Buoyancy-Induced Convection Driven by Frontal Polymerization.

In this Letter, we study the interaction between a self-sustaining exothermic reaction front propagating in a direction perpendicular to that of gravity and the buoyancy-driven convective flow during frontal polymerization (FP) of a low-viscosity monomer resin. As the polymerization front transforms the liquid monomer into the solid polymer, the large thermal gradients associated with the propagating front sustain a natural convection of the fluid ahead of the front. The fluid convection in turn affects the reaction-diffusion (RD) dynamics and the shape of the front. Detailed multiphysics numerical analyses and particle image velocimetry experiments reveal this coupling between natural convection and frontal polymerization. The frontal Rayleigh (Ra) number affects the magnitude of the velocity field and the inclination of the front. A higher Ra number drives instability during FP, leading to the observation of thermal-chemical patterns with tunable wavelengths and magnitudes.

MRI-based tumor inter-fraction motion statistics for rectal cancer boost radiotherapy.

BACKGROUND: In patients diagnosed with rectal cancer, dose escalation is currently being investigated in a large number of studies. Since there is little known on gross tumor volume (GTV) inter-fraction motion for rectal cancer, a wide variety in margins is used. Purpose of this study is to quantify GTV inter-fraction motion statistics on different timescales and to give estimates of planning target volume (PTV) margins. MATERIAL AND METHODS: Thirty-two patients, diagnosed with rectal cancer, were included. To investigate motion from week-to-week, 16 patients underwent a pretreatment and five weekly MRIs, prior to a radiotherapy (RT) fraction of the chemoradiotherapy treatment. To investigate motion from day-to-day, the remaining 16 patients underwent five daily MRIs before each fraction in one week of RT. GTV was delineated on all scans according to guidelines. Scans were aligned on bony anatomy with the first MRI. For both datasets separately, GTV inter-fraction motion was determined based on center-of-gravity displacement. Therefrom, systematic and random errors were determined in left/right (LR), anterior/posterior and cranial/caudal (CC) direction. PTV margin estimates were calculated and evaluated on GTV coverage. RESULTS: Systematic and random errors were found in the range of 2.3-4.8 mm and 1.5-3.3 mm from week-to-week, and 1.8-4.5 mm and 1.8-4.0 mm from day-to-day, respectively. On both timescales, similar motion patterns were found; the most motion was observed in CC whilst the least motion was observed in LR. On the week-to-week data more systematic and less random motion was observed compared to the day-to-day data. Overall, only slight differences in margin estimates were found. Derived PTV margin estimates were found to give adequate GTV coverage. CONCLUSION: GTV inter-fraction motion, on a week-to-week and day-to-day timescale, can be accounted for using motion statistics presented in this study.

Analysis of the psychological impact of cancer-related symptoms on patients with non-small cell lung cancer.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience adverse physical symptoms because of cancer, cancer treatment, and comorbidities. The relations among Cancer-Related Symptoms, Functional Impairment, and Psychological Symptoms in patients with NSCLC is not well understood. METHODS: Retrospective analysis of patient-reported symptoms with the 38-item Patient Care Monitor survey, collected in routine clinical care for 1138 patients with NSCLC at eight US community oncology practices. Study sample was randomly split, and structural equation models examined the direct and mediated effects of Cancer-Related Symptoms and Functional Impairment on symptoms of acute distress (Distress) and depression (Despair) in the training sample. The training model was cross validated in testing sample. Results are presented for the full model using the entire sample. RESULTS: Patients were 48.3% female, with mean age of 66.0 years. The most common comorbidities were anemia (60.8%) and respiratory disease (24.5%). Severity of Cancer-Related Symptoms was strongly and positively related to Functional Impairment and Psychological Symptoms in both training and testing models. The modeled effect of Functional Impairment on Distress and Despair was significant in the overall model using the total sample, and significant or near-significant in the training and testing models. The mediated effect of Cancer-Related Symptoms by Functional Impairment tended to be weaker than its direct modeled effect on Distress and Despair. CONCLUSIONS: Despite prior research suggesting that Functional Impairment plays a larger role than symptom burden in depression in NSCLC, the independent modeled effects of Functional Impairment were no greater than the direct modeled effects of Cancer-Related Symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Effectiveness outcomes and health related quality of life impact of disease progression in patients with advanced nonsquamous NSCLC treated in real-world community oncology settings: results from a prospective medical record registry study.

BACKGROUND: Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line include platinum-based doublet therapy with or without bevacizumab. This study examined efficacy outcomes and patient reported outcomes (PROs) in a community oncology patient sample. METHODS: Advanced nonsquamous NSCLC patients from 34 U.S. community oncology practices treated in first line with bevacizumab regimens (A platinum doublet; gemcitabine doublet; pemetrexed with platinum) or non-bevacizumab regimens (B platinum doublet; gemcitabine doublet; C pemetrexed with platinum) were recruited for this prospective study. Patient characteristics and clinical outcomes were accessed from routine care records. Three validated and widely used PRO measures of health related quality of life (HRQOL) and symptom burden were collected prospectively at each visit and up to one-year follow-up. Effectiveness outcomes were progression free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier and Cox regression methods. PROs were analyzed with linear mixed model regression to examine changes over time, and the effect of disease progression. RESULTS: Of 147 patients in the study, 145 provided PRO data. Patients in treatment groups were: A (n = 66, 44.9%); B (n = 25, 17.0%); C (n = 56, 38.1%). A was associated with significantly longer OS than B (HR = 0.341, p = 0.0012), and significantly longer than C (HR = 0.602, p = 0.0354). PFS results were similar. Irrespective of regimen group and on 12/32 measures, patients showed significant and clinically meaningful worsening of symptoms and HRQOL at disease progression. After disease progression, the pattern of symptom and HRQOL change showed continued worsening. CONCLUSIONS: Bevacizumab-containing regimens were associated with longer PFS and OS compared with non-bevacizumab regimens. PRO measures show disease progression is associated with worsening HRQOL. Delaying disease progression can sustain better HRQL and reduce symptom burden.

Non-invasive MR assessment of macroscopic and microscopic vascular abnormalities in the rectal tumour-surrounding mesorectum.

OBJECTIVES: To evaluate the MRI macroscopic and microscopic parameters of mesorectal vasculature in rectal cancer patients. METHODS: Thirteen patients with rectal adenocarcinoma underwent a dynamic contrast-enhanced MRI at 1.5 T using a blood pool agent at the primary staging. Mesorectal macrovascular features, i.e., the number of vascular branches, average diameter and length, were assessed from baseline-subtracted post-contrast images by two independent readers. Mesorectal microvascular function was investigated by means of area under the enhancement-time curve (AUC). Histopathology served as reference standard of the tumour response to CRT. RESULTS: The average vessel branching in the mesorectum around the tumour and normal rectal wall was 8.2 ± 3.8 and 1.7 ± 1.3, respectively (reader1: p = 0.001, reader2: p = 0.002). Similarly, the tumour-surrounding mesorectum displayed circa tenfold elevated AUC (p = 0.01). Interestingly, patients with primary node involvement had a twofold higher number of macrovascular branches compared to those with healthy nodes (reader1: p = 0.005 and reader2: p = 0.03). A similar difference was observed between good and poor responders to CRT, whose tumour-surrounding mesorectum displayed 10.7 ± 3.4 and 5.6 ± 1.5 vessels, respectively (reader1/reader2: p = 0.02). CONCLUSIONS: We showed at baseline MRI of rectal tumours a significantly enhanced macrovascular structure and microvascular function in rectal tumour-surrounding mesorectum, and the association of primary mesorectal macrovascular parameters with node involvement and therapy response. KEY POINTS: • Vascular MRI reveals macrovascular and microvascular abnormalities in the rectal tumour-surrounding mesorectum. • Formation of highly vascular stroma precedes the actual tumour invasion. • High macrovascular parameters are associated with node involvement. • Mesorectal vascular network differs for good and poor responders.

Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer.

The drug fluorouracil (5-FU) is a widely used antimetabolite chemotherapy in the treatment of colorectal cancer. The gene uridine monophosphate synthetase (UMPS) is thought to be primarily responsible for conversion of 5-FU to active anticancer metabolites in tumor cells. Mutation or aberrant expression of UMPS may contribute to 5-FU resistance during treatment. We undertook a characterization of UMPS mRNA isoform expression and sequence variation in 5-FU-resistant cell lines and drug-naive or -exposed primary and metastatic tumors. We observed reciprocal differential expression of two UMPS isoforms in a colorectal cancer cell line with acquired 5-FU resistance relative to the 5-FU-sensitive cell line from which it was derived. A novel isoform arising as a consequence of exon skipping was increased in abundance in resistant cells. The underlying mechanism responsible for this shift in isoform expression was determined to be a heterozygous splice site mutation acquired in the resistant cell line. We developed sequencing and expression assays to specifically detect alternative UMPS isoforms and used these to determine that UMPS was recurrently disrupted by mutations and aberrant splicing in additional 5-FU-resistant colorectal cancer cell lines and colorectal tumors. The observed mutations, aberrant splicing and downregulation of UMPS represent novel mechanisms for acquired 5-FU resistance in colorectal cancer.

Sequential Organ Failure Assessment in H1N1 pandemic planning.

OBJECTIVE: The H1N1 pandemic has highlighted the importance of reliable and valid triage instruments. A Sequential Organ Failure Assessment score of >11 has been proposed to exclude patients from critical care resources quoting an associated mortality of >90%. We sought to assess the mortality associated with this Sequential Organ Failure Assessment threshold and the resource implications of such a triage protocol. DESIGN: Retrospective cohort. SETTING: Three multisystem intensive care units. PATIENTS: Consecutive patients admitted from January 2003 to December 2008. Subsequently, a comparison H1N1 cohort was assembled consisting of all patients admitted in 2009 with confirmed H1N1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sequential Organ Failure Assessment was collected daily by use of an electronic bedside clinical information system (n = 10,204 patients, 69,913 patient days). Mean admission Acute Physiology and Chronic Health Evaluation was 19.1. 13.4% of the cohort (9% of total patient days) had an initial Sequential Organ Failure Assessment of >11. Mortality in patients with an initial Sequential Organ Failure Assessment score of >11 was 59% (95% confidence interval: 56%, 62%). The mortality associated with an initial Sequential Organ Failure Assessment >11 across diagnostic categories varied from 29% for poisoning to 67% for neurologic patients. Hospital mortality exceeded 90% only when initial Sequential Organ Failure Assessment was >20 (0.2% of patients). H1N1 patients were younger, had a longer intensive care unit length of stay, and more commonly had a respiratory admission diagnosis than the nonH1N1 cohort. Hospital mortality in H1N1 patients with an initial Sequential Organ Failure Assessment score of >11 was 31% (95% confidence interval: 5%, 56%). CONCLUSIONS: A Sequential Organ Failure Assessment score of >11 was not associated with a hospital mortality of >90% at any time during intensive care unit stay. Only a small proportion of patients have the extreme initial Sequential Organ Failure Assessment values associated with a hospital mortality of >90% limiting the usefulness of Sequential Organ Failure Assessment as a triage instrument for pandemic planning. Application of a Sequential Organ Failure Assessment threshold of >11 to the recent H1N1 pandemic would have excluded patients with a markedly lower mortality than seen in a large regional cohort of intensive care unit patients.

Implementation of the Multidisciplinary Guideline on Chronic Pain in Vulnerable Nursing Home Residents to Improve Recognition and Treatment: A Qualitative Process Evaluation.

The recognition and treatment of pain in nursing home residents presents challenges best addressed by a multidisciplinary approach. This approach is also recommended in the applicable Dutch guideline; however, translating guidelines into practical strategies is often difficult in nursing homes. Nevertheless, a better understanding of guideline implementation is key to improving the quality of care. Here we describe and qualitatively evaluate the implementation process of the multidisciplinary guideline 'Recognition and treatment of chronic pain in vulnerable elderly' in a Dutch nursing home. The researchers used interviews and document analyses to study the nursing home's implementation of the guideline. The project team of the nursing home first filled out an implementation matrix to formulate goals based on preferred knowledge, attitudes, and behaviors for the defined target groups. Together with experts and organizations, pharmacotherapy audit meetings were organized, an expert pain team was appointed, a policy document and policy flowchart were prepared, and 'anchor personnel' were assigned to disseminate knowledge amongst professionals. Implementation was partially successful and resulted in a functioning pain team, a pain policy, the selection of preferred measurement instruments, and pain becoming a fixed topic during multidisciplinary meetings. Nevertheless, relatively few professionals were aware of the implementation process.

A contemporary assessment of devices for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): resource-specific options per level of care.

PURPOSE: Use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) as adjunct for temporary hemorrhage control in patients with exsanguinating torso hemorrhage is increasing. Characteristics of aortic occlusion balloons (AOB) are diverse and evolving as efforts are made to improve the technology. It is important to select a device that fits the requirements of the medical situation to minimize the risk of failure and complications. The aim of this study is to appraise guidance in the choice of an AOB in a specific situation. METHODS: We assessed 29 AOB for differences and outline possible advantages and disadvantages of each. Bending stiffness was measured with a three-point bending device. RESULTS: Diameter of the AOB ranged from 6 (ER-REBOA™) to 10 (Coda®-46) French. However, some need large-bore access sheaths up to 22 French (Fogarty®-45 and LeMaitre®-45) or even insertion via cut-down (Equalizer™-40). Bending stiffness varied from 0.08 N/mm (± 0.008 SD; Coda®-32) to 0.72 N/mm (± 0.024 SD; Russian prototype). Rescue Balloon™ showed kinking of the shaft at low bending pressures. The only non-compliant AOB is REBOA Balloon®. ER-REBOA™, Fogarty®, LeMaitre®, REBOA Balloon®, and Rescue Balloon™ are provided with external length marks to assist blind positioning. CONCLUSION: In resource-limited settings, a guidewire- and fluoroscopy-free, rather stiff device, such as ER-REBOA™, Fogarty®, and LeMaitre®, is warranted. Of these devices, ER-REBOA™ is the only catheter compatible with seven French sheaths and specifically designed for emergency hemorrhage control. Of the over-the-wire devices, Q50® has several features that facilitate use and reduce the risk of malplacement or vessel damage.

Thrombolysis of Postoperative Acute Pulmonary Embolism with a Thrombus in Transit.

Right heart thrombus in transit clot (RHTT) associated with a pulmonary thromboembolism (PTE) is a rare but potentially fatal diagnosis. Early diagnosis and immediate intervention are crucial. This report describes the case of a healthy, physically active 32-year-old female who presented 19 days postoperatively, following an anterior cruciate ligament reconstruction and partial lateral meniscectomy with a saddle PE, RHTT, and right ventricular (RV) strain. The patient received half of the standard dose of intravenous tissue plasminogen activator (TPA) in combination with anticoagulation and survived. Case reports of RHTT will inform future studies designed to evaluate whether and when thrombolysis should be administered.

Effect of Brain Metastasis on Patient-Reported Outcomes in Advanced NSCLC Treated in Real-World Community Oncology Settings.

INTRODUCTION: Health-related quality of life (HRQOL) in advanced non-small-cell lung cancer (NSCLC) might be affected by the presence of brain metastasis (BM). We report findings from a prospective observational study that examined HRQOL in patients newly diagnosed with advanced NSCLC, with or without baseline BM, through 1 year of follow-up. PATIENTS AND METHODS: Patients starting first-line treatment of stage IIIB/IV NSCLC were prospectively enrolled and consented at 34 US-based community oncology practices. Data on patient-reported outcomes (PROs) were collected once per cycle during treatment, and at each visit after discontinuation. PROs included the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and Lung Cancer Module (QLQ-LC13), the Lung Cancer Module of the M.D. Anderson Symptom Inventory (MDASI-LC), and the Rotterdam Activity Level Scale (RALS). Linear mixed models were used to examine the effect of baseline BM, including differences in change over time. RESULTS: One hundred forty-five patients provided follow-up PRO data, comprising 1100 individual surveys and 32 PRO end points. The patient group was 58.6% (n = 85) male, and 86.2% (n = 125) Caucasian. Patients with baseline BM were younger (61.3 vs. 65.8 years; P = .040) with more concurrent radiotherapy (59.4% [n = 19] vs. 15.9% [n = 18]; P < .0001). Results showed minimal differences in baseline HRQOL. Of the 20 measures that showed significant group differences in HRQOL over time, 18 showed greater deterioration for patients with baseline BM. These 18 measures included all QLQ-C30 composite measures except Global Health Status, all MDASI-LC measures, and the RALS (all P < .05). For these measures, the average 1-year deterioration in patients with baseline BM was 19.4%. CONCLUSION: Newly diagnosed advanced NSCLC patients with baseline BM experienced a significantly faster and clinically meaningful deterioration in PRO-based HRQOL compared with those without baseline BM.

Does setup on rectal wall improve rectal cancer boost radiotherapy?

BACKGROUND: Rectal cancer patients that show a pathological complete response (pCR) after neo-adjuvant chemo-radiotherapy, have better prognosis. To increase pCR rates several studies escalate the tumor irradiation dose. However, due to lacking tumor contrast on online imaging techniques, no direct tumor setup can be performed and large boost margins are needed to ensure tumor coverage. The purpose of this study was to evaluate the feasibility of performing a setup on rectal wall for rectal cancer boost radiotherapy, thereby using rectal wall nearby the tumor as tumor position surrogate. METHODS: For sixteen patients, daily MRI's were performed during 1 week of radiotherapy. On each of these images, tumor and rectum were delineated. Residual displacements were determined per surface voxel after setup on bony anatomy or nearby rectal wall and setup errors for both setups were compared. Furthermore for every rectal wall voxel nearby the tumor, displacement was compared with the closest tumor point and correlation was determined. RESULTS: Mean (SD) setup error was 2.7 mm (3.3 mm) and 2.2 mm (3.2 mm) after setup on bony anatomy and rectal wall respectively. Nevertheless, similar PTV-margin estimates i.e. 95th percentile distances, were found; 8.0 mm. Also, a merely moderate correlation; ρ = 0.66 was found between rectal wall and tumor displacement. Further investigation into tumor and rectal mobility differences showed that the rectal wall lacks appropriate anatomical landmarks to find true displacements, especially to capture motion along the rectal wall. CONCLUSIONS: Setup on rectal wall slightly reduces mean setup errors but requires a similar PTV-margin as compared to setup on bony anatomy. Rectal mobility might be similar to tumor mobility, but due the absence of anatomical landmarks in the rectum, displacements along the rectal wall are not detected on current online imaging. Therefore, to further reduce tumor position uncertainties, direct or indirect online tumor visualization is needed.

Innovative approach to the design and evaluation of treatment adherence interventions for drug-resistant TB.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) treatment is expensive, lengthy, and can cause severe side effects. Patients face socio-economic, psychosocial, and systemic barriers to adherence; poor adherence results in poor treatment outcomes. OBJECTIVE: To estimate the effects of the components of the information-motivation-behavioral skills model on DR-TB treatment adherence. DESIGN: We recruited 326 adults receiving DR-TB treatment and 86 of their health care service providers from 40 health centers in Lima, Peru. The main outcome was adherence (i.e., the proportion of prescribed doses taken by a patient). Exposure measures were adherence information, motivation, and behavioral skills; loss to follow-up during previous TB treatment(s); providers' work engagement; and patient-perceived support from his/her social network. RESULTS: Structural equation modeling revealed that adherence information and motivation had positive effects on adherence, but only if mediated through behavioral skills (ß = 0.02, P < 0.01 and ß = 0.07, P < 0.001, respectively). Behavioral skills had a direct positive effect on adherence (ß = 0.27, P < 0.001). Loss to follow-up during previous treatment had a direct negative effect, providers' work engagement had a direct positive effect, and perceived support had indirect positive effects on adherence. The model's overall R2 was 0.76. CONCLUSION: The components of the information-motivation-behavioral skills model were associated with adherence and could be used to design, monitor, and evaluate interventions targeting adherence to DR-TB treatment.

Effect of critical care medicine fellows on patient outcome in the intensive care unit.

BACKGROUND: The impact that physician trainees have on patient outcomes in academic adult medical/surgical intensive care units (ICUs) has not been adequately assessed. METHOD: All admissions to adult ICUs within the Calgary Health Region over a three-year period when a critical care medicine fellow (CCMF) was on service were compared to when an attending physician was alone on service. Primary outcomes were ICU and in-hospital mortality and length of stay (LOS). RESULTS: CCMFs and attending physicians admitted 3,341 patients, while attending physicians alone admitted 3,224 patients. There was no difference in ICU or in-hospital mortality between the two groups; regression analysis determined CCMFs did not affect patient LOS. CONCLUSION: In teaching hospitals with adult mixed medical/surgical ICUs, CCMFs do not have an effect on patient outcome or LOS. Improved patient outcomes at academic institutions previously attributed to the presence of CCMFs may instead be due to institution and patient-related factors.

Positive illusions in marital relationships: a 13-year longitudinal study.

This study examined the long-term consequences of idealization in marriage, using both daily diary and questionnaire data collected from a sample of 168 newlywed couples who participated in a 4-wave, 13-year longitudinal study of marriage. Idealization was operationalized as the tendency for people to perceive their partner as more agreeable than would be expected based on their reports of their partner's agreeable and disagreeable behaviors. Spouses who idealized one another were more in love with each other as newlyweds. Longitudinal analyses suggested that spouses were less likely to suffer declines in love when they idealized one another as newlyweds. Newlywed levels of idealization did not predict divorce.

Evolution of motion uncertainty in rectal cancer: implications for adaptive radiotherapy.

Reduction of motion uncertainty by applying adaptive radiotherapy strategies depends largely on the temporal behavior of this motion. To fully optimize adaptive strategies, insight into target motion is needed. The purpose of this study was to analyze stability and evolution in time of motion uncertainty of both the gross tumor volume (GTV) and clinical target volume (CTV) for patients with rectal cancer. We scanned 16 patients daily during one week, on a 1.5 T MRI scanner in treatment position, prior to each radiotherapy fraction. Single slice sagittal cine MRIs were made at the beginning, middle, and end of each scan session, for one minute at 2 Hz temporal resolution. GTV and CTV motion were determined by registering a delineated reference frame to time-points later in time. The 95th percentile of observed motion (dist95%) was taken as a measure of motion. The stability of motion in time was evaluated within each cine-MRI separately. The evolution of motion was investigated between the reference frame and the cine-MRIs of a single scan session and between the reference frame and the cine-MRIs of several days later in the course of treatment. This observed motion was then converted into a PTV-margin estimate. Within a one minute cine-MRI scan, motion was found to be stable and small. Independent of the time-point within the scan session, the average dist95% remains below 3.6 mm and 2.3 mm for CTV and GTV, respectively 90% of the time. We found similar motion over time intervals from 18 min to 4 days. When reducing the time interval from 18 min to 1 min, a large reduction in motion uncertainty is observed. A reduction in motion uncertainty, and thus the PTV-margin estimate, of 71% and 75% for CTV and tumor was observed, respectively. Time intervals of 15 and 30 s yield no further reduction in motion uncertainty compared to a 1 min time interval.

Is regional citrate superior to systemic heparin anticoagulation for continuous renal replacement therapy? A prospective observational study in an adult regional critical care system.

PURPOSE: Continuous renal replacement therapy (CRRT) is commonly used in the care of critically ill patients although the optimal means of anticoagulation is not well defined. We report our regional CRRT protocol that was developed using the principles of quality improvement and compare the effect of regional citrate with systemic heparin anticoagulation on filter life span. MATERIALS AND METHODS: Prospective observational cohort study in a Canadian adult regional critical care system. A standardized protocol for CRRT has been implemented at all adult intensive care units in the Calgary Health Region since August 1999. All patients with acute renal failure treated with CRRT during October 1, 2002, to September 30, 2003, were identified and followed up prospectively until hospital discharge or death. RESULTS: Eighty-seven patients with acute renal failure requiring CRRT were identified, 54 were initially treated with citrate, 29 with heparin, and 4 with saline flushes. Citrate and heparin were used in 212 (66%) and 97 (30%) of filters for 8776 and 2651 hours of CRRT, respectively. Overall median (interquartile range) filter life span with citrate was significantly greater than heparin (40 [14-72] vs 20 [5-44] hours, P < .001). The median time to spontaneous filter failure was significantly greater with citrate compared with heparin (>72 vs 33 hours, P < .001). Citrate anticoagulation resulted in greater completion of scheduled filter life span (59% vs 10%, P > .001). Citrate anticoagulation was well tolerated with no patient requiring elective discontinuation for hypernatremia, metabolic alkalosis, or hypocalcemia. CONCLUSIONS: Regional citrate anticoagulation was associated with prolonged filter survival and increased completion of scheduled filter life span compared with heparin. These data support small studies suggesting that citrate is a superior anticoagulant for CRRT and suggest the need for a future definitive randomized controlled trial.

Treatment Patterns and Health Resource Utilization Among Patients Diagnosed With Early Stage Resected Non-Small Cell Lung Cancer at US Community Oncology Practices.

UNLABELLED: Data on adjuvant therapy in resected non-small cell lung cancer (NSCLC) in routine practice are lacking in the United States. This retrospective observational database study included 609 community oncology patients with resected stage IB to IIIA NSCLC. Use of adjuvant therapy was 39.1% at disease stage IB and 64.9% to 68.2% at stage II to IIIA. The most common regimen at all stages was carboplatin and paclitaxel. BACKGROUND: Platin-based adjuvant chemotherapy has extended survival in clinical trials in patients with completely resected non-small cell lung cancer (NSCLC). There are few data on the use of adjuvant therapy in community-based clinical practice in the United States. MATERIALS AND METHODS: This was a retrospective observational study using electronic medical record and billing data collected during routine care at US community oncology sites in the Vector Oncology Data Warehouse between January 2007 and January 2014. Patients aged ≥ 18 years with a primary diagnosis of stage IB to IIIA NSCLC were eligible if they had undergone surgical resection. Treatment patterns, health care resource use, and cost were recorded, stratified by stage at diagnosis. RESULTS: The study included 609 patients (mean age, 64.8 years, 52.9% male), of whom 215 had stage IB disease, 130 stage IIA/II, 110 stage IIB, and 154 stage IIIA. Adjuvant systemic therapy after resection was provided to 345 (56.7%) of 609 patients, with lower use in patients with stage IB disease (39.1%) than stage II to IIIA disease (64.9-68.2%) (P < .0001). The most common adjuvant regimen at all stages was the combination of carboplatin and paclitaxel. There were no statistically significant differences in office visits or incidence of hospitalization by disease stage. During adjuvant treatment, the total monthly median cost per patient was $17,389.75 (interquartile range, $8,815.61 to $23,360.85). CONCLUSION: Adjuvant systemic therapy was used in some patients with stage IB NSCLC and in the majority of patients with stage IIA to IIIA disease. There were few differences in regimen or health care resource use by disease stage.

RandomizEd controlled trial for pre-operAtive dose-escaLation BOOST in locally advanced rectal cancer (RECTAL BOOST study): study protocol for a randomized controlled trial.

BACKGROUND: Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT). METHODS/DESIGN: This study follows the 'cohort multiple randomized controlled trial' (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients-histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ≤10 cm from the anorectal transition who provided consent for experimental intervention offers-form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed. sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3-4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat. DISCUSSION: The boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability. TRIAL REGISTRATION: The Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521 . Registered 18 September 2013.

Accuracy of administrative data for assessing outcomes after knee replacement surgery.

OBJECTIVE: To assess the accuracy of information in an administrative database (Canadian Institute for Health Information; CIHI) compared with the hospital record for patients undergoing knee replacement (KR). METHODS: A stratified random sample of 185 KR recipients from 5 Ontario hospitals were chosen. Their hospital records and corresponding CIHI files were compared to assess percent complete agreement, false negative (FN) and false positive (FP) rates for demographic data, procedures, and diagnoses. RESULTS: Of 185 records, 175 (95%) were reviewed. Percent complete agreement was greater than 94% for each of patient demographics and procedures (mean FN rates: 0%; mean FP rates: 0-5%). For comorbidities and complications, although mean percent complete agreement was high, and FP rates were low, mean FN rates were 63% for specific comorbid conditions and 70% for organ systems. CONCLUSIONS: High FN rates have been found in documentation of comorbidities and in-hospital complications for CIHI data compared with the hospital record. Under-coding of comorbidities and in-hospital complications has potential implications for researchers using administrative databases.