Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit - a before and after analysis

<p>Abstract</p> <p>Background</p> <p>Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation.</p> <p>Methods</p> <p>In our surgical ICU (12 beds) and cardiothoracic ICU (14 beds) at a tertiary academic center, we implemented a nurse-centered computerized potassium protocol integrated with the pre-existent glucose control program called GRIP (Glucose Regulation in Intensive Care patients). Before implementation of the computerized protocol, potassium replacement was physician-driven. Potassium was delivered continuously either by central venous catheter or by gastric, duodenal or jejunal tube. After every potassium measurement, nurses received a recommendation for the potassium administration rate and the time to the next measurement. In this before-after study we evaluated potassium regulation with GRIP. The attitude of the nursing staff towards potassium regulation with computer support was measured with questionnaires.</p> <p>Results</p> <p>The patient cohort consisted of 775 patients before and 1435 after the implementation of computerized potassium control. The number of patients with hypokalemia (<3.5 mmol/L) and hyperkalemia (>5.0 mmol/L) were recorded, as well as the time course of potassium levels after ICU admission. The incidence of hypokalemia and hyperkalemia was calculated. Median potassium-levels were similar in both study periods, but the level of potassium control improved: the incidence of hypokalemia decreased from 2.4% to 1.7% (P < 0.001) and hyperkalemia from 7.4% to 4.8% (P < 0.001). Nurses indicated that they considered computerized potassium control an improvement over previous practice.</p> <p>Conclusions</p> <p>Computerized potassium control, integrated with the nurse-centered GRIP program for glucose regulation, is effective and reduces the prevalence of hypo- and hyperkalemia in the ICU compared with physician-driven potassium regulation.</p

Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer

Purpose: Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study. Experimental Design: In ARMOR1, 49 patients received increasing doses (650–2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700–3,400 mg) of galeterone in tablet formulation for 12 weeks. Patients were evaluated biweekly for safety and efficacy, and pharmacokinetic parameters were assessed. Results: In ARMOR1, across all doses, 49.0% (24/49) achieved a ≥30% decline in prostate-specific antigen (PSA; PSA30) and 22.4% (11/49) demonstrated a ≥50% PSA decline (PSA50). In ARMOR2 part 1, across all doses, PSA30 was 64.0% (16/25) and PSA50 was 48.0% (12/25). In the 2,550-mg dose cohort, PSA30 was 72.7% (8/11) and PSA50 was 54.5% (6/11). Galeterone was well tolerated; the most common adverse events were fatigue, increased liver enzymes, gastrointestinal events, and pruritus. Most were mild or moderate in severity and required no action and there were no apparent mineralocorticoid excess (AME) events. Conclusions: The efficacy and safety from ARMOR1 and ARMOR2 part 1 and the pharmacokinetic results support the galeterone tablet dose of 2,550 mg/d for further study. Galeterone was well tolerated and demonstrated pharmacodynamic changes consistent with its selective, multifunctional AR signaling inhibition

Geld als water: Een onderzoek naar de strategische beleidsruimte van het Ministerie van LNV voor het combineren van natuur- en waterinvesteringen

In dit rapport wordt verslag gedaan van een onderzoek naar de strategische beleidsruimte van het Ministerie van LNV voor het inbrengen van haar belangen in en het zoeken van strategi-sche partners betreffende de reservering van ruimte voor natuurontwikkeling in andere beleidsarena's. Het gaat daarbij primair om de arena van het waterbeleid. Het onderzoek is opgehangen aan een tweetal concrete beleidsprojecten die momenteel in uitvoering zijn, te weten het Nationaal Bestuursakkoord Water en het project Ruimte voor de Rivier. Daarvoor is in eerste instantie het bestuurlijke en politieke krachtenveld rond deze projecten in kaart gebracht en worden de kansen en bedreigingen die beide projecten voor het Ministerie van LNV inhouden beschreven. Vervolgens wordt ingegaan op een aantal thema's en beleidsvel-den die voor natuur- en waterinvesteringen van belang zijn, waarna de mogelijke strategieën voor het Ministerie van LNV om te interveniëren in het gecombineerde natuur- en waterveld geanalyseerd worden. Het rapport sluit af met een aantal conclusies en aanbevelingen

Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0–2. Treatment was vinorelbine 25 mg m−2 i.v. weekly and cisplatin 100 mg m−2 i.v. every 4 weeks with hydration and standard prophylactic antiemetic treatment. Patients gave written informed consent. Characteristics of 54 consecutive patients were: males 85%, epithelial subtype 74%, IMIG stages III and IV 35 and 46%, performance status 0, 1, and 2, 26, 69, and 6%, and median age 63 years (31–78 years). CTC grade 3 or 4 toxicity occurred with respect to leukocytopenia (48% of patients, grade 4 in 13%), nausea (13%), neurotoxicity (11%), nephrotoxicity (4%), and other toxicities (9%). There were no toxic deaths. The median number of cycles was four. The fraction of patients alive at 1-, 2-, and 3-years were 61, 31, and 4%, respectively, and median survival and median time to progression were 16.8 months (0.5 to 46.4 +months) and 7.2 months (1.6 to 40.6 + months). There were two CRs and 14 PRs (response rate 29.6%). Cisplatin and intravenous vinorelbine is a highly active regimen in MPM with a response rate and survival comparable to the most active regimens so far reported

A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer: Results from Cancer and Leukemia Group B Study 90006

The use of docetaxel prolongs survival for patients with castrate resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the anti-tumor effect of docetaxel and estramustine in patients with CRPC

CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited. Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints). Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK

Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma.

Background:To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients.Methods:A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees.Results:In total, 176 MPM patients (mean age: 63.5 years+/-10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (>/=390 mg dl-1) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (</=627 mg dl-1) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months) when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl-1) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS).Conclusions:Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.British Journal of Cancer advance online publication, 16 January 2014; doi:10.1038/bjc.2013.815 www.bjcancer.com

Cancer-related fatigue: clinical practice versus practice guidelines

Purpose This study investigated adherence to treatment guidelines on cancer-related anaemia and fatigue (CRA/CRF) and factors influencing the choice of intervention. Methods In this prospective, observational study, 136 cancer patients being treated with chemotherapy in a large community hospital completed a questionnaire at consecutive outpatient visits assessing fatigue (the Functional Assessment of Chronic Illness Therapy—Fatigue) and fatigue-related counselling and advice received. Data on administration of chemotherapy and use of epoetin or blood transfusions were abstracted from the medical records. Results Fifty-three percent of patients with severe anaemia (Hb<10 g/dl) and 6% of patients with less severe anaemia (Hb levels 10-12 g/dl) received treatment (epoetin and/or blood transfusions). Half of the patients with less severe anaemia reported clinically relevant levels of fatigue. More than 50% of all patients received fatigue-related counselling, primarily at the start of chemotherapy. Most counselling was directed at energy conservation. Fatigue was not associated significantly with the use of epoetin or blood transfusion. Patients receiving palliative treatment (17%), male patients (16%) and patients with a low Hb level (<6.2 g/dl, 38%) were treated significantly more often with epoetin. Conclusions In daily clinical practice, guidelines concerning the use of epoetin or blood transfusion in severe CRA are adhered to in about half of the cases. In patients with less severe anaemia, the level of fatigue did not play a significant role in the use of epoetin. According to current guidelines, counselling on CRF should be directed primarily at activity enhancement. However, only a minority of patients receive such counselling

In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells

<p>Abstract</p> <p>Background</p> <p>Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This <it>in vitro </it>study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules.</p> <p>Methods</p> <p>The cytotoxicity, radiosensitising potential and cell cycle effect of MTA were investigated in A549 (NSCLC) and CAL-27 (SCCHN) cells. Using simultaneous or sequential exposure schedules, the cytotoxicity and radiosensitising effect of 24 h MTA combined with 1 h or 24 h dFdC were analysed.</p> <p>Results</p> <p>Including a time interval between MTA exposure and irradiation seemed favourable to MTA immediately preceding or following radiotherapy. MTA induced a significant S phase accumulation that persisted for more than 8 h after drug removal. Among different MTA/dFdC combinations tested, the highest synergistic interaction was produced by 24 h MTA followed by 1 h dFdC. Combined with irradiation, this schedule showed a clear radiosensitising effect.</p> <p>Conclusions</p> <p>Results from our <it>in vitro </it>model suggest that the sequence 24 h MTA → 1 h dFdC → RT is the most rational design and would, after confirmation in an <it>in vivo </it>setting, possibly provide the greatest benefit in the clinic.</p