Analysis Of Clinical Trials Research Articles

Top 100 most-cited clinical trials and systematic reviews related to children and adolescents’ oral health

Aim: To identify and analyze the 100 most-cited clinical trials (CTs) and systematic reviews (SRs) related to children and adolescents’ oral health. Methods: A search was conducted in the Web of Science Core Collection (WoS-CC), using a specific search strategy. Papers were ranked in descending order, considering number of citations. Only CTs and SRs were considered. Two reviewers selected the papers and collected the bibliometric data: year of publication; number and density of citations; study designs; journals; authors; countries and institutions; topics of study; and keywords. Poisson regression was performed to verify associations between the number of citations and bibliometric parameters. Results: The 100 most-cited papers were published between 1982 and 2018 and received a total of 8,702 citations in the WoS-CC (ranging from 52 to 177). Fifty-three papers were CTs and 47 SRs. The American Journal of Orthodontics and Dentofacial Orthopedics published the most papers (n=20). Twetman S contributed the highest number of papers (n=7). The United States of America was the most prolific country (n = 17), followed by the Netherlands (n=11). The University of Nijmegen (Netherlands) presented 8 papers among the most-cited. The main topic of interest was Cariology (n = 40). “Dental Caries” was the most frequent keyword (n = 20). The citations’ number from WoS-CC decreased by 1.3% each year (RP: 0.987, 95%CI: 0.975–1.000, p = 0.048). Conclusion: This bibliometric study allowed an analysis of the most-cited CTs and SRs related to children and adolescents’ oral health, highlighting the most prolific authors, institutions and countries based on the number of citations.

Neuroprotective Drug Discovery From Phytochemicals and Metabolites for CNS Viral Infection: A Systems Biology Approach With Clinical and Imaging Validation.

BackgroundRecent studies have reported that pulmo-neurotropic viruses can cause systemic invasion leading to acute respiratory failure and neuroinfection. The tetracycline class of secondary metabolites of microorganisms is effective against several migrating neurotropic viral disorders, as Japanese-Encephalitis (JE), Severe-Acute-Respiratory-Syndrome Coronavirus-2 (SARS-COV2), Human-Immunodeficiency-Virus (HIV), and Simian-Immunodeficiency-Virus (SIV). Another microbial secondary metabolite, cephalosporin, can be used for anti-viral combination therapy. However, a substantial public health debacle is viral resistance to such antibiotics, and, thus, one needs to explore the antiviral efficiency of other secondary metabolites, as phytochemicals. Hence, here, we investigate phytochemicals like podophyllotoxin, chlorogenic acid, naringenin, and quercetin for therapeutic efficiency in neurotropic viral infections.MethodsTo investigate the possibility of the afferent neural pathway of migrating virus in man, MRI scanning was performed on human subjects, whereby the connections between cranial nerves and the brain-stem/limbic-region were assessed by fiber-tractography. Moreover, human clinical-trial assessment (n = 140, p = 0.028) was done for formulating a quantitative model of antiviral pharmacological intervention. Furthermore, docking studies were performed to identify the binding affinity of phytochemicals toward antiviral targets as (i) host receptor [Angiotensin-converting Enzyme-2], (ii) main protease of SARS-COV2 virus (iii) NS3-Helicase/Nucleoside triphosphatase of Japanese-encephalitis-virus, and the affinities were compared to standard tetracycline and cephalosporin antibiotics. Then, network pharmacology analysis was utilized to identify the possible mechanism of action of those phytochemicals.ResultsHuman MRI-tractography analysis showed fiber connectivity, as: (a) Path-1: From the olfactory nerve to the limbic region (2) Path-2: From the peripheral glossopharyngeal nerve and vagus nerves to the midbrain-respiratory-center. Docking studies revealed comparable binding affinity of phytochemicals, tetracycline, and cephalosporin antibiotics toward both (a) virus receptors, (b) host cell receptors where virus-receptor binds. The phytochemicals effectively countered the cytokine storm-induced neuroinflammation, a critical pathogenic pathway. We also found that a systems-biology-based double-hit mathematical bi-exponential model accounts for patient survival-curve under antiviral treatment, thus furnishing a quantitative-clinical framework of secondary metabolite action on virus and host cells.ConclusionDue to the current viral resistance to antibiotics, we identified novel phytochemicals that can have clinical therapeutic application to neurotropic virus infection. Based on human MRI scanning and clinical-trial analysis, we demarcated the anatomical pathway and systems-biology-based quantitative formulation of the mechanism of antiviral action.

Analysis of female enrollment in clinical trials for alcohol and substance use disorders: Is it time for sex-informed pharmacotherapy?

BackgroundWomen represent an increasing number of individuals with alcohol and substance use disorders (ASUDs), and sex-differences might affect results of interventional clinical trials (CTs). We aim at assessing the proportion of women and the reporting of sex-stratified and female-specific data in CTs for ASUDs. MethodsWe extracted data from ClinicalTrials.gov on Phase 1–3 CTs of investigational drugs for ASUDs conducted from 2000 to 2021 and identified articles related to these trials. We determined the average proportions of women enrolled per trial overall, over time, and by disease area and trial phase. Next, we calculated the proportion of articles reporting sex-stratified and female-specific data. ResultsIn the 234 CTs identified, the overall proportion of women was 33.4% [95% CI: 32.7%-33.9%]), with an increasing temporal trend. Women's participation was higher in CTs of investigational drugs for tobacco (43.5% [95% CI: 42.4% -44.5%]) and alcohol use disorder (35.9% [95% CI: 34.54%–37.21%]), and closely mirrored their representation in the disease populations (46% and 37%). Conversely, women were underrepresented in clinical trials of drugs for cocaine and stimulant use disorders (25.8% [95% CI: 24.6%–27.1%]) and opioid use disorders (25.9% [95% CI:24.2%–27.7%]). Nine publications reported sex-stratified data in the method and/or result section, whereas none documented female-specific data. ConclusionsEnrollment of women in ASUDs CTs has increased over time but remains low in several disease areas. This, together with the low rates of reporting of sex-stratified data, calls for an adequate inclusion of sex in the design and analysis of CTs for ASUDs.

Systematic Data Monitoring and Analysis of Cardiovascular Off-label Prescriptions in Pediatrics: Focus on Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Beta Blockers.

Many efforts have been made to stimulate clinical trials (CTs) in pediatrics but most of the drugs are still authorized only in adults and used off-label in the pediatric population. To assess how widespread is the off-label prescription in Italy and to identify areas of unmet medical need by applying a model for the systematic collection and analysis of data. A study was performed using 2015 data from the Italian Medicines Utilization Monitoring Centre Health Database (OsMed). A study sample of 3,726,583 pediatric patients, was considered. Cardiovascular drugs were selected for this study. Assessment of the off-label use, the analysis of the pharmacovigilance signals, a bibliographic research and the analysis of ongoing CTs were carried out. In 2015, 8,544 pediatric patients received treatment with a cardiovascular drug. Angiotensin converting enzyme inhibitors (ACE-I) followed by betablockers agents are the most prescribed molecules. Eight molecules were selected and an in-depth analysis conducted. The PhV network showed only one record of adverse reaction as off-label in 2015. The results show several therapeutic areas of use in pediatrics. Off-label in pediatrics is largely widespread in Europe and US and our results show it is also present in Italy. Molecules selected are used off-label for therapeutic areas such as oncologic, hematological and rare diseases. Results of pharmacovigilance suggests underreporting. The analysis carried out in this study could be an open track for a systematic monitoring activity and of interest for prescribers, pediatricians and other healthcare professionals during the clinical practice.

In Silico Model Estimates the Clinical Trial Outcome of Cancer Vaccines.

Over 30 years after the first cancer vaccine clinical trial (CT), scientists still search the missing link between immunogenicity and clinical responses. A predictor able to estimate the outcome of cancer vaccine CTs would greatly benefit vaccine development. Published results of 94 CTs with 64 therapeutic vaccines were collected. We found that preselection of CT subjects based on a single matching HLA allele does not increase immune response rates (IRR) compared with non-preselected CTs (median 60% vs. 57%, p = 0.4490). A representative in silico model population (MP) comprising HLA-genotyped subjects was used to retrospectively calculate in silico IRRs of CTs based on the percentage of MP-subjects having epitope(s) predicted to bind ≥ 1–4 autologous HLA allele(s). We found that in vitro measured IRRs correlated with the frequency of predicted multiple autologous allele-binding epitopes (AUC 0.63–0.79). Subgroup analysis of multi-antigen targeting vaccine CTs revealed correlation between clinical response rates (CRRs) and predicted multi-epitope IRRs when HLA threshold was ≥ 3 (r = 0.7463, p = 0.0004) but not for single HLA allele-binding epitopes (r = 0.2865, p = 0.2491). Our results suggest that CRR depends on the induction of broad T-cell responses and both IRR and CRR can be predicted when epitopes binding to multiple autologous HLAs are considered.

Prebióticos e probióticos na saúde e no tratamento de doenças intestinais: uma revisão integrativa

Objetivo: realizar uma revisão integrativa sobre a função dos prebióticos e probióticos na manutenção da saúde, bem como suas aplicações no tratamento da constipação idiopática crônica (CIC), da síndrome do intestino irritável (SII) e da doença inflamatória intestinal (DII). Metodologia: trata-se de uma revisão integrativa da literatura, cuja busca dos estudos foi realizada nas bases de dados Cochrane e PubMed, com análise de trabalhos publicados nos últimos dez anos (2010-2020) escritos em inglês. Resultados: O uso de probióticos na CIC e SII mostrou efeitos benéficos na redução dos sintomas dessas doenças, modificação na microbiota e melhora na qualidade de vida dos pacientes. Na CIC, a inulina foi o prebiótico com mais efeitos positivos na sintomatologia da doença. Na DII, o uso de prebióticos e probióticos mostrou efeitos benéficos discretamente maiores para a RCU do que para a DC. Conclusão: Prebióticos e probióticos podem trazer tanto benefícios preventivos quanto terapêuticos à saúde intestinal, com ações diretas e indiretas na microbiota, imunidade e processos metabólicos do hospedeiro. A utilização desses compostos e microrganismos nas doenças estudadas demonstram resultados promitentes, principalmente, no campo dos probióticos. A partir da análise dos ensaios clínicos, as cepas promissoras no tratamento da DII foram Bifidobacterium, Lactobacillus, Enterococcus faecium (DC e RCU) e Clostridium butyricum (RCU). No entanto, salientamos a necessidade de estudos mais homogêneos no tratamento da DC com probióticos e prebióticos e o uso de prebióticos na SII.

Combined Chinese and western medicine for endometrial receptivity: A meta analysis of clinical trials

Objective To systemically evaluate the effects of combined Chinese and western medicine in improving endometrial receptivity. Methods A search for relevant articles ran on the CNKI, WanFang, VIP, PubMed, EMBASE and Cochrane library. The randomized controlled trails of combined Chinese and western medicine therapy versus western medicine alone for improving endometrial receptivity were retieved The Revman 5.3 software was used for Meta-analysis according to Cochrane system evaluation method. Results A total of 7 randomized controlled trails involving 499 patients were included. There was statistically significant difference in the growth of clinical pregnancy rate [RR=1.78, 95% CI (1.41, 2.26)], the increase of patients with endometrial thickness [MD=1.42, 95% CI(1.27, 1.58)], the raise of the proportion with type A endometrium [RR=1.25, 95% CI (1.07, 1.45)], the reduction of the patients with endometrial PI [SMD=-1.41, 95% CI (-2.18, -0.64)]. There was no statistically significant difference in the reduction of endometrial RI [SMD=-1.11, 95% CI (-2.52,0.30)]. Conclusions The therapy integrated Chinese and western medicine for endometrial receptivity is better than simple western medicine. But there is less literature on the high quality, suggesting that the methodology of clinical research should be further improved in the future. Key words: Integrated Chinese traditional and western medicine therapy; Endometrial receptivity; Fertilization in vitro; Embryo transfer; Meta-analysis; Systematic review

Triple-negative breast cancer: current state of the art.

Triple-negative breast cancer, defined by a lack of expression of estrogen, progesterone and HER-2 receptors, accounts for 15% of all types of breast cancer. The subtype mainly includes a molecularly distinct subgroup, the basal-like subtype (accounting for 75% of all cases). We attempt to define triple-negative breast cancer and compare it with basal-like disease, review the molecular, pathologic and clinical features of triple-negative disease, provide an overview of a retrospective subset analysis of clinical trials, and outline ongoing therapeutic trials and possible paths for future research. We collected data regarding classification, molecular and clinical features and treatment, drawn from the existing literature, including abstracts and verbal accounts. By the term "basal-like", we defined all cases where gene expression array or more sophisticated immunophenotypes are used for identification. When the analysis is restricted to clinical assay (immunohistochemistry), we refer to "triple-negative". Basal-like breast cancer expresses genes characteristic of basal epithelial cells, which include high-molecular weight basal cytokeratins (CK5/6, CK14, CK17), vimentin, p-cadherin, alpha B crystalline, caveolins 1 and 2 and EGFR. The expression of basal markers (basal cytokeratins and EGFR) is related to a worse prognosis and identifies a clinically distinct subgroup within the triple-negative breast cancer. BRCA1 mutations are present in 11% of triple-negative tumors and even more rare is BRCA2 deficiency. BR-CA1-associated breast cancers types are typically characterized by a high rate of DNA aberrations and defective DNA repair pathways (the so-called "BRCAness"). The use of regimens based on DNA-damaging agents, such as anthracyclines, platinum derivatives and cyclophosphamide seems a sensible option for this breast cancer subtypes. Clinical data support a strong sensitivity to primary chemotherapy with pathologic response rates ranging from 27-45% (with anthracyclines and taxanes) to more than 60% with platinum-based triplets. However, based on retrospective data, major response to chemotherapy does not carry better survival ("triple-negative paradox"). There is no specific targeted therapy in the armamentarium: ongoing trials include anti-angiogenic agents, anti-EGFR and EGFR-TK inhibitors, epothilones and PARP inhibitors. A specific systemic regimen cannot yet be recommended. Moreover, only a few data are available on which treatment selection can be based. Use of the existing cytotoxic agents can be optimized for this patient subgroup by investigating the proliferative signals and the suitability of these signals as therapeutic targets, besides assessing the BRCA1-pathway in this subgroup as regards treatment. A greater understanding of the pathologic and molecular characteristics of this phenotype may lead to customized treatment for these patients.

Coronary artery disease: New Insights into revascularization treatment of diabetic patients.

Diabetes mellitus is an independent cardiovascular risk factor, considered an equivalent of coronary artery disease in terms of prognosis. A history of acute coronary syndrome is a strong predictor of another coronary episode, and cardiovascular complications are the leading cause of mortality in diabetic patients. Many patients with coronary artery disease suffer from concomitant diabetes or pre-diabetes. There are 3 strategies of coronary artery disease treatment: conservative management, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). Since drug-eluting stents (DES) were developed, PCI has become one of the most widespread interventional cardiology procedures performed in Europe and worldwide. Among all coronary risk factors, diabetes mellitus remains the most important predictor of unfavorable outcomes of revascularization therapy. This paper reviews the current evidence regarding revascularization in diabetic patients, with particular emphasis on PCI. A systematic analysis of clinical trials of CABG and PCI, especially with DES, was conducted.

Overview and critical analysis of clinical trials data and epidemiological surveys proving complex mechanism and controversy of anti-tumorigenic activity of metformin

Метформин може да повлияе туморогенезата чрез АМРК по два механизма - индиректно: систематично намаляване на инсулиновите нива и директно: чрез индукция на енергетичен стрес. Индиректно, метформин проявява своя антитуморогенен ефект чрез активиране на LKB1 (тумор супресорен протеин) и последващата таргетна молекула АМРК, която от своя страна потиска активността на таргет на рапамицин при бозайниците (mTOR), сигнален път с централна роля в туморния растеж и патогенеза. Доказано е, че АМРК фосфорилира tuberous sclerosis complex-2 (TSC-2), инхибиращ mTOR. Индукцията на енергетичен стрес, сигнализиращ за намаляване на необходимата за клетката енергия, активира АМРК, което резултира в инхибиция на клетъчния растеж и пролиферация. Активацията на АМРК подпомага адаптацията в условия на енергетичен стрес. Поради засиления интерес към анти-туморогенния ефект на метформин са проведени редица клинични проучвания в последното десетилетие. През 2014 г. е публикувано проучване в бюлетин на Националната академия на науките, САЩ, изказващо предположение, че активацията на АМРК може всъщност да ускорява туморния растеж. Интересен факт е, че мета-анализ на описателни проучвания показва намален риск от злокачествени заболявания сред пациенти, приемащи метформин, докато подобен анализ на данни от рандомизирани контролирани клинични изпитвания не намира връзка между употребата на метформин и редукция на риска от поява на рак. Ретроспективно кохортно проучване, сравняващо връзката между употребата на metformin с други антидиабетни лекарства, доказва че метформин не повлиява риска от злокачествени образувания.

Prediction of Outcome after Traumatic Brain Injury: Comparison of Disease State Index and IMPACT Calculator.

Traumatic brain injury (TBI) is a major cause of death and disability, especially in young adults. A reliable prediction of outcome after TBI is of great importance in clinical practice and research. We aimed to compare performance of the well-established IMPACT calculator and an alternative method, Disease State Index (DSI), in the prediction of six-month outcome after TBI. Performance of the models was evaluated using 2036 patients with moderate or severe TBI from the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) database. Prediction performance of both models was similar. The models with more variables provided better performance than the simpler models. This study showed that the DSI is a valid tool with efficient visualizations that can help clinicians with their decision making process in clinical practice.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study

SummaryThe Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D3 daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.IntroductionThis study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.MethodsWHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).ResultsAmong women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38–1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44–0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.ConclusionThough based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-012-2224-2) contains supplementary material, which is available to authorized users.

Correlated Frailty Model: an Advantageous Approach for Covariate Analysis of Tuberculosis Data

The demonstration of varying treatment effects among different subjects of patients is an important part of the analysis of clinical trials. But issues of censoring, truncation and inclusion criteria complicate the analysis of clinical trial data. Recent advances in proportional hazard methodologies provide regression diagnostics, improved point and interval estimates of the parameters of survival functions, handling of time dependent covariates in the analysis. This paper discusses the interactions between treatment and patient in the presence of censoring and to account heterogeneity using frailty model. The application of the frailty model with respect to pulmonary tuberculosis data are presented and discussed.

Exposure to Antipsychotics and Risk for Stroke

During 2002, analysis of clinical trial data raised concerns that exposure to the atypical antipsychotic drug risperidone led to excess stroke risk in

Analysis of clinical trial articles published in evidence base nursing in the Chinese journal of practical nursing

目的 按Cochrane手册的标准对 1985-2003年共19卷228期的临床护理试验论文进行统计、分析和评价.方法 1985-2003年共19卷228期,对每期杂志进行逐篇查阅,根据Cochrane中心手检指南检索出相关的随机对照试验(RCT)和临床对照试验(CCT)论文.结果 RCT、CCT论文分布情况逐年增加,RCT和CCT占临床试验论文的百分率也逐渐增加. 结论护理学领域的临床护理试验论文研究水平在不断提高.由于RCT 和CCT是论据强度较高的临床试验,在国际上广泛应用,因此,必须规范论文撰写,才能使护理科研成果得到国际认同。

Effects of Hyperglycemia on Ischemic Penumbra, Stroke Outcome

Epidemiologic studies and subgroup analyses of clinical trials have shown that hyperglycemia is a risk factor for poor neurologic outcome following

Evaluating the efficacy of migraine therapy.

In patient surveys and analyses of clinical trial data, patients with migraine cite rapid and complete relief of headache pain as the single most important attribute of a migraine medication. Other desirable attributes cited by patients include lack of migraine recurrence; absence of adverse effects; and relief of associated symptoms, such as nausea, vomiting, and increased sensitivity to light and noise. Data from most clinical trials of migraine drugs use standard endpoints of level of pain relief at 2 hours and percentage of patients who are pain free at 2 hours. Using these endpoints, however, a drug that relieves pain within 30 minutes after administration would be considered equivalent to a drug that does not relieve pain until 1.5 hours after administration. Because patients clearly want relief in less than 2 hours, a time to event analysis, which, in comparison trials, credits a drug for more rapid onset of effect, might be a more useful means of comparing the efficacy of 2 migraine medications. In studies using time to event analyses, the migraine medication rizatriptan has proved superior to sumatriptan in time to pain relief; time to pain-free state; and time to elimination of nausea, photophobia, and phonophobia. Based on these results, rizatriptan may better meet patients' needs than sumatriptan.