Minimally Invasive Technique Leads to Decreased Morbidity and Mortality in Small Bowel Resections Compared to an Open Technique: An ACS-NSQIP Identified Target for Improvement
Shaun DalyAndrew M. PopoffLouis FoggAmanda B. FrancescattiJonathan A. MyersKeith W. MillikanDaniel J. DezielMinh B. Luu
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Bowel resection
Invasive surgery
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Abstract Introduction Mavacamten, a first-in-class selective inhibitor of cardiac myosin, was demonstrated in EXPLORER-HCM (NCT03470545) to be superior to placebo in achieving a primary endpoint of either (1) a ≥1.5 mL/kg/min increase in peak oxygen consumption (pVO2) and at least one New York Heart Association (NYHA) class reduction, or (2) a ≥3.0 mL/kg/min pVO2 increase without NYHA class worsening, in adults with obstructive hypertrophic cardiomyopathy (oHCM). However, the observed benefits of mavacamten were broader than the primary endpoint, suggesting a complex effect of the drug beyond improvements in these two parameters. Purpose A post hoc investigation of mavacamten clinical effects beyond the primary endpoint of EXPLORER-HCM. Methods EXPLORER data at week 30 were analyzed to evaluate improvements from baseline in primary (specified above), secondary (e.g. postexercise left ventricular outflow tract gradient and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score) and exploratory endpoints (e.g. circulating NT-ProBNP and cardiac Troponin I). Responses were classified as improved or not improved based on published thresholds, clinical standards and analyses of the EXPLORER data. Patients were grouped according to their improvement status using unsupervised hierarchical clustering. Results The cluster analysis resulted in four main groups with the following trends (Table); Group 1 = patients who met the primary endpoint and showed improvement in secondary/exploratory endpoints; Group 2 = patients with improvement in secondary/exploratory endpoints who did not meet the primary endpoint; Group 3 = patients who met the primary endpoint without substantial secondary/exploratory endpoint responses; Group 4 = patients without appreciable improvement in any endpoint. A substantially larger proportion of patients in Group 1 received mavacamten compared with placebo (88% vs. 12%, respectively). A similar trend was observed in Group 2 patients who exhibited improvements in secondary/exploratory endpoints (85% mavacamten vs. 15% placebo). Group 3 consisted predominantly of placebo-treated patients who met the primary endpoint but had negligible responses to secondary/exploratory endpoints (5% mavacamten vs. 95% placebo). Group 4 consisted predominantly of placebo-treated patients without appreciable clinically relevant responses from this analysis (10% mavacamten vs. 90% placebo). Conclusions Mavacamten was associated with clinical improvements beyond the primary endpoint of EXPLORER-HCM and was predominantly accompanied by amelioration of other measures associated with oHCM pathophysiology. In contrast, most placebo-treated patients who met the primary endpoint did not exhibit improvement in the underlying pathophysiology. These findings suggest a potential underestimation of mavacamten clinical impact based on the primary endpoint and prompt a deeper examination of mavacamten efficacy in patients with oHCM based on other clinically relevant endpoints. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb
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With the developing of medical technology,more and more minimally invasive surgeries are born,and patients have benefited from them.Widely performed minimally invasive surgeries including:intervention treatment,transvaginal surgery,laparoscopic surgery,minimally access surgery and etc.The minimally invasive idea is established because of the improvement of entire medical model based on minimally invasive techniques.With the minimally invasive idea,different but best minimally invasive surgeries are scientifically chosen to different diseases and disease-centered substitutes for technique-centered,enable patients to get the perfect therapeutic effect.
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Vitreoretinal surgery has entered the era of minimally invasive surgery after decades of development. The development of equipment and technology, represented by 25G and 23G vitrectomy, makes the incision smaller and sutureless. However, the "micro-incision" surgery is not the same as "minimally invasive surgery". The key of "minimally invasive surgery" is that the surgeons should have a strong "minimally invasive" consciousness, always follow the "minimally invasive principle", produces minimal trauma to obtain the best outcome. The ideal minimally invasive vitrectomy should be the perfect combination of "minimally invasive technique" and "minimally invasive devices and equipment" under the guidance of "minimally invasive consciousness".
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Little data exists on the prognostic role of inspiratory muscle strength (PImax) in chronic heart failure (CHF). Training studies, however, frequently use it as a therapeutic target and surrogate marker for prognosis. The prognostic value of changes of PImax that allow this extrapolation is unknown.Patients with stable CHF were prospectively included and 1-year and all-time event rates recorded for endpoint analysis.In 158 patients (85% men; New York Heart Association functional class: 2.4+/-0.6), PImax was measured along with clinical evaluations at two visits, the initial visit and the second visit, 6.4+/-1.4 months apart. The mean follow-up was 59+/-34 months.Overall, 59 patients (37%) reached the primary endpoint of death or hospitalization (endpoint positive), and overall mortality rate (secondary endpoint) was 26% (42 patients). PImax did not differ between endpoint-negative and endpoint-positive patients, both at the initial and at the second visit (8.3+/-5.6 vs. 7.3+/-3.4 kPa and 8.8+/-6.0 vs. 7.9+/-3.6 kPa, respectively; P=NS), and both groups showed increased PImax (0.6+/-2.6 vs. 0.6+/-2.8 kPa; P=NS). Cox analyses found neither the absolute nor the relative change of PImax to be significant predictors for the primary and secondary endpoints (P=NS for both), both for the 1-year and for the all-time event rates. Endpoint rates did not differ between patients showing increasing or decreasing PImax (P=NS; relative risk (RR): 0.77; 95% confidence interval: 0.47-1.27).Trials focusing on inspiratory muscle function should use the actual levels of PImax as a surrogate marker to represent prognostic information, rather than relative or absolute changes. This is the first study to investigate the prognostic information of the changes of PImax over time, regarding both short-term and long-term morbidity and mortality in patients with stable CHF.
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The aim of this study was to analyse trial variables affecting drug approval in metastatic breast cancer (MBC). A literature search from 2000 to 2012 retrieved 66 phase III randomized controlled trials with reported primary endpoints in MBC and known outcomes in terms of approval. The influence of the primary endpoint, the line of therapy, crossover and the sample size was analysed. The primary endpoints used most frequently were progression-free survival (PFS) and time to progression or time to treatment failure (N=47; 71%). Overall survival (OS) was a primary endpoint in nine trials (14%). In 26 trials (39%), statistically significant results were found with respect to the primary endpoint, and in 13 trials (20%), this was found with respect to the secondary endpoint. Gains in OS were found in 12 trials (18%), whereas a benefit to PFS was found in 30 trials (46%). The average median OS was 23.1 months. Postprogression survival accounted for 64% of OS. Trials with crossover did not have OS as the primary endpoint. Trials that resulted in drug approval had a more pronounced gain in OS or PFS and had more patients than those without regulatory consequences. PFS was the main primary endpoint in randomized clinical trials in MBC and was significantly associated with drug approval. OS benefit was rarely achieved in trials where this was not the primary endpoint. The number of randomized patients, the primary endpoint and crossover are factors linked to regulatory requirements for approval, which should be considered in future trial designs.
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Summary The success of a clinical trial is judged by achieving statistical and clinical significance on the primary endpoint. This is particularly relevant in those trials that are initiated to achieve regulatory approval of a new therapeutic agent. Selection of an endpoint for which statistical significance will be too difficult to achieve can result in clinical trial data that fails to meet regulatory requirements for product approval. Over the past decade, significant progress has been made in development and refinement of the study design for evaluating new therapeutic agents targeted for the treatment of irritable bowel syndrome. One aspect of trial design that has been advanced is recognition of the endpoint of ‘Adequate Relief.’ Adequate relief has been used as a primary endpoint in treatment trials with alosetron, cilansetron and dextofisopam. With each of these agents, statistically significant benefit was seen when compared to placebo. As an endpoint, adequate relief is responsive, reproducible and moves in the same direction as other meaningful measures, and, therefore, displays properties of a validated endpoint. Adequate relief should be considered an acceptable primary endpoint by regulatory agencies for use in clinical trials of novel therapeutic agents for irritable bowel syndrome.
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The advantage of the minimally invasive surgery is minimally invasive, few impacts on the body, less pain and rapid recovery. In recent years, laparoscopic surgery and arthroscopic surgery as the representative of the minimally invasive surgery have been developed rapidly in the veterinary medicine. Minimally invasive surgery is not only used for animal reproduction and diagnosis of disease, but also for treatments of the disease. Minimally invasive techniques and their applications were briefly described in veterinary medicine in this paper.
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With the development of Micro Electro Mechanical System(MEMS), it's application in the fields of biomedical engineering becomes a vital consideration. This paper describes the advantages of Minimally invasive Surgery (MIS) and its applications. A novel medical endoscope driven by micro robot is also introduced.
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