Comparative effectiveness of denosumab, teriparatide, and zoledronic acid among frail older adults: a retrospective cohort study.

The comparative effects of zoledronic acid, denosumab, and teriparatide for preventing hip fractures in frail older adults, especially those in nursing homes, were unknown. We found that denosumab and zoledronic acid may be as effective as teriparatide for hip fracture prevention in nursing home residents. INTRODUCTION: Several non-oral drugs exist for osteoporosis treatment, including zoledronic acid (ZA), denosumab, and teriparatide. Little data exist on the comparative effectiveness of these drugs for hip fracture prevention in frail older adults. We examined their comparative effectiveness in one of the frailest segments of the US population-nursing home (NH) residents. METHODS: We conducted a national retrospective cohort study of NH residents aged ≥ 65 years using 2012 to 2016 national US Minimum Data Set clinical assessment data and linked Medicare claims. New parenteral ZA, denosumab, and teriparatide use was assessed via Medicare Parts B and D; hip fracture outcomes via Part A; and 125 covariates for confounding adjustment via several datasets. We used inverse probability weighted (IPW) competing risk regression models to compare hip fracture risk between groups with teriparatide as the reference. RESULTS: The study cohort (N = 2019) included 1046 denosumab, 578 teriparatide, and 395 ZA initiators. Mean age was 85 years, 90% were female, and 68% had at least moderate functional impairment. Seventy-two residents (3.6%) had a hip fracture and 1100 (54.5%) died over a mean follow-up of 1.5 years. Compared to teriparatide use, denosumab use was associated with a 46% lower risk of hip fracture (HR 0.54, 95% CI 0.29-1.00) and no difference was observed for ZA (HR 0.70, 95% CI 0.26-1.85). CONCLUSIONS: Denosumab and ZA may be as effective as teriparatide for hip fracture prevention in frail older adults. Given their lower cost and easier administration, denosumab and ZA are likely preferable non-oral treatments for most frail, older adults.

Peri-operative COVID-19 infection in urgent elective surgery during a pandemic surge period: a retrospective observational cohort study.

Maintaining safe elective surgical activity during the global coronavirus disease 2019 (COVID-19) pandemic is challenging and it is not clear how COVID-19 may impact peri-operative morbidity and mortality in this population. Therefore, adaptations to normal care pathways are required. Here, we establish if implementation of a bespoke peri-operative care bundle for urgent elective surgery during a pandemic surge period can deliver a low COVID-19-associated complication profile. We present a single-centre retrospective cohort study from a tertiary care hospital of patients planned for urgent elective surgery during the initial COVID-19 surge in the UK between 29 March and 12 June 2020. Patients asymptomatic for COVID-19 were screened by oronasal swab and chest imaging (chest X-ray or computed tomography if aged ≥ 18 years), proceeding to surgery if negative. COVID-19 positive patients at screening were delayed. Postoperatively, patients transitioning to COVID-19 positive status by reverse transcriptase polymerase chain reaction testing were identified by an in-house tracking system and monitored for complications and death within 30 days of surgery. Out of 557 patients referred for surgery (230 (41.3%) women; median (IQR [range]) age 61 (48-72 [1-89])), 535 patients (96%) had COVID-19 screening, of which 13 were positive (2.4%, 95%CI 1.4-4.1%). Out of 512 patients subsequently undergoing surgery, 7 (1.4%) developed COVID-19 positive status (1.4%, 95%CI 0.7-2.8%) with one COVID-19-related death (0.2%, 95%CI 0.0-1.1%) within 30 days. Out of these seven patients, four developed pneumonia, of which two required invasive ventilation including one patient with acute respiratory distress syndrome. Low rates of COVID-19 infection and mortality in the elective surgical population can be achieved within a targeted care bundle. This should provide reassurance that elective surgery can continue, where possible, despite high community rates of COVID-19.

Genetic correlations of milk fatty acid contents predicted from milk mid-infrared spectra in New Zealand dairy cattle.

The objective of this study was to estimate genetic correlations among milk fatty acid (FA) concentrations in New Zealand dairy cattle. Concentrations of each of the most common FA, expressed as a percentage of the total FA, were determined by gas chromatography on a specific cohort of animals. Using this data set, prediction equations were derived using mid-infrared (MIR) spectroscopy data collected from the same samples. These prediction equations were applied to a large data set of MIR measurements in 34,141 milk samples from 3,445 Holstein-Friesian, 2,935 Jersey, and 3,609 crossbred Holstein-Friesian × Jersey cows, sampled an average of 3.42 times during the 2007-2008 season. Data were analyzed using univariate and bivariate repeatability animal models. Heritability of predicted FA concentration in milk fat ranged from 0.21 to 0.42, indicating that genetic selection could be used to change the FA composition of milk. The de novo synthesized FA (C6:0, C8:0, C10:0, C12:0, and C14:0) showed strong positive genetic correlations with each other, ranging from 0.24 to 0.99. Saturated FA were negatively correlated with unsaturated (-0.93) and polyunsaturated (-0.84) FA. The saturated FA were positively correlated with milk fat yield and fat percentage, whereas the unsaturated FA were negatively associated with fat yield and fat percentage. Our results indicate that bovine milk FA composition can be changed through genetic selection using MIR as a phenotypic proxy.

Uptake and virological outcomes of single- versus multi-tablet antiretroviral regimens among treatment-naïve youth in the HIV Research Network.

OBJECTIVES: Several single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV). METHODS: A retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS (< 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year. RESULTS: Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P < 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/µL (AOR 1.94; 95% CI 1.18-3.19) and > 500 cells/µL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28]. CONCLUSIONS: Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.

Bayesian model of disease progression in GNE myopathy.

One Sentence Summary: A Bayesian repeated measures model based on quantitative muscle strength data from a prospective Natural History Study was developed to determine disease progression and design clinical trials for GNE myopathy, a rare and slowly progressive muscle disease. GNE myopathy is a rare muscle disease characterized by slowly progressive weakness and atrophy of skeletal muscles. To address the significant challenges of defining the natural history and designing clinical trials for GNE myopathy, we developed a Bayesian latent variable repeated measures model to determine disease progression. The model is based on longitudinal quantitative muscle strength data collected as part of a prospective Natural History Study. The GNE Myopathy Progression Model provides an understanding of disease progression that would have otherwise required a natural history of unfeasible duration. "Disease age," the model-generated measure of disease progression, highly correlates with a variety of clinical, functional and patient-reported outcomes. With the incorporation of a treatment effect parameter to the GNE Disease Progression Model, we describe a novel GNE Myopathy Disease Modification Analysis that significantly increases power and reduces the number of subjects required to test the effectiveness of novel therapies when compared to more traditional analysis methods. The GNE Myopathy Disease Progression Model and Disease Modification Analysis can be applied to muscle diseases with prospectively collected muscle strength data, and a variety of rare and slowly progressive diseases.

Widespread prevalence of a CREBRF variant amongst Maori and Pacific children is associated with weight and height in early childhood.

OBJECTIVE: Investigating a large and ethnically diverse cohort from the Pacific region, we aimed to replicate and extend the recently reported findings that a CREBRF genetic variant is strongly associated with body mass index in Samoans. METHODS: A birth cohort of more than six thousand children was utilised. In this study, genotyping of two markers (rs12513649 and rs373863828) was undertaken in Maori, Pacific, European and Asian individuals in the cohort. RESULTS: We report that these CREBRF genetic variants are not confined to Samoans but are prevalent in all other Pacific populations sampled, including Maori. We found that the rs373863828 variant was significantly associated with growth at 4 years of age. On average, we observed allele-specific increases in weight (P=0·004, +455 g, s.e. 0.158), height (P=0·007, +0·70 cm, s.e. 0.26) and waist circumference (P=0·004, +0·70 cm, s.e. 0.24) at 4 years of age. The rs373863828 variant was not associated with birth weight (P=0·129). CONCLUSIONS: We replicated the finding that a CREBRF variant is associated with increased body mass. We then built on the original findings by demonstrating the prevalence of the rs12513649 and rs373863828 variants in multiple Pacific population groups and by demonstrating that the rs373863828 variant is associated with growth in early childhood. Pacific population groups experience a disproportionately high burden of obesity, starting in early childhood. This new knowledge offers potential for evidence-based interventions aimed at establishing healthy growth trajectories from the earliest possible age.

Premorbid social adjustment and association with attenuated psychotic symptoms in clinical high-risk and help-seeking youth.

BACKGROUND: Attenuated positive symptom syndrome (APSS), characterized by 'putatively prodromal' attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of 'true' prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals. METHOD: Association between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis. RESULTS: Premorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria. CONCLUSIONS: Predictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals.

Defining hip fracture with claims data: outpatient and provider claims matter.

Medicare claims are commonly used to identify hip fractures, but there is no universally accepted definition. We found that a definition using inpatient claims identified fewer fractures than a definition including outpatient and provider claims. Few additional fractures were identified by including inconsistent diagnostic and procedural codes at contiguous sites. INTRODUCTION: Medicare claims data is commonly used in research studies to identify hip fractures, but there is no universally accepted definition of fracture. Our purpose was to describe potential misclassification when hip fractures are defined using Medicare Part A (inpatient) claims without considering Part B (outpatient and provider) claims and when inconsistent diagnostic and procedural codes occur at contiguous fracture sites (e.g., femoral shaft or pelvic). METHODS: Participants included all long-stay nursing home residents enrolled in Medicare Parts A and B fee-for-service between 1/1/2008 and 12/31/2009 with follow-up through 12/31/2011. We compared the number of hip fractures identified using only Part A claims to (1) Part A plus Part B claims and (2) Part A and Part B claims plus discordant codes at contiguous fracture sites. RESULTS: Among 1,257,279 long-stay residents, 40,932 (3.2%) met the definition of hip fracture using Part A claims, and 41,687 residents (3.3%) met the definition using Part B claims. 4566 hip fractures identified using Part B claims would not have been captured using Part A claims. An additional 227 hip fractures were identified after considering contiguous fracture sites. CONCLUSIONS: When ascertaining hip fractures, a definition using outpatient and provider claims identified 11% more fractures than a definition with only inpatient claims. Future studies should publish their definition of fracture and specify if diagnostic codes from contiguous fracture sites were used.

The predictive effect of primary tumour location in the treatment of metastatic colorectal cancer: a Canadian consensus statement.

In recently published data, the predictive value of primary tumour location for the treatment of metastatic colorectal cancer with available biologic therapies has been explored. Recognizing the potential effect of those data on clinical practice, we convened a meeting of Canadian experts who treat metastatic colorectal cancer to develop a set of national, evidence-based treatment guidelines based on primary tumour location. This report summarizes the relevant evidence and presents the consensus recommendations of those experts.

Randomized phase II study of modified FOLFOX-6 in combination with ramucirumab or icrucumab as second-line therapy in patients with metastatic colorectal cancer after disease progression on first-line irinotecan-based therapy.

BACKGROUND: Icrucumab and ramucirumab are recombinant human IgG1 monoclonal antibodies that bind VEGF receptors 1 and 2 (VEGFR-1 and -2), respectively. This randomized phase II study evaluated the antitumor activity and safety of icrucumab and ramucirumab each in combination with mFOLFOX-6 in patients with metastatic colorectal cancer after disease progression on first-line therapy with a fluoropyrimidine and irinotecan. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive mFOLFOX-6 alone (mFOLFOX-6) or in combination with ramucirumab 8 mg/kg IV (RAM+mFOLFOX-6) or icrucumab 15 mg/kg IV (ICR+mFOLFOX-6) every 2 weeks. Randomization was stratified by prior bevacizumab therapy. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, safety, and PK. RESULTS: In total, 158 patients were randomized, but only 153 received treatment (49 on mFOLFOX-6, 52 on RAM+mFOLFOX-6, and 52 on ICR+mFOLFOX-6). Median PFS was 18.4 weeks on mFOLFOX-6, 21.4 weeks on RAM+mFOLFOX-6, and 15.9 weeks on ICR+mFOLFOX-6 (RAM+mFOLFOX-6 versus mFOLFOX-6, stratified hazard ratio [HR] 1.116 [95% CI 0.713-1.745], P = 0.623; ICR+mFOLFOX-6 versus mFOLFOX-6, stratified HR 1.603 [95% CI 1.011-2.543], P = 0.044). Median survival was 53.6 weeks on mFOLFOX-6, 41.7 weeks on RAM+mFOLFOX-6, and 42.0 weeks on ICR+mFOLFOX-6. The most frequent adverse events reported on the ramucirumab arm (RAM+mFOLFOX-6) were fatigue, nausea, and peripheral sensory neuropathy; those on the icrucumab arm (ICR+mFOLFOX-6) were fatigue, diarrhea, and peripheral sensory neuropathy. Grade ≥3 serious adverse events occurred at comparable frequency across arms. CONCLUSIONS: In this study population, combining ramucirumab or icrucumab with mFOLFOX-6 did not achieve the predetermined improvement in PFS. CLINICALTRIALSGOV: NCT01111604.

Glutamine and hyperammonemic crises in patients with urea cycle disorders.

UNLABELLED: Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. METHODS: The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. RESULTS: The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8-29%) as compared with 56% (28%-154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >900 µmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2]µmol/L) than patients with baseline glutamine ≤ 900 µmol/L (26.6 [18.0]µmol/L). Glutamine values >900 µmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR]=1.98; p=0.173). However, glutamine lost predictive significance (OR=1.47; p=0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥ 1.0 upper limit of normal (ULN) was highly statistically significant (OR=4.96; p=0.013). There was no significant effect of glutamine >900 µmol/L on time to first HAC crisis (hazard ratio [HR]=1.14; p=0.813), but there was a significant effect of baseline ammonia ≥ 1.0 ULN (HR=4.62; p=0.0011). CONCLUSIONS: The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels.

Thirty-day hospital readmissions for adults with and without HIV infection.

OBJECTIVES: Risk-adjusted 30-day hospital readmission rate is a commonly used benchmark for hospital quality of care and for Medicare reimbursement. Persons living with HIV (PLWH) may have high readmission rates. This study compared 30-day readmission rates by HIV status in a multi-state sample with planned subgroup comparisons by insurance and diagnostic categories. METHODS: Data for all acute care, nonmilitary hospitalizations in nine states in 2011 were obtained from the Healthcare Costs and Utilization Project. The primary outcome was readmission for any cause within 30 days of hospital discharge. Factors associated with readmission were evaluated using multivariate logistic regression. RESULTS: A total of 5 484 245 persons, including 33 556 (0.6%) PLWH, had a total of 6 441 695 index hospitalizations, including 45 382 (0.7%) among PLWH. Unadjusted readmission rates for hospitalizations of HIV-uninfected persons and PLWH were 11.2% [95% confidence interval (CI) 11.2, 11.2%] and 19.7% (95% CI 19.3, 20.0%), respectively. After adjustment for age, gender, race, insurance, and diagnostic category, HIV infection was associated with 1.50 (95% CI 1.46, 1.54) times higher odds of readmission. Predicted, adjusted readmission rates were higher for PLWH within every insurance category, including Medicaid [12.9% (95% CI 12.8, 13.0%) and 19.1% (95% CI 18.4, 19.7%) for HIV-uninfected persons and PLWH, respectively] and Medicare [13.2% (95% CI 13.1, 13.3%) and 18.0% (95% CI 17.4, 18.7%), respectively], and within every diagnostic category. CONCLUSIONS: HIV infection is associated with significantly increased readmission risk independent of demographics, insurance, and diagnostic category. The 19.7% 30-day readmission rate may serve as a preliminary benchmark for assessing quality of care of PLWH. Policy-makers may consider adjusting for HIV infection when calculating a hospital's expected readmission rate.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Continuous versus intermittent chemotherapy strategies in metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: An important goal of intermittent strategies of delivering systemic treatment as first-line treatment of metastatic colorectal cancer (mCRC) is to maintain efficacy while improving patients' quality of life (QoL). Given the varying impact on efficacy demonstrated in individual randomized, controlled trials (RCTs), a systematic review and meta-analysis of RCTs of these intermittent strategies was carried out. DESIGN: Relevant databases were systematically searched for the period 2000-2014. RCTs that compared a continuous versus intermittent strategy of delivering systemic treatment were identified by a systematic review. Overall survival (OS) hazard ratios (HRs) were extracted from the most recently reported trial results. The results of identified trials were clinically homogeneous so the data were pooled using Review Manager software (RevMan 5.1). RESULTS: Eleven RCTs were identified (n = 4 854). For the eight (n = 4508) trials with available HRs, the treatment patients received after induction was: none (five trials, n = 3036), fluoropyrimidine (one trial, n = 620), and biologic (two trials, n = 852). There were no statistically significant survival differences observed between the continuous and intermittent chemotherapy strategies. There was no statistically significant difference observed between continuous and intermittent strategies [HR = 1.03, 95% confidence interval (CI) 0.96-1.10, P = 0.38)]. Subgroup analyses demonstrated results were generally robust across induction and maintenance regimens. One subgroup analysis of the three trials (CAIRO3, OPTIMOX2, COIN, n = 2403) with combination treatment induction and no maintenance until progression revealed a statistically, but nonclinically significant benefit for continuous treatment (HR = 1.10, 95% CI 1.00-1.20, P = 0.049). QoL life was either the same in both arms in two trials (n = 912) or improved in the intermittent strategy arm in one trial (n = 1630). CONCLUSION: Intermittent strategies of delivering systemic treatment of mCRC do not result in a clinically significant reduction in OS compared with a continuous strategy of delivery, and should be part of an informed discussion of treatment options with patients with mCRC.

Accumulation of silver by Fucus spp. (Phaeophyceae) and its toxicity to Fucus ceranoides under different salinity regimes.

Metals constitute an important group of abiotic stressors that elicit stress responses in marine algae that include the production of reactive oxygen species (ROS). Silver (Ag) is a highly toxic metal to organisms but despite this there are relatively few studies on how it affects marine macroalgae (seaweeds). In a landmark study published in 1977 the first information was provided on the accumulation of Ag in Fucus spp. (Phaeophyceae) from the Looe estuary, located in south-west England, an area with a long history of mining activity. In the present study, the estuary has been re-visited and the patterns of Ag accumulation in two Fucus spp. and sediment re-examined after 35 years. We conclude that Ag concentrations in sediment and macroalgae from specific sites within the catchment remain high, but more generally sediment concentrations have declined by approximately 65 % and the dissolved, bioavailable fraction by 24 % over this period. In addition, from laboratory studies we provide data on the speciation and toxic effects of Ag under different salinity regimes in the euryhaline brown seaweed, Fucus ceranoides. From these exposure experiments, it was found that with increasing Ag concentrations growth was inhibited and lipid peroxidation associated with ROS production increased. The magnitude of the toxic effects was greater at a salinity of 10 than 28 psu which reflects the greater bioavailability of the toxic species of Ag (Ag(+) and AgCl(0)) at reduced salinities. These findings emphasise the importance of investigating the effects of metal pollution in conjunction with other, natural, environmental stressors such as salinity.

An evidence-based approach to the management of snoring in adults.

BACKGROUND: Snoring is frequently encountered by the otolaryngologist. Given its significant impact on quality of life and that it is a symptom of sleep-related breathing disorders, diagnosis and treatment are of major importance. In particular, the diagnosis should aim to distinguish between simple snoring and obstructive sleep apnoea. This article aims to provide a systematic, concise and evidence-based method of managing the adult patient with snoring. METHOD: This review was based on a literature search last undertaken on 30 June 2014. The MEDLINE, EMBASE and Cochrane databases were searched using the subject headings snoring and obstructive sleep apnoea in adults in combination with classification, diagnosis, investigations, management, treatment and surgery. Results were limited to English language articles including case series, clinical trials, randomised controlled trials, meta-analyses, systematic reviews and review articles. Relevant references from selected articles were also reviewed. RESULTS: The majority of published literature for snoring is of level II/III evidence and that for obstructive sleep apnoea being of level I/II, with 36 relevant randomised controlled trials identified. The diagnosis of obstructive sleep apnoea involves thorough clinical assessment and typically a sleep study. Snoring may be managed with lifestyle modification, intra-oral devices or by surgical intervention, with continuous positive airway pressure being the treatment of choice for moderate-to-severe obstructive sleep apnoea. CONCLUSIONS: A structured history of snoring and its associated symptoms, comprehensive examination including flexible laryngoscopy and sleep studies where relevant, in addition to targeted investigations, should lead to the correct diagnosis and appropriate management.

Consensus statement: the 16th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Saskatoon, Saskatchewan; September 5-6, 2014.

The 16th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, September 4-5, 2014. The Consensus Conference is an interactive, multidisciplinary event attended by health care professionals from across western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

Fluence and polarisation dependence of GaAs based Lateral Photo-Dember terahertz emitters.

We characterise THz output of lateral photo-Dember (LPD) emitters based on semi-insulating (SI), unannealed and annealed low temperature grown (LTG) GaAs. Saturation of THz pulse power with optical fluence is observed, with unannealed LTG GaAs showing highest saturation fluence at 1.1 ± 0.1 mJ cm(-2). SI-GaAs LPD emitters show a flip in signal polarity with optical fluence that is attributed to THz emission from the metal-semiconductor contact. Variation in optical polarisation affects THz pulse power that is attributed to a local optical excitation near the metal contact.

A metamolecule antenna for coplanar waveguides.

We report on a metamolecule antenna, based on a fish-scale design but augmented with two split-ring resonators (SRRs) placed within the fish-scale loops. The properties of the antenna resonator, with and without additional SRRs, were examined using finite element method simulations (COMSOL Multiphysics). The simulation findings were subsequently confirmed experimentally, using a vector network analyser coupled to an antenna-loaded coplanar waveguide (CPW). The addition of SRRs to the fish-scale meta-molecule leads to a demonstrably large increase in microwave-absorption. It is shown that the fish-scale/SRR/CPW combination performs as a microwave antenna. Simulations of the antenna gain and far-field emission are presented and discussed.

Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5).

AIMS: AWARD-5 was an adaptive, seamless, double-blind study comparing dulaglutide, a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist, with placebo at 26 weeks and sitagliptin up to 104 weeks. The study also included a dose-finding portion whose results are presented here. METHODS: Type 2 diabetes (T2D) patients on metformin were randomized 3 : 1 : 1 to seven dulaglutide doses, sitagliptin (100 mg), or placebo. A Bayesian algorithm was used for randomization and dose selection. Patients were adaptively randomized to dulaglutide doses using available data on the basis of a clinical utility index (CUI) of glycosylated haemoglobin A1c (HbA1c) versus sitagliptin at 52 weeks and weight, pulse rate (PR) and diastolic blood pressure (DBP) versus placebo at 26 weeks. The algorithm randomly assigned patients until two doses were selected. RESULTS: Dulaglutide 1.5 mg was determined to be the optimal dose. Dulaglutide 0.75 mg met criteria for the second dose. Dulaglutide 1.5 mg showed the greatest Bayesian mean change from baseline (95% credible interval) in HbA1c versus sitagliptin at 52 weeks -0.63 (-0.98 to -0.20)%. Dulaglutide 2.0 mg showed the greatest placebo-adjusted mean change in weight [-1.99 (-2.88 to -1.20) kg] and in PR [0.78 (-2.10 to 3.80) bpm]. Dulaglutide 1.5 mg showed the greatest placebo-adjusted mean change in DBP [-0.62 (-3.40 to 2.30) mmHg]. CONCLUSIONS: The Bayesian algorithm allowed for an efficient exploration of a large number of doses and selected dulaglutide doses of 1.5 and 0.75 mg for further investigation in this trial.