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41.
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42.
43.
Oga Emmanuel. A. Peters Erica. N. Mark Katrina Trocin Kathleen Coleman-Cowger Victoria. H. 《Maternal and child health journal》2019,23(2):250-257
Maternal and Child Health Journal - Background Prenatal substance use screening is recommended. The 4 P’s Plus screener includes questions on perceived problematic substance use in parents... 相似文献
44.
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
45.
Bobo H. P. Lau Ting-Kin Ng Yat-Lui Fung Tai-Chung Lam Tsz-Him So 《Journal of psychosocial oncology》2020,38(4):389-405
AbstractPurposes/objectives: This paper reports the comparative efficacies of integrative body-mind-spirit intervention (I-BMS) and cognitive behavioral therapy (CBT) in patient-caregiver parallel groups for Chinese patients with lung cancer.Design: Randomized controlled trial (RCT).Methods: One hundred and fifty-seven patient-caregiver dyads with no marked functional impairment were randomized into one of the two interventions with eight weekly patient-caregiver parallel groups. Assessments were conducted at baseline, within one, eight- and sixteen-weeks post-intervention. Effects of treatment group across time were analyzed by multilevel modeling.Findings: CBT led to greater reduction in emotional vulnerability than I-BMS. I-BMS resulted in greater increase in overall QoL and spiritual self-care, and more reduction in depression than CBT. Patients in both interventions experienced improvement in physical, emotional and spiritual, except social, domains of QoL.Conclusion: I-BMS was more efficacious for diverse domains of QoL, and CBT was more effective for emotional well-being, despite the relatively small between-group effect sizes.Implications for psychosocial providers/policy: (1) With the expanding repertoire of psychosocial interventions for families facing lung cancer, it has become imperative to investigate the comparative efficacies of empirically supported and culturally adapted interventions. (2) Our findings show that I-BMS was more effective for diverse domains of QoL, while CBT was more efficacious with emotional well-being, although both interventions led to significant improvements in physical, emotional and spiritual domains of patient QoL. (3) Patient-caregiver parallel groups have been shown to be effective for enhancing QoL of Chinese lung cancer patients. (4) Care professionals are encouraged to dispense interventions based on the idiosyncratic needs and preferences of the patients to maximize the treatment effects. 相似文献
46.
47.
M.S. Iqbal G. Vashisht R. McMenemin P. Atherton F. McDonald T. Simmons A. Bradshaw J. Kovarik H. Turnbull L. Dodd P. Mulvenna A. Greystoke 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):e1-e10
Aims
Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.Materials and methods
One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan–Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.Results
In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.Conclusion
Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial. 相似文献48.
Marita Zimmermann Solomon J. Lubinga Reiner Banken David Rind Geri Cramer Patricia G. Synnott Richard H. Chapman Sonya Khan Josh Carlson 《Value in health》2019,22(2):161-167
Objective
The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration–approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC).Study Design
A 2-state Markov model, alive and dead, with a lifetime horizon.Methods
Visual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs.Results
VN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective.Conclusions
At the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered. 相似文献49.
Theresa M. Thole Joern Toedling Annika Sprüssel Sebastian Pfeil Larissa Savelyeva David Capper Clemens Messerschmidt Dieter Beule Stefanie Groeneveld-Krentz Cornelia Eckert Guido Gambara Anton G. Henssen Sabine Finkler Johannes H. Schulte Anja Sieber Nils Bluethgen Christian R. A. Regenbrecht Annette Künkele Marco Lodrini Angelika Eggert Hedwig E. Deubzer 《International journal of cancer. Journal international du cancer》2020,146(4):1031-1041
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
50.
Bhavana Pothuri Allison L. Brodsky Joseph A. Sparano Stephanie V. Blank Mimi Kim Dawn L. Hershman Amy Tiersten Brian F. Kiesel Jan H. Beumer Leonard Liebes Franco Muggia 《Cancer chemotherapy and pharmacology》2020,85(4):741-751
Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy. 相似文献