Goal-directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A randomised,blinded trial (GODIF trial—First version)

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.     

Prenatal Substance Use and Perceptions of Parent and Partner Use Using the 4P’s Plus Screener

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...     

Phase I study of lapatinib plus trametinib in patients with KRAS -mutant colorectal,non-small cell lung,and pancreatic cancer

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.     

Comparing the efficacy of integrative body-mind-spirit intervention with cognitive behavioral therapy in patient-caregiver parallel groups for lung cancer patients using a randomized controlled trial

Abstract

Purposes/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.     

2014年山西省肿瘤登记地区恶性肿瘤发病与死亡分析

目的探讨2014年山西省肿瘤登记地区恶性肿瘤发病与死亡情况。方法收集2014年全省12个肿瘤登记地区的数据资料,分析不同地区、不同年龄和性别的恶性肿瘤发病率与死亡率特点,同时与全国数据进行比较。结果2014年山西省肿瘤登记地区新发恶性肿瘤11703例(男性6559例,女性5144例),发病率为221.21/10万,中国人口标化发病率为163.91/10万,世界人口标化发病率为163.25/10万;城市地区发病率、中国人口标化发病率分别为247.02/10万、171.35/10万,农村地区分别为205.98/10万、159.03/10万。男性常见恶性肿瘤发病以胃癌、肺癌、食管癌、肝癌、结直肠癌为主,女性以乳腺癌、子宫颈癌、肺癌、食管癌、胃癌为主。恶性肿瘤死亡病例7283例(男性4548例,女性2735例),恶性肿瘤死亡率为137.66/10万,中国人口标化死亡率为99.67/10万,世界人口标化死亡率为100.11/10万;城市地区死亡率、中国人口标化死亡率分别为141.03/10万、92.84/10万,农村地区分别为135.68/10万、103.69/10万。男性常见恶性肿瘤死亡以肺癌、胃癌、肝癌、食管癌、结直肠癌为主,女性以肺癌、胃癌、肝癌、食管癌、子宫颈癌为主。结论山西省肿瘤登记地区恶性肿瘤发病与死亡均以肺癌、上消化道恶性肿瘤和女性子宫颈癌为主,胃癌、子宫颈癌的发病率较高。     

Hypofractionated Concomitant Chemoradiation in Inoperable Locally Advanced Non-small Cell Lung Cancer: A Report on 100 Patients and a Systematic Review

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.

Cost Utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease

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).