A Short Report Examining the Introduction of Routine Use of Patient-Reported Outcome Measures in a Mixed Oncology Population.

AIMS: People living with treatable but not curable cancer often experience a range of symptoms related to their cancer and its treatment. During the COVID-19 pandemic, face-to-face consultations were reduced and so remote monitoring of these needs was necessary. University Hospitals Sussex implemented the routine use of electronic remote patient-reported outcome measures (PROMs) in a mixed oncology population, focusing on those with treatable but not curable cancers. MATERIALS AND METHODS: Over a 9-month period, patients were invited to register with My Clinical Outcomes (MCO) - a secure online platform for the collection of electronic PROMs. They were prompted by e-mail to complete assessments (EORTC QLQ-C30, EQ-5D-3L and EQ-5D VAS) routinely every 2 weeks. The team monitored patient scores and changes in these prompted clinical interventions. RESULTS: In total, 324 patients completed at least one assessment. The median number of assessments completed by each patient was eight. The most represented tumour groups were secondary breast (28%), prostate (25%) and other (32%). Median scores for the assessments did not deteriorate in a clinically or numerically significant way for patients living with non-curable conditions for the majority of patients monitored. CONCLUSION: Routine collection of electronic remote PROMs is an effective and useful strategy to provide real-time clinical feedback to teams. With integration into existing systems, online platforms (such as MCO) could provide efficient and patient-centred information for those providing care for people with cancer.

Early COVID-19 pandemic modeling: Three compartmental model case studies from Texas, USA.

The novel coronavirus (SARS-CoV-2) emerged in late 2019 and spread globally in early 2020. Initial reports suggested the associated disease, COVID-19, produced rapid epidemic growth and caused high mortality. As the virus sparked local epidemics in new communities, health systems and policy makers were forced to make decisions with limited information about the spread of the disease. We developed a compartmental model to project COVID-19 healthcare demands that combined information regarding SARS-CoV-2 transmission dynamics from international reports with local COVID-19 hospital census data to support response efforts in three Metropolitan Statistical Areas (MSAs) in Texas, USA: Austin-Round Rock, Houston-The Woodlands-Sugar Land, and Beaumont-Port Arthur. Our model projects that strict stay-home orders and other social distancing measures could suppress the spread of the pandemic. Our capacity to provide rapid decision-support in response to emerging threats depends on access to data, validated modeling approaches, careful uncertainty quantification, and adequate computational resources.

An evaluation of DistillerSR's machine learning-based prioritization tool for title/abstract screening - impact on reviewer-relevant outcomes.

BACKGROUND: Systematic reviews often require substantial resources, partially due to the large number of records identified during searching. Although artificial intelligence may not be ready to fully replace human reviewers, it may accelerate and reduce the screening burden. Using DistillerSR (May 2020 release), we evaluated the performance of the prioritization simulation tool to determine the reduction in screening burden and time savings. METHODS: Using a true recall @ 95%, response sets from 10 completed systematic reviews were used to evaluate: (i) the reduction of screening burden; (ii) the accuracy of the prioritization algorithm; and (iii) the hours saved when a modified screening approach was implemented. To account for variation in the simulations, and to introduce randomness (through shuffling the references), 10 simulations were run for each review. Means, standard deviations, medians and interquartile ranges (IQR) are presented. RESULTS: Among the 10 systematic reviews, using true recall @ 95% there was a median reduction in screening burden of 47.1% (IQR: 37.5 to 58.0%). A median of 41.2% (IQR: 33.4 to 46.9%) of the excluded records needed to be screened to achieve true recall @ 95%. The median title/abstract screening hours saved using a modified screening approach at a true recall @ 95% was 29.8 h (IQR: 28.1 to 74.7 h). This was increased to a median of 36 h (IQR: 32.2 to 79.7 h) when considering the time saved not retrieving and screening full texts of the remaining 5% of records not yet identified as included at title/abstract. Among the 100 simulations (10 simulations per review), none of these 5% of records were a final included study in the systematic review. The reduction in screening burden to achieve true recall @ 95% compared to @ 100% resulted in a reduced screening burden median of 40.6% (IQR: 38.3 to 54.2%). CONCLUSIONS: The prioritization tool in DistillerSR can reduce screening burden. A modified or stop screening approach once a true recall @ 95% is achieved appears to be a valid method for rapid reviews, and perhaps systematic reviews. This needs to be further evaluated in prospective reviews using the estimated recall.

Evaporation and Electrowetting of Sessile Droplets on Slippery Liquid-Like Surfaces and Slippery Liquid-Infused Porous Surfaces (SLIPS).

Sessile droplet evaporation underpins a wide range of applications from inkjet printing to coating. However, drying times can be variable and contact-line pinning often leads to undesirable effects, such as ring stain formation. Here, we show voltage programmable control of contact angles during evaporation on two pinning-free surfaces. We use an electrowetting-on-dielectric approach and Slippery Liquid-Infused Porous (SLIP) and Slippery Omniphobic Covalently Attached Liquid-Like (SOCAL) surfaces to achieve a constant contact angle mode of evaporation. We report evaporation sequences and droplet lifetimes across a broad range of contact angles from 105°-67°. The values of the contact angles during evaporation are consistent with expectations from electrowetting and the Young-Lippman equation. The droplet contact areas reduce linearly in time, and this provides estimates of diffusion coefficients close to the expected literature value. We further find that the total time of evaporation over the broad contact angle range studied is only weakly dependent on the value of the contact angle. We conclude that on these types of slippery surfaces, droplet lifetimes can be predicted and controlled by the droplet's volume and physical properties (density, diffusion coefficient, and vapor concentration difference to the vapor phase) largely independent of the precise value of contact angle. These results are relevant to applications, such as printing, spraying, coating, and other processes, where controlling droplet evaporation and drying is important.

trips4health: Protocol of a single-blinded randomised controlled trial incentivising adults to use public transport for physical activity gain.

BACKGROUND: Public transport (PT) users typically accumulate more physical activity (PA) than private motor vehicle users yet redressing physical inactivity through transport-related PA (TRPA) interventions has received limited attention. Further, incentive-based strategies can increase leisure-time PA but their impact on TRPA, is unclear. This study's objective is to determine the impact of an incentive-based strategy on TRPA in a regional Australian setting. METHODS: trips4health is a single-blinded randomised controlled trial with a four-month intervention phase and subsequent six-month maintenance phase. Participants will be randomised to: an incentives-based intervention (bus trip credit for reaching bus trip targets, weekly text messages to support greater bus use, written PA guidelines); or an active control (written PA guidelines only). Three hundred and fifty adults (≥18 years) from southern Tasmania will be recruited through convenience methods, provide informed consent and baseline information, then be randomised. The primary outcome is change in accelerometer measured average daily step count at baseline and four- and ten-months later. Secondary outcomes are changes in: measured and self-reported travel behaviour (e.g. PT use), PA, sedentary behaviour; self-reported and measured (blood pressure, waist circumference, height, weight) health; travel behaviour perspectives (e.g. enablers/barriers); quality of life; and transport-related costs. Linear mixed model regression will determine group differences. Participant and PT provider level process evaluations will be conducted and intervention costs to the provider determined. DISCUSSION: trips4health will determine the effectiveness of an incentive-based strategy to increase TRPA by targeting PT use. The findings will enable evidence-informed decisions about the worthwhileness of such strategies. TRIAL REGISTRATION: ACTRN12619001136190. UNIVERSAL TRIAL NUMBER: U1111-1233-8050.

A new mechanism of strain transfer in polycrystals.

At the grain boundaries of plastically deforming polycrystals, strain transfer mechanisms can accommodate the shear strain carried by slip bands and mechanical twins to prevent stress build-ups and damage. So far, only the accommodation obtained through slip (and twinning) alone has been considered in the mechanism known as slip (and twin) transfer. Here, a strain transfer mechanism that also requires the rotation of the crystal lattice is demonstrated. A region of accumulated slip develops perpendicular to the active slip plane in the impinged grain. The slip gradients enable a localized lattice rotation that accommodates the shear strain in the incoming band, preventing the build-up of interfacial stresses. The mechanism operates preferentially at the boundaries between highly misoriented grains. Facilitating strain transfer at these interfaces opens up new possibilities to improve the mechanical properties of polycrystals, as discussed.

Improved diagnostic criteria for digital flexor tendon sheath pathology using contrast tenography.

BACKGROUND: Pathology of the digital flexor tendon sheath is a significant cause of lameness in the horse. Imaging is important to identify lesions and inform on prognosis prior to tenoscopic surgery. OBJECTIVES: To use a large population to evaluate 1) the sensitivity and specificity of digital flexor tendon sheath (DFTS) contrast radiographs in diagnosing manica flexoria (MF) tears, deep digital flexor tendon (DDFT) tears and constriction of the palmar/plantar annular ligament (PAL) using novel criteria; 2) predisposition to pathology in signalment and limb affected. STUDY DESIGN: Multicentre retrospective cohort study. METHODS: The medical records of 206 horses with lameness localised to the DFTS, contrast radiographs and subsequent tenoscopic surgery were reviewed. Breed and limb predispositions were evaluated for pathology of the DDFT, MF and PAL constriction. Contrast radiographs of the DFTS were reviewed by four masked operators and for each pathology the sensitivity, specificity and interobserver variability were calculated. RESULTS: Contrast tenography was a sensitive test for MF tears (92% confidence interval [CI] 88.4-94.4%; specificity 56%, CI 51.1-61.1%) and specific for diagnosing DDFT tears (73%, CI 68.6-76.8%; sensitivity 54%, CI 47.8-60.2%) but had a lower sensitivity (71%, CI 65.1-75.9% ) and specificity (45%, CI 39.1-52.0%) for PAL constriction. It had good to substantial interobserver agreement for MF and DDFT tears (Krippendorff's alpha 0.68 and 0.46 respectively). Ponies (57%) and cobs (58%) were significantly more likely to be affected with MF tears (other breeds 20-39%, P = 0.003) and Thoroughbreds (50%), warmbloods (45%) and draught breeds (48%) were more likely to have DDFT tears (other breeds 22-34%, P = 0.01). MF tears and PAL constriction were overrepresented in the hindlimbs compared to DDFT tears in forelimbs. MAIN LIMITATIONS: No standardisation of contrast radiographs was possible. The subjectivity of diagnosis of PAL constriction may also have led to bias. Radiographs were read as JPEGS reducing ability to manipulate images. CONCLUSIONS: Contrast radiography of the DFTS is accurate in the pre-operative diagnosis of DFTS pathologies. Different pathologies are overrepresented in certain breeds and limbs.

Physical activity and time budgets of Hadza forager children: Implications for self-provisioning and the ontogeny of the sexual division of labor.

OBJECTIVES: To determine the effects of age and sex on physical activity and time budgets of Hadza children and juveniles, 5-14 years old, including both in-camp and out-of-camp activities. METHODS: Behavioral data were derived from ~15 000 hourly in-camp scan observations of 76 individuals and 13 out-of-camp focal follows on nine individuals. The data were used to estimate energy expended and percentage of time engaged in a variety of routine activities, including food collection, childcare, making and repairing tools, and household maintenance. RESULTS: Our results suggest that (1) older children spend more time in economic activities; (2) females spend more time engaged in work-related and economic activities in camp, whereas males spend more time engaged in economic activities out of camp; and (3) foraging by both sexes tends to net caloric gains despite being energetically costly. CONCLUSIONS: These results show that, among the Hadza, a sexual division of labor begins to emerge in middle childhood and is well in place by adolescence. Furthermore, foraging tends to provide net caloric gains, suggesting that children are capable of reducing at least some of the energetic burden they place upon their parents or alloparents. The findings are relevant to our understanding of the ways in which young foragers allocate their time, the development of sex-specific behavior patterns, and the capacity of children's work efforts to offset the cost of their own care in a cooperative breeding environment.

Association between alcohol screening and brief intervention during routine check-ups and alcohol consumption among adults living in California.

BACKGROUND: Alcohol consumption accounts for 1 in 10 deaths among U.S. adults and cost upwards of $200 billion each year due to productivity loss. Alcohol Screening and Brief Intervention and Referral to Treatment (aSBIRT) was developed as a treatment approach for use in primary care to identify and reduce substance abuse. Although aSBIRT has proven to be successful, implementation rates remain low. METHODS: Using population level representative data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) conducted in California, this study utilizes logistic regression to analyze the association between self-reported drinking levels and screening and brief intervention practices during routine check-ups. RESULTS: The results demonstrated that the more an individual drank, the lower the odds of receiving aSBIRT during a routine check-up. Men had reduced odds of receiving intervention compared to women (odds ratio [OR], 2.21; confidence interval [CI], 1.68-2.90, p < 0.01) and diabetics had reduced odds of receiving intervention compared to non-diabetics (OR, 0.66; CI, 0.45-0.97, p = 0.3). Finally, those with lower income had reduced odds of intervention compared to those with higher income (OR, 1.84; CI, 1.33-2.56, p < 0.01). Among those who were at risk for alcohol abuse (83%) the intervention was only administered to 39%, and men had reduced odds of receiving intervention. CONCLUSION: Physicians perform alcohol screenings, but do not follow up the screening with intervention. Attention should be focused on delivering intervention to those identified as at risk for alcohol abuse through standard screening tools, specifically to men, diabetics, and lower income groups. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework.

BACKGROUND: Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. METHODS: An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. RESULTS: A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. CONCLUSION: The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity.

Magnetic resonance imaging reveals elevated aortic pulse wave velocity in obese and overweight adolescents.

The aortic pulse wave velocity (PWV) measured via cardiac magnetic resonance (CMR) can be used to non-invasively assess changes in arterial stiffness and potential underlying vascular dysfunction. This technique could unmask early arterial dysfunction in overweight and obese youth at risk for cardiovascular disease. We sought to determine the association between vascular stiffness, percentage body fat, body mass index (BMI), and cardiac function in adolescents across the weight spectrum through both CMR and standard applanation tonometry (AT)-based PWV measurements. PWV and left-ventricular cardiac function were assessed using 3.0 T CMR in obese and overweight (OB/OW) participants (n = 12) and controls (n = 7). PWV was also estimated via carotid-femoral AT. OB/OW participants did not differ from healthy-weight controls regarding cardiometabolic risk factors or physical activity levels, but there was a trend towards higher levels of triglycerides in obese/overweight participants (P = 0.07). Mean PWV was higher in obese participants when corrected for age and sex (P = 0.01), and was positively associated with BMI (ß = 0.51, P = 0.02). PWV estimated through AT was not significantly different between groups. Cardiac function measured by left-ventricular ejection fraction z-score was inversely associated with mean PWV (ß = -0.57, P = 0.026). Increasing arterial stiffness and decreasing cardiac function were evident among our overweight and obese cohort. PWV estimated by CMR could detect early increases in arterial stiffness vs. traditional AT measurements of PWV.

Rocuronium vs. succinylcholine for rapid sequence intubation: a Cochrane systematic review.

This systemic review was performed to determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during rapid sequence intubation of the trachea. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), MEDLINE (1966 to February Week 2 2015), and EMBASE (1988 to February 14 2015) for any randomised controlled trials or controlled clinical trials that reported intubating conditions comparing rocuronium and succinylcholine for rapid or modified rapid sequence intubation. The dose of rocuronium was at least 0.6 mg.kg-1 and succinylcholine was at least 1 mg.kg-1 . Sixty-six studies were identified and 50 included, representing 4151 participants. Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions (risk ratio (95%CI) 0.86 (0.81 to 0.92), n = 4151) and clinically acceptable intubation conditions (risk ratio (95%CI) 0.97 (0.95-0.99), n = 3992). A high incidence of detection bias amongst the trials coupled with significant heterogeneity means that the quality of evidence was moderate for these conclusions. Succinylcholine was more likely to produce excellent intubating conditions when using thiopental as the induction agent: risk ratio (95%CI) 0.81 (0.73-0.88), n = 2302) with or without the use of opioids (risk ratio (95%CI) 0.85 (0.78-0.93), n = 2292 or 0.85 (0.76-0.95), n = 1428).

Comparing the Resistance, Resilience, and Stability of Replicate Moving Bed Biofilm and Suspended Growth Combined Nitritation-Anammox Reactors.

Combined partial nitritation-anammox (PN/A) systems are increasingly being employed for sustainable removal of nitrogen from wastewater, but process instabilities present ongoing challenges for practitioners. The goal of this study was to elucidate differences in process stability between PN/A process variations employing two distinct aggregate types: biofilm [in moving bed biofilm reactors (MBBRs)] and suspended growth biomass. Triplicate reactors for each process variation were studied under baseline conditions and in response to a series of transient perturbations. MBBRs displayed elevated NH4+ removal rates relative to those of suspended growth counterparts over six months of unperturbed baseline operation but also exhibited significantly greater variability in performance. Transient perturbations led to strikingly divergent yet reproducible behavior in biofilm versus suspended growth systems. A temperature perturbation prompted a sharp reduction in NH4+ removal rates with no accumulation of NO2- and rapid recovery in MBBRs, compared to a similar reduction in NH4+ removal rates but a high level of accumulation of NO2- in suspended growth reactors. Pulse additions of a nitrification inhibitor (allylthiourea) prompted only moderate declines in performance in suspended growth reactors compared to sharp decreases in NH4+ removal rates in MBBRs. Quantitative fluorescence in situ hybridization demonstrated a significant enrichment of anammox in MBBRs compared to suspended growth reactors, and conversely a proportionally higher AOB abundance in suspended growth reactors. Overall, MBBRs displayed significantly increased susceptibility to transient perturbations employed in this study compared to that of suspended growth counterparts (stability parameter), including significantly longer recovery times (resilience). No significant difference in the maximal impact of perturbations (resistance) was apparent. Taken together, our results suggest that aggregate architecture (biofilm vs suspended growth) in PN/A processes exerts an unexpectedly strong influence on process stability.

A new survey to evaluate conflict of interest policies at academic medical centers.

BACKGROUND: A majority of academic medical centers (AMCs) have now adopted conflict of interest policies (COI) to address relationships with pharmaceutical and device industries that can increase the risk of bias in patient care, education and research. However, AMCs may have little information on the impact of their policies. This paper provides a new method, which is a free, publicly-available survey, to fill this information gap and improve COI programs at AMCs. METHODS & FINDINGS: The survey, piloted in three AMCs and designed in collaboration with national conflicts of interest policy experts, covers a range of universal compliance-related concerns, which allows institutions to tailor questions to align with their own policies and culture. The survey was low-burden, and provided important data for these AMCs to evaluate their policies. A descriptive analysis of the pooled pilot site data (n = 1578) was performed, which found that a majority of respondents did not have financial ties with industry and a majority was satisfied with specific COI policies at their institutions. The analysis also showed that the survey is sensitive to differences that AMCs will find meaningful. For instance, individuals with industry ties were significantly more likely than individuals without ties to think that COI policies unnecessarily hindered interactions with industry (p = .004), were ineffective at reducing harm to patients (p < .001), and were ineffective in reducing bias in medical education (p>.001). CONCLUSION: The survey is now free and publicly available for use by any institution. AMCs can use the results to update and refine policies, and to provide ongoing education regarding existing policies.

Does salmon calcitonin cause cancer? A review and meta-analysis.

Recently an association between the use of calcitonin and cancer has been postulated. We reviewed the biological rationale and performed an additional analysis of historical data with respect to the possibility. An association cannot be excluded, but the relationship is weak and causality is unlikely. The purpose of the present study is to review the strength of association and likelihood of a causal relationship between use of calcitonin and cancer. We reviewed the evidence for this association, including the molecular signaling mechanisms of calcitonin, preclinical data, an "experiment of nature," and the results of a previous meta-analysis which showed a weak association. We performed an additional meta-analysis to incorporate the data from a novel investigational oral formulation of salmon calcitonin. Review of the literature did not identify a cellular signaling mechanism of action which might account for a causal relationship or toxicologic or postmarketing data to support the thesis. Additional clinical results incorporated into previous meta-analyses weakened but did not completely negate the possibility of association. A causal association between calcitonin use and malignancy is unlikely, as there is little biological plausibility. The preponderance of nonclinical and clinical evidence also does not favor a causal relationship.

A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study.

Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with clopidogrel is associated with increased ischemic complications after percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic strategy among patients undergoing PCI for ST-elevation myocardial infarction (STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to a strategy of prasugrel 10 mg daily or an augmented dosing strategy of clopidogrel (150 mg daily for 6 days then 75 mg daily). The primary end point was the proportion of at-risk carriers exhibiting high on-treatment platelet reactivity (HPR), a marker associated with increased adverse cardiovascular events, after 1 month. Fifty-nine subjects (57.8%) were identified as carriers of at least one at-risk variant. Treatment with prasugrel significantly reduced HPR compared with clopidogrel by P2Y12 reaction unit (PRU) thresholds of >234 (0 vs 24.1%, P=0.0046) and PRU>208 (3.3 vs 34.5%, P=0.0025). The sensitivity of point-of-care testing was 100% (95% CI 88.0-100), 100% (86.3-100) and 96.9% (82.0-99.8) and specificity was 97.0% (88.5-99.5), 97.1% (89.0-99.5) and 98.5% (90.9-99.9) for identifying CYP2C19*2, ABCB1 TT and CYP2C19*17, respectively. Logistic regression confirmed carriers as a strong predictor of HPR (OR=6.58, 95% CI 1.24-34.92; P=0.03). We confirmed that concurrent identification of three separate genetic variants in patients with STEMI receiving PCI is feasible at the bedside. Among carriers of at-risk genotypes, treatment with prasugrel was superior to an augmented dosing strategy of clopidogrel in reducing HPR.

Protocol for the development of a CONSORT-equity guideline to improve reporting of health equity in randomized trials.

BACKGROUND: Health equity concerns the absence of avoidable and unfair differences in health. Randomized controlled trials (RCTs) can provide evidence about the impact of an intervention on health equity for specific disadvantaged populations or in general populations; this is important for equity-focused decision-making. Previous work has identified a lack of adequate reporting guidelines for assessing health equity in RCTs. The objective of this study is to develop guidelines to improve the reporting of health equity considerations in RCTs, as an extension of the Consolidated Standards of Reporting Trials (CONSORT). METHODS/DESIGN: A six-phase study using integrated knowledge translation governed by a study executive and advisory board will assemble empirical evidence to inform the CONSORT-equity extension. To create the guideline, the following steps are proposed: (1) develop a conceptual framework for identifying "equity-relevant trials," (2) assess empirical evidence regarding reporting of equity-relevant trials, (3) consult with global methods and content experts on how to improve reporting of health equity in RCTs, (4) collect broad feedback and prioritize items needed to improve reporting of health equity in RCTs, (5) establish consensus on the CONSORT-equity extension: the guideline for equity-relevant trials, and (6) broadly disseminate and implement the CONSORT-equity extension. DISCUSSION: This work will be relevant to a broad range of RCTs addressing questions of effectiveness for strategies to improve practice and policy in the areas of social determinants of health, clinical care, health systems, public health, and international development, where health and/or access to health care is a primary outcome. The outcomes include a reporting guideline (CONSORT-equity extension) for equity-relevant RCTs and a knowledge translation strategy to broadly encourage its uptake and use by journal editors, authors, and funding agencies.

Effects of aerobic and resistance training on abdominal fat, apolipoproteins and high-sensitivity C-reactive protein in adolescents with obesity: the HEARTY randomized clinical trial.

OBJECTIVES: To investigate the effects of aerobic training, resistance training, or both on abdominal subcutaneous fat (subcutaneous adipose tissue (SAT)) (deep and superficial), visceral fat (visceral adipose tissue (VAT)), apolipoproteins A-1 and B (ApoA-1, ApoB), ApoB/ApoA-1 ratio and high-sensitivity C-reactive protein (HSCRP) in post-pubertal adolescents with obesity. PARTICIPANTS: After a 4-week supervised moderate-intensity exercise run-in period, 304 postpubertal adolescents with overweight (body mass index (BMI) ⩾85th percentile for age and sex+diabetes risk factor) or obesity (⩾95th BMI percentile) aged 14-18 years were randomized to four groups for 22 weeks (5 months): aerobic training, resistance training, combined training or a non-exercising control. METHODS: This study used a randomized controlled design. All groups received dietary counseling designed to promote healthy eating with a maximum daily energy deficit of 250 kcal. Abdominal fat (SAT and VAT) at the level of the fourth and fifth lumbar vertebrae (L4-L5) was measured by magnetic resonance imaging and ApoA-1, ApoB and HSCRP were measured after a 12-h fast at baseline and after 6 months. RESULTS: Changes in SAT at L4-L5 were -16.2 cm(2) in aerobic (P=0.04 vs control), -22.7 cm(2) in resistance (P=0.009 vs control) and -18.7 cm(2) in combined (P=0.02 vs control). Combined training reduced ApoB levels from 0.81±0.02 to 0.78±0.02 g l(-1) (P=0.04 vs control) and ApoB/ApoA-1 ratio from 0.67±0.02 to 0.64±0.02 (P=0.02 vs control and P=0.04 vs aerobic). There were no significant differences in VAT, ApoA-1 or HSCRP levels between groups. CONCLUSIONS: Aerobic and resistance training and their combination decreased abdominal SAT in adolescents with obesity. Combined training caused greater improvements in ApoB/ApoA-1 ratio compared with aerobic training alone.

Impact of coexistence of flocs and biofilm on performance of combined nitritation-anammox granular sludge reactors.

Nitrogen (N) removal from high-strength wastewater can be accomplished in single-stage combined nitritation-anammox reactors with suspended growth biomass composed of floccular sludge, granular sludge, or of any mix of these 2 different sludge fractions. To date, the influence of floccular biomass on granular sludge reactor performance and stability has not been investigated experimentally or numerically. To address this knowledge gap, two 1D multi-species models were developed in Aquasim to assess the importance of small levels of flocs in putatively granular sludge combined nitritation-anammox reactors for different bulk oxygen concentrations and organics loads. The models included the growth and decay of aerobic ammonium-oxidizing organism (AOO), nitrite-oxidizing organisms (NOO), heterotrophic organisms (OHO), and anammox organisms (AMO) in exclusively granular sludge reactors, and in granular sludge reactors with small levels (∼5% of total biomass) of flocs. While maximum N removal efficiencies were similar for both model structures, floc addition led to a lower optimal dissolved oxygen concentration (DO) as well as a narrower maximum N removal peak, suggesting that small levels of floccular material may decrease process robustness to bulk oxygen changes. For some DO levels, this led to drastic efficiency drops. Furthermore, floc addition also led to substantial segregation in activity and microbial population distribution, with AOO, NOO and OHO concentrated in flocs and AMO concentrated in granules. Increased organic loading (COD:N = 4:3) improved maximum N removal efficiency in both model structures, but yielded substantially different predictions for optimal DO setpoint and process robustness to variations in DO. Taken together, our results indicate that even small levels of floccular biomass in biofilm reactors can have profound implications for reactor performance and optimization and for segregation of linked microbial processes, and suggest that the common practice of neglecting small levels of floccular material in biofilm models and in practice may lead to erroneous predictions.

Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced, inflammatory, or early HER2-positive breast cancer in Canada.

OBJECTIVE: The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC. METHODS: A cost-utility analysis (CUA) was conducted using a three health state Markov model ('event-free', 'relapsed', and 'dead'). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored. RESULTS: Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230-$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA). CONCLUSION: Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.