Clinical Trial Literature Research Articles

PRO34 Cost-Effectiveness Analysis of Caplacizumab in Combination with Plasmapheresis and Immunosuppression in Patients with Acquired Thrombotic Thrombocytopenia Purpura (ATTP) in Italy

To evaluate the cost-effectiveness of caplacizumab in combination with plasmapheresis (PE) and immunosuppression compared to PE and immunosuppression alone in the treatment of acute episodes of aTTP. A Markov’s model was designed with acute and remission phases, each comprising four mutually exclusive states. The analysis was conducted from the Italian healthcare perspective over a life-time horizon (60 years). Clinical data derived from HERCULES phase 3 clinical trial and systematic literature review. Economic input included direct costs only. Utility and disutility values were obtained from the literature considering analogue clinical conditions validated when aTTP-specific data were not available. Data on healthcare resources were retrieved from HERCULES, literature, aTTP guidelines and published reimbursement tariffs for Italy. Caplacizumab cost was based on the ex-factory price net of temporary discounts by law (base case). Results are presented in terms of incremental cost-effectiveness ratio (ICER) per Quality Adjusted Life Year (QALY) gained, considering an annual discount rate of 3.5% for outcomes and costs. The ICER per QALY was tested for several options of additional discount levels of caplacizumab cost. The use of caplacizumab in combination with PE and immunosuppression is associated with significantly lower intensive care-related costs when compared to PE and immunosuppression alone (€ 14,170.09 vs € 7,032.56) and to a positive difference in survival of 2.99 years (22.47 vs 19.48) and 2.80 QALY (20.20 vs 17.40). The use of caplacizumab leads to an ICER of €45,049 per QALY. The ICER per QALY of caplacizumab is €37,582 with an additional discount of -15%, €35,093 (-20%), €32,603 (-25%) and 30,114 (-30%). Caplacizumab in addition to immunosuppression and PE is considered cost-effective, allowing the healthcare system to achieve greater efficiency in managing the burden of a life-threatening disease such as aTTP.

Efficacy and safety of acupuncture for posterior circulation ischemic vertigo: A protocol for systematic review and meta-analysis.

Background:Posterior circulation ischemic vertigo (PCIV) is one of the most complaint symptoms in clinical, and is associated with high risk of recurrence. Current studies show that acupuncture has therapeutic effect on releasing symptom as well as improving the blood flow of posterior circulation. In this review, we aim to assess the efficacy and safety of acupuncture for PCIV.Methods:Literature of clinical randomized control trials regarding acupuncture for PCIV published before August of 2020 will be searched in databases, including 5 English databases and 4 Chinese databases. For the included studies, methodological quality will be assessed according to Cochrane Risk of Bias Tool, and evidence quality will be evaluated with Grading of Recommendations Assessment, Development and Evaluation guidelines. Data analysis will be performed using Review Manager Software.Results:The primary outcomes involve changes of PCIV symptoms and blood flow velocity of vertebrobasilar. The secondary outcomes include Barthel Index, National Institute of Health Stroke Scale, clinical effectiveness, and adverse reactions.Conclusion:Based on current clinical studies, this systematic review and meta-analysis will provide evidence-based basis for the efficacy and safety of acupuncture in treating PCIV.Trial registration:The protocol for this review has been registered in the INPLASY network (Registration number: INPLASY202070116).

Survey on the Pharmacists Perceptions of Clinical Trial Literature Accessibility

The purpose of this study is to understand the reading habits of Japanese pharmacists regarding clinical trial literature in 2014. Questionnaires were mailed to 1997 pharmacists in Miyagi Prefecture. Six hundreds and five [342 (56.5%) hospital pharmacists and 254 (42.0%) community pharmacists] responded to questionnaires (Response rate: 30.3%). Regarding the question, "Do you habitually read clinical trial literature?", 19.5% of hospital and 8.3% community pharmacists responded "yes", respectively, which showed both pharmacists are not habitual readers of clinical trial literature. That would be because they did not study critical reading of clinical trial literature at pharmacy schools as well as their work environments to access and retrieve clinical trial literature were limited.

Cost-effectiveness of apixaban for prevention of venous thromboembolic events in patients after gynecologic cancer surgery

ObjectiveThe cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data. MethodsMedication costs, adherence rates, event rates, event costs, and utility decrements were estimated using prior clinical trial data and literature review for input into a short-term decision model to simulate outcomes in a hypothetical cohort of 1000 patients. Incremental cost-effectiveness ratios (ICERs) were calculated as net cost difference per quality-adjusted life year (QALY) gained. Input values at which net costs and QALYs were equivalent and ICERs at upper and lower bounds were evaluated. ResultsUsing aggregated costs, apixaban was less expensive and more effective than enoxaparin, and remained so or had high value in all scenarios on sensitivity analysis. Examining disaggregated ICERs, apixaban was cost-effective for deep venous thrombosis (DVT); of high value for clinically-relevant non-major bleeding (CRNMB) ($411); low value for major bleeding ($183,465), VTE-related death ($2,711,229), and all-cause mortality ($297,522); and not cost-effective for pulmonary embolism prevention. ConclusionsApixaban is more cost-effective than enoxaparin for the prevention of postoperative VTE in patients with gynecologic cancer. This appears to be driven largely by DVT and CRNMB prevention.

Abstract 5456: Clinical validation of NAVIFY® Mutation Profiler for solid tumor NGS variant interpretation

Abstract Introduction: Next-Generation Sequencing (NGS) is a standard of care for identifying actionable mutations in solid tumors. Data analysis and adjudication of variants is a significant barrier to NGS adoption in community settings. NAVIFY® Mutation Profiler (NMP) is a cloud-based software that provides curation, annotation, interpretation and reporting of somatic genomic variants identified by NGS. NMP is agnostic to the sample prep, target enrichment, sequencing, and secondary analysis and will accept Variant Call File (VCF) and BAM (Binary Alignment/Map) files. It provides information on genomic variants based on published literature, public annotations, medical guidelines, drug labels and results of clinical trials. The software reports a tiered classification based on modified AMP guidelines, to aid in interpretation of detected variants, inform available therapies, and create a report. To validate accuracy and reproducibility of the NMP software and curation process when used by the intended users, a usability study was performed. Methods: 15 VCF files were prepared, including 12 semi-contrived VCF files across 4 different solid tumor types (3 lung, 3 colon, 3 melanoma and 3 breast). Each file contained on average 8 variants, 4 AMP Tier I variants (strong clinical significance) and 4 non-Tier I variants including SNVs, Indels, Fusions and CNVs. In addition, each case had filtered out variants (based on a variant allele frequency (VAF) <1% or a read depth < 500) with 1 case containing ~9000 and 2 cases containing ~500 filtered out variants. There were 3 VCF files designed to create error messages (1 > 10,000 variants, 1 VAF filter value missing, 1 incorrect reference genome). The study was performed at 3 external sites with 1, 2, and 3 users (total 6 users). Users downloaded the files onto their computers and processed them according to the instructions provided. Results: Correct variant call lists 100% (486/486), variant call list after filter modification 100% (42/42). Most critical was user agreement of Tier classification (Tier I vs. non-Tier I) for a pre-defined filter set: 99.6% (484/486). One user reclassified a MET amplification (lung case) from Tier I to Tier II and one user reclassified a BRAF V600D mutation (colon case) from Tier II to Tier I. In addition, the three cases designed to produce error messages all failed NMP processing: 100% (18/18). Conclusions: NAVIFY® Mutation Profiler is a robust automated solution for variant reporting. The annotation, curation and interpretation provided is highly concordant with molecular genetics experts. With the increasing number of known clinically relevant variants, software capable of automatically identifying and accurately interpreting variants promises to decrease the manual review time necessary to account for and inform on relevant variants. Citation Format: Sidney Alexander Scudder, Anoop Grewal, Lisha Capucion, Guili Zhang, Leonid Formin, Shuba Krishna, Xi Decker, Joanie Chung. Clinical validation of NAVIFY® Mutation Profiler for solid tumor NGS variant interpretation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5456.

Cost-Effectiveness and Net Monetary Benefit of Olaparib Maintenance Therapy Versus No Maintenance Therapy After First-line Platinum-based Chemotherapy in Newly Diagnosed Advanced BRCA1/2-mutated Ovarian Cancer in the Italian National Health Service

PurposeThe aim of this study was to evaluate the cost-effectiveness and net monetary benefit of olaparib maintenance therapy compared with no maintenance therapy after first-line platinum-based chemotherapy in newly diagnosed advanced BRCA1/2-mutated ovarian cancer from the Italian National Health Service (NHS) perspective. MethodsWe developed a lifetime Markov model in which a cohort of patients with newly diagnosed advanced BRCA1/2-mutated ovarian cancer was assigned to receive either olaparib maintenance therapy or active surveillance (Italian standard of care) after first-line platinum-based chemotherapy to compare cost-effectiveness and net monetary benefit of the 2 strategies. Data on clinical outcomes were obtained from related clinical trial literature and extrapolated using parametric survival analyses. Data on costs were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio (ICER), incremental cost-utility ratio (ICUR), and incremental net monetary benefit (INMB) were computed and compared against an incremental cost per quality-adjusted life-year (QALY) gained of €16,372 willingness-to-pay (WTP) threshold. We used deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) to assess how uncertainty affects results; we also performed scenario analyses to compare results under different pricing settings. FindingsIn the base-case scenario, during a 50-year time horizon, the total costs for patients treated with olaparib therapy and active surveillance were €124,359 and €97,043, respectively, and QALYs gained were 7.29 and 4.88, respectively, with an ICER of €9,515 per life-year gained, an ICUR of €11,345 per QALY gained, and an INMB of €12,104. In scenario analyses, considering maximum selling prices for all other drugs, ICUR decreased to €11,311 per QALY and €7,498 per QALY when a 10% and 20% discount, respectively, was applied to the olaparib official price, and the INMB increased to €12,186 and €21,366, respectively. DSA found that the model results were most sensitive to the proportion of patients with relapsing disease in response to platinum-based chemotherapy, time receiving olaparib first-line maintenance treatment, and subsequent treatments price. According to PSAresults, olaparib was associated with a probability of being cost-effective at a €16,372 per QALY WTP threshold ranging from 70% to 100% in the scenarios examined. ImplicationsOur analysis indicates that olaparib maintenance therapy may deliver a significant health benefit with a contained upfront cost during a 50-year time horizon, from the Italian NHS perspective, providing value in a setting with curative intent.

Short-Term Evaluation of the Real-World Efficacy and Safety of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis: A Canadian Multicenter Retrospective Cohort Study [Formula: see text

Systemic therapy for atopic dermatitis (AD) has been challenging with limited safe and efficacious long-term treatment options. In 2017, dupilumab was approved in the United States, Europe, and Canada as the first targeted therapy for patients with moderate-to-severe AD. Despite promising efficacy and safety results in clinical trials, our understanding of dupilumab in clinical practice remains limited with few studies outside clinical trials in literature. The aim of this study is to evaluate the efficacy and safety of dupilumab in clinical practice and discuss any differences in results between clinical trials and real-world results. A retrospective chart review was conducted of consecutive patients receiving dupilumab treatment at two tertiary hospitals in Toronto, Canada, between December 2017 and May 2019. The primary efficacy endpoint was measured by Investigator's Global Assessment (IGA) score of 0/1 at 16 weeks and all adverse events (AEs) experienced by patients were recorded. Of the 93 patients included in the study, 51 (55%) reached IGA 0/1 and 38 (41%) experienced ≥1 AE. There were no severe AEs or discontinuation prior to 16 weeks due to an AE. These findings suggest a higher IGA-based efficacy profile with no newly identified safety concerns in patients treated with dupilumab at two tertiary hospitals in Toronto, Canada, compared to those in randomized controlled trials.

P257 Real-world evidence of TNF inhibition in axial spondyloarthritis: can we generalise the results from clinical trials?

Abstract Background The development and utility of management guidelines assumes that clinical trial findings are generalisable. Seldom is data available to test this. We aimed to determine, in the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS), the proportion of patients commencing TNF inhibition (TNFi) that would/would not have been eligible for clinical trials that led to TNFi treatment guidelines, and whether treatment response differed between the trials and this real-world population. Methods Biologic-naïve spondyloarthritis patients were recruited from across Great Britain. Data was obtained from clinical records, and participants completed postal questionnaires. Participant characteristics were extracted from the placebo-controlled randomised trials in the NICE Health Technology Assessment: TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis (TA383). Descriptive statistics were used to examine differences, including treatment response (ASAS-20), between BSRBR-AS participants who would/would not have been eligible for the clinical trials, and the trial participants. Results 816/2420 (34%) BSRBR-AS participants were commencing TNFi. They were younger (mean age 44 versus 50yrs) with shorter disease duration (15 versus 22yrs), more active disease (BASDAI 6.4 versus 4.0), and poorer function (BASFI 6.2 versus 3.8). Fourteen clinical trials were identified. Compared to trial populations, fewer BSRBR-AS participants were male (67% versus 71%; difference: -4.1% (95%CI: -7.8%, -0.4%)) and fewer were HLA-B27 positive (76% versus 82%; difference: -6.6% (-10.6%, -2.6%)). BSRBR-AS participants were 6yrs older than trial participants, with longer symptom duration. They reported similar disease activity (BASDAI: 6.4 versus 6.2; difference 0.2 (-0.3, 0.7)), although significantly poorer function (BASFI: 6.2 versus 5.1; difference 1.1 (0.5, 1.8)) and spinal mobility (BASMI: 4.2 versus 3.3; difference 1.0 (0.8, 1.1)). Only 333 (41%) of BSRBR-AS participants commencing TNFi would have been eligible for any of the relevant trials. Ten trials reported ASAS20 response criteria, and 864/1401 participants reported a positive treatment response (61.7%). Follow-up data was available for 318 (39%) BSRBR-AS participants, of whom 163 (51.3%) achieved an ASAS20 treatment response (difference: 10.4% (4.4%, 16.5%)). There was no difference in ASAS20 response between those who would/would not have been eligible for clinical trials (50% versus 52%; difference 2.0% (-9.4%, 13.4%)). Conclusion In this real-world population, although the likelihood of meeting response criteria was unrelated to factors determining trial eligibility, the proportion of patients responding to TNFi was lower than in the clinical trial literature. Could this be explained by selection bias? Although fewer BSRBR-AS participants provided follow-up data than in the clinical trials, to account for the observed difference participants lost to follow-up would have to be one-third more likely to achieve ASAS20 response than those who provided follow-up data. We believe this is unlikely. These findings have important implications for the generalisability of trial results, and also for the cost-effectiveness of TNFi agents. Disclosures G.T. Jones: Grants/research support; GTJ is/was a grant holder for research funded by Pfizer, AbbVie, UCB and Celgene., GTJ is/was involved in research that received financial support from Novartis. L.E. Dean: Grants/research support; LED is/was involved in research that received financial support from Pfizer, AbbVie, UCB and Novartis. E. Pathan: None. G.J. Macfarlane: Grants/research support; GJM is/was a grant holder for research funded by Pfizer, AbbVie, UCB and Celgene., GJM is/was involved in research that received financial support from Novartis.

Résistance aux antiplaquettaires : mythe ou réalité ?

The most common anti-platelet therapies use aspirin and/or anti-P2Y12 to contain platelet aggregation during cardiovascular treatments. Aspirin inhibits the protaglandin-thromboxane synthesis pathway, the anti-P2Y12 thienopyridines and pyrimidines block the P2Y12 receptor for ADP which induces stable aggregation of platelets. An abundant literature of clinical trials and comparative reviews of these trials is partially cited in this document. Except in case of suspicion of poor follow-up of the treatments, the search for resistance to these types of treatments is variable, that of aspirin, whose agonist of choice is arachidonate, is considered useless with almost unanimity, for the anti-P2Y12, the positions are not very clear, many conclusions are not to encourage research and monitoring of treatment in the laboratory for non-standardized methods, pre-analytical variability, disparities in the thresholds of the tests used. From the cost of treatments, clopidogrel is still the most used, it is also the product that has been described as having the most cases with resistance. The anti-P2Y12 monitoring methods that appear to be the most relevant use a PGE1 + ADP mixture to assess this resistance, they are yet to be standardized in their methodology, from pre-analytical to postanalytical. However, learned societies mention a reserve for major surgeries and the optimization of their implementation and to verify the observance of the treatments of certain patients. In conclusion, with regard to the methods used, the choice of reference methods remains to be established by learned societies with clear cut-offs. Large randomized clinical trials are to be carried out following the definition of reference methods.

Medicinal Herbs with Potential Anti-Hypertensive Properties: a Systematic Review of Human and Animal Studies

Blood pressure is one of the vital signs, and is the pressure of circulating blood on the walls of blood vessels. When the large arteries lose their natural elasticity and strength, and the smaller ones are narrowed, blood pressure rises and the pressure is exerted by blood on the walls of blood vessels. High blood pressure is dangerous and very harmful for the heart and blood vessels, and is a major cause of mortality in all nations. Many patients tend to use herbal products for controlling their blood pressure, as they are concerned of the side effects of the chemical drugs. There are huge amount of research work exploring the safety and efficacy of a single herb, or combined herbal products on lowering blood pressure, among which some have shown certain effects, and some are negative in results. Grape seed, Garlic, Saffron, Green and White Mulberry, Quince, and some other herbs have more scientific evidence in lowering blood pressure. In this study, we systematically reviewed the scientific literature of clinical trials and animal studies, in which the safety and effectiveness of herbs on lowering blood pressure were evaluated.

Survival Comparison between Melanoma Patients Treated with Patient-Specific Dendritic Cell Vaccines and Other Immunotherapies Based on Extent of Disease at the Time of Treatment.

Encouraging survival was observed in single arm and randomized phase 2 trials of patient-specific dendritic cell vaccines presenting autologous tumor antigens from autologous cancer cells that were derived from surgically resected metastases whose cells were self-renewing in vitro. Based on most advanced clinical stage and extent of tumor at the time of treatment, survival was best in patients classified as recurrent stage 3 without measurable disease. Next best was in stage 4 without measurable disease, and the worst survival was for measurable stage 4 disease. In this study, the survival of these patients was compared to the best contemporary controls that were gleaned from the clinical trial literature. The most comparable controls typically were from clinical trials testing other immunotherapy approaches. Even though contemporary controls typically had better prognostic features, median and/or long-term survival was consistently better in patients treated with this dendritic cell vaccine, except when compared to anti-programmed death molecule 1 (anti-PD-1). The clinical benefit of this patient-specific vaccine appears superior to a number of other immunotherapy approaches, but it is more complex to deliver than anti-PD-1 while equally effective. However, there is a strong rationale for combining such a product with anti-PD-1 in the treatment of patients with metastatic melanoma.

P2.04-08 Preliminary External Validation of the Clinical Definitions of Resistance to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

Immune checkpoint inhibitors (ICIs) have become an important component of treatment for patients with advanced stage non-small cell lung cancer (NSCLC). Unfortunately, the majority of patients on ICIs will eventually progress. Based on the results from a meta-analysis review of the current ICI literature, Gillaspie et al developed a clinical radiographic response criterion to classify patients as having innate, acquired resistance or durable response to ICIs. The objective of this study was to validate this categorization using prospectively collected clinical data. The study population consisted of Stage IIIB and IV, biopsy-proven NSCLC patients from a single institution treated on or off a clinical trial with single agent ICIs in the first, second line or beyond. De-identified tumor data, stage and treatment data long with response to ICIs were collected prospectively into a database. Patients were censored at last date of follow-up if no progression had occurred. Progression-Free survival (PFS) curves and rates were estimated using the Kaplan-Meier method and then compared to the categorization established by the meta-analysis. From April 2012 to January 2018, 231 patients met criteria for inclusion and analysis. Median age was 65 years, 61% were male and 92% white. Forty-three (18.6%) received ICI in the first line, while the remaining 188 were treated in the second line or above. Analogous to the meta-analysis, our single center data demonstrated three distinct sub-populations of response. PFS curve slopes were evaluated and compared between the proposed classification and our single center experience (Table 1). The slopes of the curves are similar for the Innate, Adaptive or Acquired Resistance and Durable Response categories established in the meta-analysis. Our single-center experience resulted in a slightly steeper slope in the innate response category compared to the clinical trial literature. This may be explained by our cohort including patients who are treated in the third line or beyond whereas most of the meta-analysis trials restricted populations to either first or second line only. A steeper PFS curve would be expected in a more heavily treated population.Table 1PFS Slope Meta-AnalysisPFS Slope ValidationInnate Resistance12.914.0Aquired Resistance3.83.4Durable Response1.21.1 Open table in a new tab This single center assessment of the proposed classification for resistance to immune checkpoint inhibitors in non-small cell lung cancer confirms the three distinct subgroups of response based on a comparison of the PFS curves. A formal statistical validation will be performed and presented. Future studies are planned to include prospectively collected data from additional comprehensive cancer centers within the validation cohort.

Serum anti-phospholipase A2 receptor (PLA2R) antibody detected at diagnosis as a predictor for clinical remission in patients with primary membranous nephropathy: a meta-analysis

BackgroundThe diagnostic value of serum M-type phospholipase A2 receptor antibody (sPLA2R-ab) expression in patients with primary membranous nephropathy (PMN) has been established. However, the association between sPLA2R-ab and clinical remission remains uncertain.MethodsWe systematically searched the literature for clinical trials regarding the correlation between sPLA2R-ab expression and clinical remission of PMN patients. Meta-analysis was performed to determine this association. Subgroup analysis, funnel plots, and sensitivity analysis were also performed to investigate heterogeneity or bias.ResultsA total of 11 trials involving 824 patients were included. Patients with positive sPLA2R-ab had a poor clinical remission rate (RR = 0.76, 95%CI 0.68–0.86, P < 0.0001; I2 = 39%), a higher titer of sPLA2R-ab had a lower chance of clinical remission (RR = 0.72, 95%CI 0.59–0.87, P = 0.0006; I2 = 42%),and a higher risk of renal failure (RR = 4.85, 95% CI, 1.83–12.85, P = 0.002; I2 = 0%), without affecting relapse (RR = 0.97, 95% CI, 0.55–1.70; P = 0.92, I2 = 0%). Subgroup analysis by treatment strategies, assay methods, ethnicity, gender, renal function, the approach of ruling out SMN, and the ratio of patients with nephrotic-range proteinuria at baseline showed no significant association between these factors with the prognostic value of sPLA2R-ab for PMN patients. No significant publication bias was found.ConclusionThis meta-analysis adds to the evidence for current guidelines that sPLA2R-ab acts as not only a diagnostic marker but also a pivotal predictor for clinical remission. Therefore, sPLA2R-ab can be considered as a prognostic factor for stratifying PMN patients.

Forecasting the critical role of intermittent therapies for the control of bone resorption

Background:Osteoporosis is a chronic metabolic disease characterized by an imbalance of bone resorption and formation, leading to bone fragility and increased susceptibility to fracture. Parathyroid hormone is approved therapy for the treatment of osteoporosis. Methods:The intermittent therapy of parathyroid hormone requires accurate administration. Meta-analysis is conducted to draw a clear picture of the impact of intermittent therapy and dose rates relative to time, on the osteoporotic patients. A novel mathematical model is presented in this article synchronised with the parametric values, depicted from meta-analysis. Findings:Results obtained from the mathematical model are in close agreement with the results obtained from the clinical trials. The model can be used to forecast the drug potency and dosage rates, to control the vicious cycle of osteoporosis. Interpretations:The intermittent administration of parathyroid hormone, rather than the continuous administration, is more effective, furthermore it is also concluded that a mathematical model, linked with the extensive literature of clinical trials, using meta-analysis can help in drug administration and future clinical studies of drug development.

Clinical benefit, toxicity and cost of metastatic breast cancer therapies: systematic review and meta-analysis.

Oncologists, clinical trialists, and guideline developers need tools that enable them to efficiently review the settings and results of previous studies testing metastatic breast cancer (MBC) drug therapies. We searched the literature to identify clinical trials testing MBC drug therapies. Key eligibility criteria included at least 90% of patients enrolled in thetrial having MBC, therapeutic clinical trials, and Phase II-III studies. Studies were stratified based on patients' tumor receptor statuses and prior exposure to therapy. Survival and toxicity of each drug therapy were estimated from randomized controlled trials using network meta-analysis and from all studies using meta-analysis. These results, along with estimated drug costs, are presented in a web-based visualization tool. We included 1865 studies containing 2676 treatment arms and 184,563 patients in the tool ( http://www.cancertrials.info ). Meta-analysis-based efficacy and toxicity estimates are available for 85 HER-2-directed therapies, 84 hormonal therapies, and 442 undirected therapies. Network meta-analysis-based estimates are available for 16 HER-2-directed therapies, 26 hormonal therapies, and 131 undirected therapies. In this era of increasing choices of MBC therapeutic agents and no superior approach to choosing a treatment regimen, the ability to compare multiple therapies based on survival, toxicity and cost would enable treating physicians to optimize therapeutic choices for patients. For investigators, it can point them in research directions that were previously non-obvious and for guideline designers, enable them to efficiently review the MBC clinical trial literature and visualize how regimens compare in the key dimensions of clinical benefit, toxicity, and cost.

New Anti-Cancer Strategies in Testicular Germ Cell Tumors.

The most common solid malignancy of young men aged 20 to 34 years is testicular germ cell tumor. In addition, the incidence of these tumors has significantly increased throughout the last years. Testicular germ cell tumors are classified into seminoma and nonseminoma germ cell tumors, which take in yolk sac tumor, embryonal cell carcinoma, choriocarcinoma, and teratoma. There are noteworthy differences about therapy and prognosis of seminomas and nonseminoma germ cell tumors, even though both share characteristics of the primordial germ cells. The study is focused on different molecular mechanisms strongly involved in testicular germ cell line tumors underlying new strategies to treat this human neoplasia. Bibliographic data from peer-reviewed research, patent and clinical trial literature, and around eighty papers and patents have been included in this review. Our study reveals that several biomarkers are usefully utilized to discriminate among different histotypes. Moreover, we found new patents regarding testicular germ cell tumor treatments such as the expression of claudin 6, monoclonal antibody (Brentuximab Vedotin), immune checkpoint blockade (ICB) with the FDA-approved drugs pembrolizumab and nivolumab or the oncolytic virus Pelareorep, the combination of selective inhibitors of Aurora kinase. Finally, the pathogenesis of testicular germ cell tumor needs to be deeply understood so that it will improve data on stem cells, tumorigenesis and disease tumor management by more selective treatment.

Acupuncture for dysarthria: systematic review

To systematically evaluate the clinical efficacy of acupuncture for dysarthria, and to explore the rules of acupoints selection for dysarthria. The clinical randomized control trial literature regarding acupuncture for dysarthria published before January of 2018 were searched in databases, including CNKI, Wanfang, VIP, CBM, PubMed, Ebsco, Science Direct and Cochrane Library. The information of included studies was extract and the quality was assessed. The Meta analysis was performed by using RevMan 5.3 software. The frequency of acupoints was calculated by using Excel software to analyzed the rules of acupoints selection. Totally 21 papers were included, involving 1651 patients. The pooled effects of clinical efficacy: heterogeneity test P =0.74, I 2=0%, OR =6.36, 95% CI: 4.55, 8.88, Z =10.84 (P<0.01), indicating the efficacy in the treatment group was significantly higher than that in the control group. The pooled effects of the symptom score in Frenchay scale: heterogeneity test P =0.56, I 2=0%, WMD =3.20, 95% CI: 1.38, 5.02, Z =3.45 (P<0.01), indicating the efficacy in the treatment group was significantly higher than that in the control group. The acupoints with frequency of more than 5 times were Fengchi (GB 20), Yuye (EX-HN 13), Jinjin (EX-HN 12), Lianquan (CV 23), Baihui (GV 20), tongue-three needles and Yamen (GV15). The meridians with frequency of more than 5 times were the extra channels, governor vessel, gallbladder channel, conception vessel and stomach channel. The clinical efficacy of acupuncture combined with speech training/regular treatment is significantly superior to that of control group (speech training, medication, regular treatment); acupuncture is safe and effective for dysarthria; the majority of selected acupoint is local acupoints around tongue, throat and neck, as well as extra points and empirical points. However, high-quality randomized controlled trials with large sample sizes are still needed to provide further evidence.

A Systematic Review of Breast Care for Postpartum Mothers.

The purpose of this study was to identify nursing interventions for the postpartum breast care of mothers and determine the effectiveness of interventions for breast pain and engorgement by systematic review. Eight national and international databases were reviewed to retrieve and collect randomized controlled trial and controlled clinical trial literature published up to March 2015. Two reviewers independently selected the studies and performed data abstraction and validation. The risk of bias was assessed using Cochrane criteria. A meta-analysis of the studies was performed to analyze the data. The meta-analysis showed that breast massage, along with routine breast care, resulted in a 3.52-point reduction in pain on a 10-point visual analogue scale. Meta-analysis of therapy with cold cabbage leaves and routine breast care showed a pain reduction of 0.54 points. Meta-analysis of cold cabbage leaf application in the experimental group versus cold compress therapy in the comparison group showed a pain reduction of 0.44 points. Meta-analysis of cold cabbage leaf application and routine breast care showed an engorgement reduction of 0.67 points. The results of the analysis of 12 articles showed that hot and cold compresses, breast massage, and cabbage application were effective for postpartum breast pain and engorgement.

Intraoperative Vaginal Perforation During Various Mid-Urethral Sling Procedures Treating Female Stress Urinary Incontinence

Background: Incidence of intraoperative vaginal perforation is generally considered to be low but varies among different procedures. Vaginal perforation could not only prolong the surgeries and aggravate surgical trauma but also result in postoperative discomfort or even a second surgery.Method: Vaginal perforation, vaginal epithelial perforation, vaginal wall perforation, vaginal penetration, urinary incontinence were searched in PubMed, Cochrane, Embase database to identify the qualified clinical trial and relevant literature sources were also searched.Results: A total of 9223 cases of from 33 trials from literatures and 387 cases from our own trail were analyzed, which provided detailed data on intraoperative vaginal perforation. Incidence of intraoperative vaginal perforation during mid-urethral sling surgery treating stress urinary incontinence was generally low, which was 1.56%. Incidence of intraoperative vaginal perforation during transobturator (TOR) procedure was higher than that during retropubic (RPR) procedure, which were 2.11% and 0.89% respectively. Incidence of intraoperative vaginal perforation during outside-to-inside TOR procedure like TOT and MONARC was higher than that during inside-to-outside TOR procedure like TVT-O, which were 2.74% and 1.52%, respectively. Incidence of intraoperative vaginal perforation during single-incision surgery like H-type TVT-SECUR reached 1.97%, while no report on U-type TVT-SECUR surgeries.Conclusion: The incidence of intraoperative vaginal during mid-urethral sling procedures for female stress urinary incontinence is fairly high. Vaginal perforation was more common in trans-obturator route (TOR) than retropubic route (RPR). In TOR route, it was less frequent in inside-to-outside procedure than outside-to-inside procedure. Surgery proficiency could also have an impact on this complication.

A review of oncologic therapeutic phase III clinical trial literature: Exploring the reporting of clinical trial data of older patients with cancer.

70 Background: With demographic shifts leading to an aging cancer population, the American Society of Clinical Oncology (ASCO) has recommended that journal editors improve the reporting of clinical trial data specific to older adults. This study aimed to assess the current reporting status of clinical trial data regarding older adults with cancer. Methods: This was a review of oncologic therapeutic phase-3 clinical trial data published from 07/01/2016-06/30/2017. Based on a keyword search of EMBASE and PubMed, 929 manuscripts were identified. Removing duplicates (n = 116) and articles that did not meet this study’s cancer inclusion criteria (n = 589), a total of 224 were identified. In the pilot phase there was 85% agreement among the reviewers. Results: Thus far, 197 papers (88%), have been independently reviewed with 118 evaluated by more than one reviewer. Reviewed papers were published in 57 journals including Journal of Clinical Oncology (28, 14.2%), Lancet Oncology (25, 12.7%), and NEJM (20, 10.2%). Much of the literature focused upon the following cancer sites: Breast (33, 16.7%), Lung (27, 13.7%), Colorectal (18, 9.1%), and Prostate (12, 6.1%). 175 articles included inclusion/exclusion criteria, 32 (16.2%) had upper age exclusion criteria. Age was presented in 184 articles and data was stratified by age in 84 (42.6%). Age stratification of effectiveness and toxicity were presented in the results section in 65 (38.2%) and 21 (14.4%). Effectiveness by age was in the discussion section in 37 (18.8%) and toxicity by age in 16 (8.1%). Reviewers could not determine the proportion of study participants who were older adults in 111 articles (56.2%). In the remainder of the articles, the proportion ranged from 0% to 81%, except one in which all participants were older adults. Conclusions: A slim minority of phase-3 oncologic clinical trials included and discussed age-referenced results regarding the effectiveness and toxicity of treatments in older adults. Clinical investigators and journal editors should consider the ASCO recommendation and increase the reporting of oncologic clinical trial data specific to older adults.