Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

Clinics in diagnostic imaging (204). Gastro-gastric intussusception due to gastric gastrointestinal stromal tumour (GIST).

A 95-year-old woman presented with abdominal bloating and anorexia of one week's duration. Contrast-enhanced computed tomography (CT) revealed features in keeping with gastro-gastric intussusception with a lead mass. Oesophagogastroduodenoscopy demonstrated a large 5-cm pedunculated fundal mass intussuscepted into the distal stomach. The patient subsequently underwent endoscopic polypectomy and open gastrostomy. Histological evaluation of the gastric mass revealed a gastrointestinal stromal tumour. Her postoperative course was uneventful. We herein describe the radiological features of adult intussusception and illustrate the usefulness of CT in the detection and characterisation of lead masses.

A Novel Wind Speed Estimation Based on the Integration of an Artificial Neural Network and a Particle Filter Using BeiDou GEO Reflectometry.

Oceanographic remote sensing, which is based on the sensitivity of reflected signals from the Global Navigation Satellite Systems (GNSS), so-called GNSS-Reflectometry (GNSS-R), is very useful for the observation of ocean wind speed. Wind speed estimation over the ocean is the core factor in maritime transportation management and the study of climate change. The main concept of the GNSS-R technique is using the different times between the reflected and the direct signals to measure the wind speed and wind direction. Accordingly, this research proposes a novel technique for wind speed estimation involving the integration of an artificial neural network and the particle filter based on a theoretical model. Moreover, particle swarm optimization was applied to find the optimal weight and bias of the artificial neural network, in order to improve the accuracy of the estimation result. The observation dataset of the reflected signal information from BeiDou Geostationary Earth Orbit (GEO) satellite number 4 was used as an input for the estimation model. The data consisted of two phases with I and Q components. Two periods of BeiDou data were selected, the first period was from 3 to 8 August 2013 and the second period was from 12 to 14 August 2013, which corresponded to events from the typhoon Utor. The in situ wind speed measurement collected from the buoy station was used to validate the results. A coastal experiment was conducted at the Yangjiang site located in the South China Sea. The results show the ability of the proposed technique to estimate wind speed with a root mean square error of approximately 1.9 m/s.

Pay-for-performance as a cost-effective implementation strategy: results from a cluster randomized trial.

BACKGROUND: Pay-for-performance (P4P) has been recommended as a promising strategy to improve implementation of high-quality care. This study examined the incremental cost-effectiveness of a P4P strategy found to be highly effective in improving the implementation and effectiveness of the Adolescent Community Reinforcement Approach (A-CRA), an evidence-based treatment (EBT) for adolescent substance use disorders (SUDs). METHODS: Building on a $30 million national initiative to implement A-CRA in SUD treatment settings, urn randomization was used to assign 29 organizations and their 105 therapists and 1173 patients to one of two conditions (implementation-as-usual (IAU) control condition or IAU+P4P experimental condition). It was not possible to blind organizations, therapists, or all research staff to condition assignment. All treatment organizations and their therapists received a multifaceted implementation strategy. In addition to those IAU strategies, therapists in the IAU+P4P condition received US $50 for each month that they demonstrated competence in treatment delivery (A-CRA competence) and US $200 for each patient who received a specified number of treatment procedures and sessions found to be associated with significantly improved patient outcomes (target A-CRA). Incremental cost-effectiveness ratios (ICERs), which represent the difference between the two conditions in average cost per treatment organization divided by the corresponding average difference in effectiveness per organization, and quality-adjusted life years (QALYs) were the primary outcomes. RESULTS: At trial completion, 15 organizations were randomized to the IAU condition and 14 organizations were randomized to the IAU+P4P condition. Data from all 29 organizations were analyzed. Cluster-level analyses suggested the P4P strategy led to significantly higher average total costs compared to the IAU control condition, yet this average increase of 5% resulted in a 116% increase in the average number of months therapists demonstrated competence in treatment delivery (ICER = $333), a 325% increase in the average number of patients who received the targeted dosage of treatment (ICER = $453), and a 325% increase in the number of days of abstinence per patient in treatment (ICER = $8.134). Further supporting P4P as a cost-effective implementation strategy, the cost per QALY was only $8681 (95% confidence interval $1191-$16,171). CONCLUSION: This study provides experimental evidence supporting P4P as a cost-effective implementation strategy. TRIAL REGISTRATION: NCT01016704 .

Genomic skimming for identification of medium/highly abundant transposable elements in Arundo donax and Arundo plinii.

Transposable elements (TEs) are the most abundant genetic material for almost all eukaryotic genomes. Their effects on the host genomes range from an extensive size variation to the regulation of gene expression, altering gene function and creating new genes. Because of TEs pivotal contribute to the host genome structure and regulation, their identification and characterization provide a wealth of useful data for gaining an in-depth understanding of host genome functioning. The giant reed (Arundo donax) is a perennial rhizomatous C3 grass, octadecaploid, with an estimated nuclear genome size of 2744 Mbp. It is a promising feedstock for second-generation biofuels and biomethane production. To identify and characterize the most repetitive TEs in the genomes of A. donax and its ancestral A. plinii species, we carried out low-coverage whole genome shotgun sequencing for both species. Using a de novo repeat identification approach, 33,041 and 28,237 non-redundant repetitive sequences were identified and characterized in A. donax and A. plinii genomes, representing 37.55 and 31.68% of each genome, respectively. Comparative phylogenetic analyses, including the major TE classes identified in A. donax and A. plinii, together with rice and maize TE paralogs, were carried out to understand the evolutionary relationship of the most abundant TE classes. Highly conserved copies of RIRE1-like Ty1-Copia elements were discovered in two Arundo spp. in which they represented nearly 3% of each genomic sequence. We identified and characterized the medium/highly repetitive TEs in two unexplored polyploid genomes, thus generating useful information for the study of the genomic structure, composition, and functioning of these two non-model species. We provided a valuable resource that could be exploited in any effort aimed at sequencing and assembling these two genomes.

Cost-effectiveness of motivational intervention with significant others for patients with alcohol misuse.

AIMS: To estimate the incremental cost, cost-effectiveness and benefit-cost ratio of incorporating a significant other (SO) into motivational intervention for alcohol misuse. DESIGN: We obtained economic data from the one year with the intervention in full operation for patients in a recent randomized trial. SETTING: The underlying trial took place at a major urban hospital in the United States. PARTICIPANTS: The trial randomized 406 (68.7% male) eligible hazardous drinkers (196 during the economic study) admitted to the emergency department or trauma unit. INTERVENTION: The motivational interview condition consisted of one in-person session featuring personalized normative feedback. The significant other motivational interview condition comprised one joint session with the participant and SO in which the SO's perspective and support were elicited. MEASUREMENTS: We ascertained activities across 445 representative time segments through work sampling (including staff idle time), calculated the incremental cost in per patient of incorporating an SO, expressed the results in 2014 US$, incorporated quality and mortality effects from a closely related trial and derived the cost per quality-adjusted life-year (QALY) gained. FINDINGS: From a health system perspective, the incremental cost per patient of adding an SO was $341.09 [95% confidence interval (CI) = $244.44-437.74]. The incremental cost per year per hazardous drinker averted was $3623 (CI = $1777-22,709), the cost per QALY gained $32,200 (CI = $15,800-201,700), and the benefit-cost ratio was 4.73 (95% CI = 0.7-9.66). If adding an SO into the intervention strategy were concentrated during the hours with highest risk or in a trauma unit, it would become even more cost-beneficial. CONCLUSIONS: Using criteria established by the World Health Organization (cost-effectiveness below the country's gross domestic product per capita), incorporating a significant other into a patient's motivational intervention for alcohol misuse is highly cost-effective.

Suicide and Suicidal Attempts in the United States: Costs and Policy Implications.

The national cost of suicides and suicide attempts in the United States in 2013 was $58.4 billion based on reported numbers alone. Lost productivity (termed indirect costs) represents most (97.1%) of this cost. Adjustment for under-reporting increased the total cost to $93.5 billion or $298 per capita, 2.1-2.8 times that of previous studies. Previous research suggests that improved continuity of care would likely reduce the number of subsequent suicidal attempts following a previous nonfatal attempt. We estimate a highly favorable benefit-cost ratio of 6 to 1 for investments in additional medical, counseling, and linkage services for such patients.

The Brief Treatment Cost Analysis Tool (TCAT-Lite) for Substance Abuse Treatment: Reliability and Application.

Although several costing instruments have been previously developed, few have been validated or applied systematically to the delivery of evidence-based practices (EBPs). Using data collected from 26 organizations implementing the same EBP, this paper examined the reliability, validity, and applicability of the brief Treatment Cost Analysis Tool (TCAT-Lite). The TCAT-Lite demonstrated good reliability-correlations between replications averaged 0.61. Validity also was high, with correlation of treated episodes per $100,000 between the TCAT-Lite and independent data of 0.57. In terms of applicability, cost calculations found that if all organizations had operated at optimal scale (124 client episodes per year), existing funds could have supported 64% more clients.

Biological activity of AC3174, a peptide analog of exendin-4.

Exenatide, the active ingredient of BYETTA (exenatide injection), is an incretin mimetic that has been developed for the treatment of patients with type 2 diabetes. Exenatide binds to and activates the known GLP-1 receptor with a potency comparable to that of the mammalian incretin GLP-1(7-36), thereby acting as a glucoregulatory agent. AC3174 is an analog of exenatide with leucine substituted for methionine at position 14, [Leu(14)]exendin-4. The purpose of these studies was to evaluate the glucoregulatory activity and pharmacokinetics of AC3174. In RINm5f cell membranes, the potency of AC3174 for the displacement of [(125)I]GLP-1 and activation of adenylate cyclase was similar to that of exenatide and GLP-1. In vivo, AC3174, administered as a single IP injection, significantly decreased plasma glucose concentration and glucose excursion following the administration of an oral glucose challenge in both non-diabetic (C57BL/6) and diabetic db/db mice (P<0.05 vs. vehicle-treated). The magnitude of glucose lowering of AC3174 was comparable to exenatide. The ED(50) values of AC3174 for glucose lowering (60 minute post-dose) were 1.2 microg/kg in db/db mice and 1.3 microg/kg in C57BL/6 mice. AC3174 has insulinotropic activity in vivo. Administration of AC3174 resulted in a 4-fold increase in insulin concentrations in normal mice following an IP glucose challenge. AC3174 was also shown to inhibit food intake and decrease gastric emptying in rodent models. AC3174 was stable in human plasma (>90% of parent peptide was present after 5 h of incubation). In rats, the in vivo half-life of AC3174 was 42-43 min following SC administration. In summary, AC3174 is an analog of exenatide that binds to the GLP-1 receptor in vitro and shares many of the biological and glucoregulatory activities of exenatide and GLP-1 in vivo.