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Sine Wichmann Martin Schønemann-Lund Anders Perner Theis S. Itenov Theis Lange Christian Gluud Rasmus E. Berthelsen Anne C. Brøchner Jørgen Wiis Morten H. Bestle 《Acta anaesthesiologica Scandinavica》2023,67(4):470-478
Background
Salt and water accumulation leading to fluid overload is associated with increased mortality in intensive care unit (ICU) patients, but diuretics' effects on patient outcomes are uncertain. In this first version of the GODIF trial, we aimed to assess the effects of goal-directed fluid removal with furosemide versus placebo in adult ICU patients with fluid overload.Methods
We conducted a multicentre, randomised, stratified, parallel-group, blinded, placebo-controlled trial in clinically stable, adult ICU patients with at least 5% fluid overload. Participants were randomised to furosemide versus placebo infusion aiming at achieving neutral cumulative fluid balance as soon as possible. The primary outcome was the number of days alive and out of the hospital at 90 days.Results
The trial was terminated after the enrolment of 41 of 1000 participants because clinicians had difficulties using cumulative fluid balance as the only estimate of fluid status (32% of participants had their initially registered cumulative fluid balance adjusted and 29% experienced one or more protocol violations). The baseline cumulative fluid balance was 6956 ml in the furosemide group and 6036 ml in the placebo group; on day three, the cumulative fluid balances were 1927 ml and 5139 ml. The median number of days alive and out of hospital at day 90 was 50 days in the furosemide group versus 45 days in the placebo group (mean difference 1 day, 95% CI -19 to 21, p-value .94).Conclusions
The use of cumulative fluid balance as the only estimate of fluid status appeared too difficult to use in clinical practice. We were unable to provide precise estimates for any outcomes as only 4.1% of the planned sample size was randomised. 相似文献94.
95.
Janitz Amanda E. Schraw Jeremy M. Xu Chao Lupo Philip J. 《Cancer causes & control : CCC》2022,33(3):483-488
Cancer Causes & Control - Congenital malformations are strong risk factors for childhood cancer. Our objective was to determine whether cancer survival differs by birth defect status among... 相似文献
96.
Aleksandra Polkowska Anna Skoczyńska Iwona Paradowska-Stankiewicz Paweł Stefanoff Waleria Hryniewicz Alicja Kuch Outi Lyytikäinen J. Pekka Nuorti 《Vaccine》2019,37(10):1365-1373
Background
Poland introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into the childhood immunization program in January 2017. During previous decades, considerable changes had occurred in the surveillance system for invasive pneumococcal disease. Therefore, to provide baseline data on pneumococcal diseases before PCV10 introduction, we evaluated the epidemiology of pneumococcal meningitis (PM), the only syndrome monitored consistently since 1970.Methods
Based on laboratory-confirmed cases reported during 2005-2015, we calculated the reported rates, serotypes distribution and antimicrobial resistance of pneumococcal meningitis isolates. Data from the mandatory national surveillance system was linked with data on cerebrospinal fluid isolates submitted to the National Reference Centre for Bacterial Meningitis. We used negative binomial regression with Newey West method to test for trend in rates of pneumococcal meningitis notified during 2005-2015 and Chi-squared test to assess changes in the serotype distribution from 2008-2011 to 2012-2015.Results
From 2005 to 2015, the overall reported incidence of PM increased from 0.21 to 0.47 cases per 100,000 population, average yearly increase of 7% (rate ratio 1.07; 95% CI 1.06–1.08). The increase was primarily due to annual increase of 3% (1.02–1.05) among 15–49?years of age, 12% (95% CI: 1.10–1.13) among 50–64?years of age, 18% (95% CI: 1.16–1.19) among persons 65–74?years of age and 9% (95% CI 1.07–1.10) among persons ≥75?years of age. In children <5?years of age, serotypes included in PCV10 and PCV13 accounted for 75% and 80% of reported isolates, respectively. From 2008-2011 to 2012-2015, the proportion of PM cases caused by PCV10 serotypes decreased from 52% to 41% (p?<?0.01). Overall, 28% of isolates were resistant to penicillin and 13% were non-susceptible to cefotaxime.Conclusions
The introduction of PCV10 into national immunization program may have considerable impact on disease burden, especially on number of cases caused by isolates non-susceptible to antimicrobials. 相似文献97.
Philip J. Lupo Ruth E. Luna-Gierke Tiffany M. Chambers Björn Tavelin Michael E. Scheurer Beatrice Melin Karin Papworth 《International journal of cancer. Journal international du cancer》2020,146(3):791-802
Perinatal factors have been associated with soft tissue sarcomas (STS) in case-control studies. However, (i) the contributions of factors including fetal growth remain unknown, ( ii ) these factors have not been examined in cohort studies and (iii) few assessments have evaluated risk in specific STS subtypes. We sought to identify the role of perinatal and familial factors on the risk of STS in a large population-based birth cohort. We identified 4,023,436 individuals in the Swedish Birth Registry born during 1973–2012. Subjects were linked to the Swedish Cancer Registry, where incident STS cases were identified. We evaluated perinatal and familial factors obtained from Statistics Sweden, including fetal growth, gestational age, and presence of a congenital malformation. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for associations between perinatal factors and STS overall, as well as by common subtypes. There were 673 individuals diagnosed with STS in 77.5 million person-years of follow-up. Having a congenital malformation was associated with STS (IRR = 1.70, 95% CI: 1.23–2.35). This association was stronger (IRR = 2.90, 95% CI: 1.25–6.71) in recent years (2000–2012). Low fetal growth was also associated with STS during the same time period (IRR = 1.86, 95% CI: 1.05–3.29). Being born preterm was associated with rhabdomyosarcoma (IRR = 1.74, 95% CI: 1.08–2.79). In our cohort study, those with congenital malformations and other adverse birth outcomes were more likely to develop a STS compared to their unaffected contemporaries. These associations may point to disrupted developmental pathways and genetic factors influencing the risk of STS. 相似文献
98.
Sanne C. F. A. Huijberts Robin M. J. M. van Geel Emilie M. J. van Brummelen Frans L. Opdam Serena Marchetti Neeltje Steeghs Saskia Pulleman Bas Thijssen Hilde Rosing Kim Monkhorst Alwin D. R. Huitema Jos H. Beijnen Ren Bernards Jan H. M. Schellens 《Cancer chemotherapy and pharmacology》2020,85(5):917-930
KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated. 相似文献
99.
Michael T Milano Veronica L S Chiang Scott G Soltys Tony J C Wang Simon S Lo Alexandria Brackett Seema Nagpal Samuel Chao Amit K Garg Siavash Jabbari Lia M Halasz Melanie Hayden Gephart Jonathan P S Knisely Arjun Sahgal Eric L Chang 《Neuro-oncology》2020,22(12):1728
BackgroundThe American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines.MethodsThe panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness.ResultsThe panel agreed that SRS alone is usually appropriate for those with good performance status and 2–10 asymptomatic BM, and usually not appropriate for >20 BM. For 11–15 and 16–20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2–4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options.ConclusionsFor patients with 2–10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists. 相似文献
100.
Hallet Julie Look Hong Nicole J. Zuk Victoria Davis Laura E. Gupta Vaibhav Earle Craig C. Mittmann Nicole Coburn Natalie G. 《Gastric cancer》2020,23(3):373-381
Gastric Cancer - Esophagogastric cancer (EGC) is one of the deadliest and costliest malignancies to treat. Care by high-volume providers can provide better outcomes for patients with EGC. Cost... 相似文献