety, and research status of HM in BPSD management through a comprehensive review. Methods: Thirteen electronic databases were searched comprehensively. Related clinical studies published until December 28, 2020, were collected. The methodological quality was evaluated using tools such as the Cochrane Collaboration's risk of bias tool according to the study design. The effectiveness (or efficacy) was analyzed for randomized controlled trials (RCTs) only, and when sufficient homogeneity was assured, effect estimates were presented as mean difference (MD) and risk ratio (RR), with 95% confidence interval (CIs), through a meta-analysis. Results: A total of 52 clinical studies, including 36 RCTs, were included in this review. As an adjunctive therapy, HM showed statistically significant benefits in BPSD severity assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (combined with psychotropic drugs: MD = -3.48, 95% CI: -3.96 to -2.99; with anti-dementia drugs: MD = -2.81, 95% CI: -3.17 to -2.45) and Neuropsychiatric Inventory (with anti-dementia drugs: MD = -3.23, 95% CI: -4.06 to -2.40). Adverse events were significantly less frequent in the HM group (RR = 0.50; 95% CI: 0.28 to 0.88). However, the methodological quality of the RCTs included in this systematic review was not optimal overall. Conclusion: According to the findings of this review, HM may be associated with additional benefits in BPSD treatment, particularly when used as an adjunct to conventional medications, including psychotropic and anti-dementia drugs. However, considering the methodological quality of the included RCTs, this clinical evidence is not robust. Nevertheless, dementia is a global health concern, and considering the limitations of conventional psychotropic drugs for BPSD, a major cause of the disease burden, HM appears to be a promising complementary therapy that warrants further research.

With a rapidly aging population, the prevalence of hypertension in adults continues to rise, placing a substantial and escalating social and economic burden. Ilex hainanensis Merr. is commonly used as a folk remedy for treating hypertension, dyslipidemia, and inflammation in China. This systematic review aims to evaluate current evidence for the therapeutic effect of Ilex hainanensis Merr. extract (EIH) on essential hypertension. Six electronic databases (Pubmed, MEDLINE, The Cochrane Central Register of Controlled Trials, Chinese Scientific Journals Database, Wanfang and CNKI) were searched to identify eligible randomized controlled trials (RCTs) relevant to EIH on essential hypertension up to Jan 2018. Six RCTs including 772 participants met eligibility criteria. Methodological quality of the trials was generally low. Meta-analysis showed that EIH demonstrated a beneficial effect for lowering systolic and diastolic blood pressure (SBP/DBP), left ventricular mass (LVM) in participants with essential hypertension. There was no significant difference between EIH and antihypertensive drugs in SBP (WMD: -0.44 [-2.30, 1.43]; P = 0.65), DBP (WMD: WMD: -0.02 [-1.13, 1.09]; P = 0.98) and LVM (WMD: -1.36 [-4.99, 2.26]; P = 0.46). Moreover, one trial showed that EIH combined with antihypertensive drugs was more effective in lowering blood pressure than those antihypertensive drugs used alone. However, the findings were limited by the small sample sizes, duration and low methodological quality of the trials. This is the first systematic review of EIH on essential hypertension. More rigorous RCTs with high quality are still needed to prove the effectiveness and safety of EIH and its preparations for essential hypertension.

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4-15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: -18.05, 95% CI (-25.51, -10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (-32.80, -14.18), P < 0.00001], 7day [MD: -33.01, 95% CI (-37.31, -28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: -1.91, 95% CI (-2.06, -1.75), P < 0.00001], as well as the duration of phototherapy [MD: -0.64, 95% CI (-0.84, -0.44), P < 0.00001] and hospitalization [MD: -2.68, 95% CI (-3.18, -2.17), P < 0.00001], when compared with the control group. Additionally, no serious adverse reaction was reported. Conclusion: This meta-analysis shows that probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice.

The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000-2,000,000 compounds per screening campaign), before pre-clinical trials to select optimum lead. Carrying out in vitro screening of antimalarials is very difficult as different assay methods are subject to numerous sources of variability across different laboratories around the globe. Despite this, in vitro screening is an essential part of antimalarial drug development as it enables to resource various confounding factors such as host immune response and drug-drug interaction. Therefore, in this article, we try to illustrate the basic necessity behind in vitro study and how new methods are developed and subsequently adopted for high-throughput antimalarial drug screening and its application in achieving the next level of in vitro screening based on the current approaches (such as stem cells).