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      Renal Morbidity of 6% Hydroxyethyl Starch 130/0.4 in 9000 Propensity Score Matched Pairs of Surgical Patients

      research-article
      , MD, PhD * , , , MD, PhD
      Anesthesia and Analgesia
      Lippincott Williams & Wilkins

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          BACKGROUND:

          Several studies of critically ill patients reported that fluid resuscitation with hydroxyethyl starch (HES) solutions damages the kidneys, but their use for surgical patients is debated. Because different HES preparations have different safety profiles, we sought to determine whether 6% third-generation HES 130/0.4 was associated with renal morbidity when used for surgical patients.

          METHODS:

          We identified adults enrolled in a Japanese nationwide medical database who underwent surgery between 2014 and 2016, with HES 130/0.4 or without it (controls). These groups were balanced with propensity score matching in a 1:1 ratio without replacement by multivariable logistic regression with 36 covariates, including demographic characteristics, preoperative comorbidities, and anesthetic/surgical procedures. The primary outcome was the incidence of acute kidney injury (AKI) in patients receiving intraoperative HES and controls. Secondary outcomes were assessing whether HES was associated with worsening AKI stage, the incidence of renal-replacement therapy (RRT), hospital length-of-stay, and in-hospital 30-day mortality. Tertiary outcomes include the use of vasoactive agents and the fluid requirement on the day of surgery. Comparative analysis was made with χ 2, Mann-Whitney U test, or the ordinal logistic regression analysis.

          RESULTS:

          Of 76,048 patients in the database, 58,425 were eligible: 9542 received HES and 48,883 controls. Propensity score matching identified 8823 matched pairs. The incidence of AKI was 6.2% (548/8823) in the HES group and 5.6% (492/8823) in controls (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.99–1.27; P = .07). Compared to controls, HES was not associated with worsening AKI stage (OR, 0.89; 95% CI, 0.79–1.01; P = .08). The incidence of RRT was lower in the HES group than that in controls (0.2% vs 0.4%, respectively; OR, 0.51; 95% CI, 0.29–0.91; P = .02). Median [interquartile range] hospital stay was 1 day longer in the HES group (12 [8–21] vs 11 [7–20] days; P < .001), but in-hospital 30-day mortality did not differ between groups (0.5% vs 0.6%, respectively: OR, 0.83; 95% CI, 0.56–1.24; P = .36). The use rate of vasoactive agents and the median net fluid requirement on the day of surgery were higher in the HES group (80.5% vs 70.0%: P < .001, 88.1 vs 73.6 mL/kg; P < .001, respectively) compared to controls.

          CONCLUSIONS:

          The present study did not demonstrate that 6% HES 130/0.4 increased the incidence and the severity of postoperative AKI. It was associated with a lower incidence of RRT when used for surgical patients.

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          Most cited references20

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          Pharmaceutical industry sponsorship and research outcome and quality: systematic review.

          To investigate whether funding of drug studies by the pharmaceutical industry is associated with outcomes that are favourable to the funder and whether the methods of trials funded by pharmaceutical companies differ from the methods in trials with other sources of support. Medline (January 1966 to December 2002) and Embase (January 1980 to December 2002) searches were supplemented with material identified in the references and in the authors' personal files. Data were independently abstracted by three of the authors and disagreements were resolved by consensus. 30 studies were included. Research funded by drug companies was less likely to be published than research funded by other sources. Studies sponsored by pharmaceutical companies were more likely to have outcomes favouring the sponsor than were studies with other sponsors (odds ratio 4.05; 95% confidence interval 2.98 to 5.51; 18 comparisons). None of the 13 studies that analysed methods reported that studies funded by industry was of poorer quality. Systematic bias favours products which are made by the company funding the research. Explanations include the selection of an inappropriate comparator to the product being investigated and publication bias.
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            Acute kidney injury-epidemiology, outcomes and economics.

            Acute kidney injury (AKI) is a widespread problem of epidemic status. Compelling evidence indicates that the incidence of AKI is rapidly increasing, particularly among hospitalized patients with acute illness and those undergoing major surgery. This increase might be partially attributable to greater recognition of AKI, improved ascertainment in administrative data and greater sensitivity of consensus diagnostic and classification schemes. Other causes could be an ageing population, increasing incidences of cardiovascular disease, diabetes mellitus and chronic kidney disease (CKD), and an expanding characterization of modifiable risk factors, such as sepsis, administration of contrast media and exposure to nephrotoxins. The sequelae of AKI are severe and characterized by increased risk of short-term and long-term mortality, incident CKD and accelerated progression to end-stage renal disease. AKI-associated mortality is decreasing, but remains unacceptably high. Moreover, the absolute number of patients dying as a result of AKI is increasing as the incidence of the disorder increases, and few proven effective preventative or therapeutic interventions exist. Survivors of AKI, particularly those who remain on renal replacement therapy, often have reduced quality of life and consume substantially greater health-care resources than the general population as a result of longer hospitalizations, unplanned intensive care unit admissions and rehospitalizations.
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              Scope and impact of financial conflicts of interest in biomedical research: a systematic review.

              Despite increasing awareness about the potential impact of financial conflicts of interest on biomedical research, no comprehensive synthesis of the body of evidence relating to financial conflicts of interest has been performed. To review original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research. Studies were identified by searching MEDLINE (January 1980-October 2002), the Web of Science citation database, references of articles, letters, commentaries, editorials, and books and by contacting experts. All English-language studies containing original, quantitative data on financial relationships among industry, scientific investigators, and academic institutions were included. A total of 1664 citations were screened, 144 potentially eligible full articles were retrieved, and 37 studies met our inclusion criteria. One investigator (J.E.B.) extracted data from each of the 37 studies. The main outcomes were the prevalence of specific types of industry relationships, the relation between industry sponsorship and study outcome or investigator behavior, and the process for disclosure, review, and management of financial conflicts of interest. Approximately one fourth of investigators have industry affiliations, and roughly two thirds of academic institutions hold equity in start-ups that sponsor research performed at the same institutions. Eight articles, which together evaluated 1140 original studies, assessed the relation between industry sponsorship and outcome in original research. Aggregating the results of these articles showed a statistically significant association between industry sponsorship and pro-industry conclusions (pooled Mantel-Haenszel odds ratio, 3.60; 95% confidence interval, 2.63-4.91). Industry sponsorship was also associated with restrictions on publication and data sharing. The approach to managing financial conflicts varied substantially across academic institutions and peer-reviewed journals. Financial relationships among industry, scientific investigators, and academic institutions are widespread. Conflicts of interest arising from these ties can influence biomedical research in important ways.
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                Author and article information

                Journal
                Anesth Analg
                Anesth. Analg
                ANE
                Anesthesia and Analgesia
                Lippincott Williams & Wilkins
                0003-2999
                1526-7598
                16 December 2019
                June 2020
                : 130
                : 6
                : 1618-1627
                Affiliations
                From the [* ]Department of Anesthesiology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
                []Department of Anesthesiology, Toho University Ohashi Medical Center, Tokyo, Japan.
                Author notes
                Address correspondence to Hideki Miyao, MD, PhD, Department of Anesthesiology, Saitama Medical Center, Saitama Medical University, 1981, Kamoda, Kawagoe, Saitama 350-8550, Japan. Address e-mail to miyaoh@ 123456saitama-med.ac.jp .
                Article
                00023
                10.1213/ANE.0000000000004592
                7249485
                31856004
                80960032-4d2c-456f-b41d-7eae04043c85
                Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 14 November 2019
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