Prehospital identification of intracerebral haemorrhage: a scoping review of early clinical features and portable devices.

INTRODUCTION: Prehospital identification of intracerebral haemorrhage (ICH) in suspected stroke cases may enable the initiation of appropriate treatments and facilitate better-informed transport decisions. This scoping review aims to examine the literature to identify early clinical features and portable devices for the detection of ICH in the prehospital setting. METHODS: Three databases were searched via Ovid (MEDLINE, EMBASE and CENTRAL) from inception to August 2022 using prespecified search strategies. One reviewer screened all titles, abstracts and full-text articles for eligibility, while a second reviewer independently screened 20% of the literature during each screening stage. Data extracted were tabulated to summarise the key findings. RESULTS: A total of 6803 articles were screened for eligibility, of which 22 studies were included for analysis. Among them, 15 studies reported on early clinical features, while 7 considered portable devices. Associations between age, sex and comorbidities with the presence of ICH varied across studies. However, most studies reported that patients with ICH exhibited more severe neurological deficits (n=6) and higher blood pressure levels (n=11) at onset compared with other stroke and non-stroke diagnoses. Four technologies were identified for ICH detection: microwave imaging technology, volumetric impedance phase shift spectroscopy, transcranial ultrasound and electroencephalography. Microwave and ultrasound imaging techniques showed promise in distinguishing ICH from other diagnoses. CONCLUSION: This scoping review has identified potential clinical features for the identification of ICH in suspected stroke patients. However, the considerable heterogeneity among the included studies precludes meta-analysis of available data. Moreover, we have explored portable devices to enhance ICH identification. While these devices have shown promise in detecting ICH, further technological development is required to distinguish between stroke subtypes (ICH vs ischaemic stroke) and non-stroke diagnoses.

Integrating health, nutrition, and environmental impacts of foods: a life cycle impact assessment and modelling analysis of foods in Canada.

BACKGROUND: Given the urgency of transitioning towards sustainable nutrition, dietary shifts that provide co-benefits to human health and the environment are imperative. There is currently no database of the environmental impacts of foods that reflects Canada's unique geographical and agri-climatic context and regional inputs and emissions. To determine sustainable diets, harmonising nutritional considerations with environmental impacts is also essential for an equitable comparison of foods. We aimed to develop a Canadian Food Life Cycle Inventory database and a multidimensional index to enable a joint assessment of the health and environmental impacts of foods in Canada. METHODS: The Canadian Food Life Cycle Inventory database uses life cycle assessment methodology to evaluate environmental impacts. The datasets mirror Canada's food consumption patterns, averaging the spectrum of agricultural practices weighted by domestic production and import shares. The database is structured according to the nomenclature and categorisation of the Canadian Nutrient File. Environmental sustainability is assessed using a cradle-to-grave approach, including indicators such as greenhouse gas emissions, eutrophication, particulate matter, freshwater usage, land use, non-renewable energy consumption, and food loss and waste. Environmental impacts are quantified through an environmental impact score (EIS) assigned to each impact category for a given food. The EIS-nutrition (EIS-N) integrates the evaluation of nutritional quality with environmental impacts using Nutri-Score, a validated food nutrient-profiling tool. The EIS-N is modelled as a ratio of the EIS to the Nutri-Score values. FINDINGS: Preliminary results show the greatest environmental impacts for animal-based foods, particularly beef, in agreement with current literature. Foods with greater nutritional quality also generally show greater environmental sustainability, with some exceptions for particular impact categories. INTERPRETATION: The database and index have potential to serve as powerful tools to support researchers, policy makers, and consumers, harnessing big data to drive efficient food and climate solutions for systems transformation. FUNDING: Province of Ontario and University of Toronto, CIHR SMART Healthy Cities Training Platform, and University of Toronto's Temerty Faculty of Medicine.

Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment.

PURPOSE: Novel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but toxicities limit widespread use. The selective Bruton tyrosine kinase (BTK) inhibitor acalabrutinib has activity in patients with R/R DLBCL but durable responses are uncommon. STAT3 inhibition has demonstrated clinical activity in DLBCL. PATIENTS AND METHODS: Final results of the phase I study of acalabrutinib plus STAT3 inhibitor (danvatirsen; AZD9150) in patients with R/R DLBCL are reported. Danvatirsen 200 mg intravenous infusion [Days 1, 3, 5 (Cycle 1); weekly infusions starting Day 8, Cycle 1] was administered in combination with oral acalabrutinib 100 mg twice daily until progressive disease (PD) or unacceptable toxicity. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy, pharmacokinetics, and immunogenicity. RESULTS: Seventeen patients received combination treatment. One dose-limiting toxicity (Grade 3 liver transaminase) occurred in 1 patient. The most common reason for treatment discontinuation was PD (65%). In evaluable patients (n = 17), objective response rate was 24%; median duration of response was 1.9 months. All responders with available DLBCL cell-of-origin data were either activated B-cell or nongerminal center B-cell like subtype. Genetic subtype did not correlate with response. Baseline and longitudinal plasma cell-free DNA (cfDNA) concentrations were mostly higher in nonresponding patients. cfDNA changes were generally concordant with imaging. Pretreatment circulating B-cell levels were higher in responders versus nonresponders. CONCLUSIONS: Targeting both STAT3 and BTK in combination is safe and tolerable but efficacy is limited in R/R DLBCL. Results support evaluation of circulating tumor DNA as a biomarker for clinical response.

Detecting falsified oral contraceptives by visual assessment and diffuse reflectance spectroscopy (350-2500 nm): the need for supplementing traditional pharmacopeia techniques and the public health implications.

Objectives: Substandard and falsified pharmaceuticals can present a major health risk, particularly for low- and middle-income countries. In a Sub-Saharan African market, United States Agency for International Development (USAID) staff found an oral contraceptive product (0.15 mg levonorgestrel/0.03 mg ethinyl estradiol) labeled with a logo (and brand name) visually matching one historically used by USAID but purportedly manufactured by an unauthorized source. Additional assessment was conducted to determine if more evidence of falsification was present to better understand the public health impact. Study design: Relative to a control, the suspect sample was assessed visually for tablet features and with United States and International Pharmacopeia methods for levonorgestrel/ethinyl estradiol tablets. Diffuse reflectance spectra (350-2500 nm) were collected to further characterize the sample. Results: Although the suspect sample aligned with pharmacopeia tests, visual examination of tablet characteristics and diffuse reflectance spectroscopy (350-2500 nm) assessments supported the tablets were not the same as control samples, confirming the suspect sample was falsified. These results raised concerns for the overall regulatory oversight available for the market with uncertainty regarding the true clinical bioequivalence levels (although adequate dissolution levels were observed). Conclusions: Comprehensive characterization of suspect pharmaceuticals from the field can often be required depending on the nature of the sample and can have dramatic implications for understanding the public health risks to the end user within the local market. Simple visual assessment and spectroscopic techniques to screen a sample can help to supplement traditional pharmacopeia approaches. Implications: Proper characterization of suspect pharmaceuticals is necessary to best understand their potential public health impact. Situations can occur where traditional pharmacopeial techniques may not adequately characterize a sample. Visual assessments and diffuse reflectance spectroscopy can be supplemented to provide a more holistic analysis.

Mean kinetic temperature evaluations through simulated temperature excursions and risk assessment with oral dosage usage for health programs.

BACKGROUND: Temperature excursions occur during the transport and storage of pharmaceuticals, and often result in considerable losses for public health programs operating in countries with limited resources. After a temperature excursion has been identified, often products are discarded without any additional risk assessments. Consulting the manufacturer is the preferred approach but can be challenging depending on the responsiveness of the manufacturer. However, decisions are often required quickly depending on program needs and available stock in country. METHODS: To provide further guidance, simulations have been conducted based on mean kinetic temperature evaluations using accepted default kinetic parameters to assess loss of shelf-life for scenarios involving various levels of temperature excursions on a model pharmaceutical at different recommended storage conditions, shelf-life, and long-term storage conditions. RESULTS: Although an immediate loss to shelf-life occurred with excursions when the product was stored at the maximum allowed temperature, more extended excursion could be withstood before loss of shelf-life was detected when long-term storage was maintained at temperatures below the maximum storage condition for the product. With the assumption that a shelf-life loss of 2 weeks was negligible when managing program stock, a risk assessment was conducted to outline the various times that excursions at different temperatures could be considered low risk to the program. CONCLUSIONS: Depending on the level of the temperature excursion and the guidance provided by the manufacturer, public health programs will have further information with this assessment to guide decisions that impact safety to the end user and resource management due to temperature excursions that can occur.

Serial right heart catheter assessment between balloon pulmonary angioplasty sessions identify procedural factors that influence response to treatment.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome. METHODS: Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response. RESULTS: Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson's r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate. CONCLUSIONS: The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA.

A low-cost and portable near-infrared spectrometer using open-source multivariate data analysis software for rapid discriminatory quality assessment of medroxyprogesterone acetate injectables.

Medroxyprogesterone acetate (MPA) injectable suspensions are used by millions of women for family planning and hormonal therapy. Falsified or substandard medications may result in a health risk for consumers. Near-infrared spectroscopy (NIR) has previously been applied as a means of non-destructive and rapid screening of product quality compliance. These methods offer advantages but can be logistically and cost prohibitive for field use in resource limited areas. Here, a handheld spectrometer (900-1700 nm) with open-sourced software is used to evaluate vials of MPA from three suppliers (N = 227 vials) and verified by a benchtop UV-VIS-NIR (350-2500 nm) with licensed software. Multivariate data analysis assesses the spectral signatures of samples and builds a discriminant classification method based on Mahalanobis distances calculated from a principal component analysis scores. The handheld device paired with open-source software resulted in a product discrimination accuracy of 100% (verified by benchtop UV-VIS-NIR and chemical testing data) as well indicating that the low-cost field portable device is suitable for rapidly assessing samples in resource limited areas for consistency of manufacturing and sourcing.

Regional extracorporeal membrane oxygenation retrieval service during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic: an interdisciplinary team approach to maintain service provision despite increased demand.

OBJECTIVES: Coronavirus disease 2019 is a new contagious disease that has spread rapidly across the world. It is associated with high mortality in those who develop respiratory complications and require admission to intensive care. Extracorporeal membrane oxygenation (ECMO) is a supportive therapy option for selected severely ill patients who deteriorate despite the best supportive care. During the coronavirus disease 2019 pandemic, extra demand led to staff reorganization; hence, cardiac surgery consultants joined the ECMO retrieval team. This article describes how we increased service provisions to adapt to the changes in activity and staffing. METHODS: The data were collected from 16 March 2020 to 8 May 2020. The patients were referred through a dedicated Web-based referral portal to cope with increasing demand. The retrieval team attended the referring hospital, reviewed the patients and made the final decision to proceed with ECMO. RESULTS: We reported 41 ECMO retrieval runs during this study period. Apart from staffing changes, other retrieval protocols were maintained. The preferred cannulation method for veno-venous ECMO was drainage via the femoral vein and return to the right internal jugular vein. There were no complications reported during cannulation or transport. CONCLUSIONS: Staff reorganization in a crisis is of paramount importance. For those with precise transferrable skills, experience can be gained quickly with appropriate supervision. Therefore, the team members were selected based on skill mix rather than on roles that are more traditional. We have demonstrated that an ECMO retrieval service can be reorganized swiftly and successfully to cope with the sudden increase in demand by spending cardiac surgeons services to supplement the anaesthetic-intensivist roles.

Triage of patients with venous and lymphatic diseases during the COVID-19 pandemic - The Venous and Lymphatic Triage and Acuity Scale (VELTAS) : A consensus document of the International Union of Phlebology (UIP), Australasian College of Phlebology (ACP), American Vein and Lymphatic Society (AVLS), American Venous Forum (AVF), European College of Phlebology (ECoP), European Venous Forum (EVF), Interventional Radiology Society of Australasia (IRSA), Latin American Venous Forum, Pan-American Society of Phlebology and Lymphology and the Venous Association of India (VAI) This consensus document has been co-published in Phlebology [DOI: 10.1177/0268355520930884] and Journal of Vascular Surgery: Venous and Lymphatic Disorders [DOI: 10.1016/j.jvsv.2020.05.002]. The publications are identical except for minor stylistic and spelling differences in keeping with each journal's style. The contribution has been published under a Attribution-Non Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0), (https://creativecommons.org/licenses/by-nc-nd/4.0/).

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.

A solution to minimum sample size for regressions.

Regressions and meta-regressions are widely used to estimate patterns and effect sizes in various disciplines. However, many biological and medical analyses use relatively low sample size (N), contributing to concerns on reproducibility. What is the minimum N to identify the most plausible data pattern using regressions? Statistical power analysis is often used to answer that question, but it has its own problems and logically should follow model selection to first identify the most plausible model. Here we make null, simple linear and quadratic data with different variances and effect sizes. We then sample and use information theoretic model selection to evaluate minimum N for regression models. We also evaluate the use of coefficient of determination (R2) for this purpose; it is widely used but not recommended. With very low variance, both false positives and false negatives occurred at N < 8, but data shape was always clearly identified at N ≥ 8. With high variance, accurate inference was stable at N ≥ 25. Those outcomes were consistent at different effect sizes. Akaike Information Criterion weights (AICc wi) were essential to clearly identify patterns (e.g., simple linear vs. null); R2 or adjusted R2 values were not useful. We conclude that a minimum N = 8 is informative given very little variance, but minimum N ≥ 25 is required for more variance. Alternative models are better compared using information theory indices such as AIC but not R2 or adjusted R2. Insufficient N and R2-based model selection apparently contribute to confusion and low reproducibility in various disciplines. To avoid those problems, we recommend that research based on regressions or meta-regressions use N ≥ 25.

Assessment of the direct economic losses associated with hydatid disease (Echinococcus granulosus sensu stricto) in beef cattle slaughtered at an Australian abattoir.

Bovine hydatid disease, characterised by fluid-filled hydatid cysts, is regularly found in the offal of beef cattle at slaughter. Organs found to be infected at slaughter are removed to preclude them from entering the human food chain. The organs are either downgraded to pet food or condemned. Previous studies have focussed on total economic losses, but have not calculated the cost of disease per animal, which would be useful information for producers when determining how best to manage hydatid disease. This study estimated the direct losses associated with hydatid disease in beef cattle slaughtered at an Australian beef abattoir both at the population (all cattle slaughtered) and individual animal level. Data on annual prevalence of hydatid disease in beef cattle were obtained from an Australian abattoir for the years 2011-2017. The direct losses resulting from the condemnation and downgrading of offal infected with hydatid cysts at the abattoir were estimated using data stratified by age, sex and feed-type. Official and literature-based sources of organ weight and price were used to estimate direct losses associated with hydatid disease in beef cattle slaughtered at the abattoir. Uncertainty and variability in input parameters were represented using uniform distributions and Monte Carlo sampling was used to model output parameter uncertainty. Out of 1,097,958 beef cattle slaughtered between January 2011 and December 2017, 97,832 (8.9%) were reported infected with hydatid disease. The median estimated direct loss to the abattoir for the duration of the study period was AU$655,560 (95% confidence interval [CI] AU$544,366-787,235). This equated to approximately AU$6.70 (95% CI AU$5.56-8.05) lost per infected animal. The annual median estimated direct losses due to hydatid disease at the abattoir were AU$93,651 (95% CI AU$77,767-112,462). Direct losses varied each year of the study and ranged from AU$38,683 in 2016 to AU$163,006 in 2014. This estimate of the direct losses associated with bovine hydatid disease most likely underestimates the true extent of the overall losses because indirect losses such as reduced carcass weights were not estimated in this study. Nevertheless, these estimates illustrate the negative economic impact of bovine hydatid disease and demonstrate that improved surveillance to enable control of hydatid disease should be considered both in Australia and globally. It would be worthwhile to estimate the losses in other beef abattoirs for the same time period to compare results, and to investigate the cost-benefit of control programs for bovine hydatid disease.

Lung procurement after circulatory death from donor supported on biventricular assist devices and functional assessment with portable normothermic ex vivo organ care system.

The criteria for donor organ acceptance are broadening. We describe a successful lung transplantation following donation after circulatory death of extended criteria donor supported with biventricular assist devices. During the redo sternotomy, we used the biventricular assist devices cannulae to perfuse the lungs through the pulmonary artery cannula and draining via the left and right ventricle cannula, significantly minimizing the ischaemic time. Following procurement, we utilized portable ex vivo lung system (Transmedics™ Lung OCS) to optimize, assess and eventually to proceed to a successful transplant.

Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: Assessment of Causal Relations.

While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.

Positioning the Value of Dietary Carbohydrate, Carbohydrate Quality, Glycemic Index, and GI Labelling to the Canadian Consumer for Improving Dietary Patterns.

The objectives of this qualitative study was to: (1) understand Canadian consumers' knowledge and perception of dietary carbohydrates, carbohydrate quality, and the glycemic index (GI); and (2) determine Canadian's receptiveness to GI labelling to assist with identifying and consuming foods of higher carbohydrate quality. Focus groups were recruited in Vancouver, Toronto, and Montreal and grouped according to body mass index (BMI) (NBW, normal body weight; PO, previously obese; and OW/OB, overweight/obese) and diagnosis with prediabetes and diabetes (PO (Vancouver) and OW/OB (Montreal and Toronto). Subjects in all groups linked excess consumption of carbohydrate with weight gain. PO and OW/OB groups were conflicted between perceived negative consequences and feelings of pleasure associated with carbohydrate consumption. Subjects were largely unfamiliar with the term 'carbohydrate quality', but were often associated with classifying carbohydrates as 'good' or 'bad'. The concept of the GI resonated well across groups after exposure to corresponding educational materials. However, NBW groups largely felt that the GI was irrelevant to their dietary choices as they did not have a history of diabetes. PO and OW/OB groups associated the GI with diabetes management. The concept of a GI labelling program to help facilitate healthier carbohydrate choices was well received across all groups, especially when the low GI was interpreted as giving permission to consume foods they enjoyed eating. Results suggest that the GI could be used as a consumer-facing labelling program in Canada and assist with de-stigmatizing carbohydrate foods by helping to facilitate the consumption of carbohydrate foods that align with healthy dietary patterns.

An Appetite for Modernizing the Regulatory Framework for Protein Content Claims in Canada.

The need for protein-rich plant-based foods continues as dietary guidelines emphasize their contribution to healthy dietary patterns that prevent chronic disease and promote environmental sustainability. However, the Canadian Food and Drug Regulations provide a regulatory framework that can prevent Canadian consumers from identifying protein-rich plant-based foods. In Canada, protein nutrient content claims are based on the protein efficiency ratio (PER) and protein rating method, which is based on a rat growth bioassay. PERs are not additive, and the protein rating of a food is underpinned by its Reasonable Daily Intake. The restrictive nature of Canada's requirements for supporting protein claims therefore presents challenges for Canadian consumers to adapt to a rapidly changing food environment. This commentary will present two options for modernizing the regulatory framework for protein content claims in Canada. The first and preferred option advocates that protein quality not be considered in the determination of the eligibility of a food for protein content claims. The second and less preferred option, an interim solution, is a framework for adopting the protein digestibility corrected amino acid score as the official method for supporting protein content and quality claims and harmonizes Canada's regulatory framework with that of the USA.

Velocity, Oxygen Uptake, and Metabolic Cost of Pull, Kick, and Whole-Body Swimming.

PURPOSE: The contributions of the limbs to velocity and metabolic parameters in front-crawl swimming at different intensities have not been identified considering both stroke and kick rate. Consequently, velocity, oxygen uptake (V̇O2), and metabolic cost of swimming with the whole body (swim), the upper limbs only (pull), and lower limbs only (kick) were compared with stroke and kick rate controlled. METHODS: Twenty elite swimmers completed six 200-m trials: 2 swim, 2 pull, and 2 kick. Swim trials were guided by underwater lights at paces equivalent to 65% ± 3% and 78% ± 3% of participants' 200-m-freestyle personal-best pace; paces were described as low and moderate, respectively. In the pull and kick trials, swimmers aimed to match the stroke and kick rates, respectively, recorded during the swim trials. V̇O2 was measured continuously, with velocity and metabolic cost calculated for each 200-m effort. RESULTS: The velocity contribution of the upper limbs (mean ± SD; low 63.9% ± 6.2%, moderate 59.6% ± 4.2%) was greater than that of the lower limbs to a large extent at both intensities (low ES = 4.40, moderate ES = 4.60). The V̇O2 used by the upper limbs differed between the intensities (low 55.5% ± 6.9%, moderate 51.4% ± 4.0%; ES = 0.74). The lower limbs were responsible for a greater percentage of the metabolic cost than the upper limbs at both intensities (low 56.1% ± 9.5%, ES = 1.30; moderate 55.1% ± 6.6%, ES = 1.55). CONCLUSIONS: Implementation of this testing protocol before and after a pull- or kick-training block will enable sport scientists to determine how the velocity contributions and/or metabolic cost of the upper- and lower-limb actions have responded to the training program.

Assessment of learning curves in complex surgical interventions: a consecutive case-series study.

BACKGROUND: Surgical interventions are complex, which complicates their rigorous assessment through randomised clinical trials. An important component of complexity relates to surgeon experience and the rate at which the required level of skill is achieved, known as the learning curve. There is considerable evidence that operator performance for surgical innovations will change with increasing experience. Such learning effects complicate evaluations; the start of the trial might be delayed, resulting in loss of surgeon equipoise or, if an assessment is undertaken before performance has stabilised, the true impact of the intervention may be distorted. METHODS: Formal estimation of learning parameters is necessary to characterise the learning curve, model its evolution and adjust for its presence during assessment. Current methods are either descriptive or model the learning curve through three main features: the initial skill level, the learning rate and the final skill level achieved. We introduce a fourth characterising feature, the duration of the learning period, which provides an estimate of the point at which learning has stabilised. We propose a two-phase model to estimate formally all four learning curve features. RESULTS: We demonstrate that the two-phase model can be used to estimate the end of the learning period by incorporating a parameter for estimating the duration of learning. This is achieved by breaking down the model into a phase describing the learning period and one describing cases after the final skill level is reached, with the break point representing the length of learning. We illustrate the method using cardiac surgery data. CONCLUSIONS: This modelling extension is useful as it provides a measure of the potential cost of learning an intervention and enables statisticians to accommodate cases undertaken during the learning phase and assess the intervention after the optimal skill level is reached. The limitations of the method and implications for the optimal timing of a definitive randomised controlled trial are also discussed.

Velocity, aerobic power and metabolic cost of whole body and arms only front crawl swimming at various stroke rates.

PURPOSE: Stroke rate (SR) has not been considered in previous research examining the relative roles of the limbs in front-crawl performance. This study compared velocity, aerobic power ([Formula: see text]) and metabolic cost (C) between whole body (WB) and arms only (AO) front-crawl swimming across various intensities while controlling SR. METHODS: Twenty Australian national swimmers performed six 200 m front-crawl efforts under two conditions: (1) WB swimming and, (2) AO swimming. Participants completed the 200 m trials under three SR conditions: "low" (22-26 stroke-cycles min(-1)), "moderate" (30-34 stroke-cycles min(-1) and "high" (38-42 stroke-cycles min(-1)). [Formula: see text] was continuously measured, with C, velocity, SR, and kick rate calculated for each effort. RESULTS: Regardless of the SR condition and sex, AO velocity was consistently lower than WB velocity by ~11.0 % (p < 0.01). AO [Formula: see text] was lower than WB [Formula: see text] at all SR conditions for females (p < 0.01) and at the "high" SR for males (p < 0.01). C did not differ between WB and AO at any SR for both sexes (p > 0.01). When C was expressed as a function of velocity, WB and AO regression equations differed for males (p = 0.01) but not for females (p = 0.087). Kick rate increased as SR increased (p < 0.01), though the kick-to-stroke rate ratio remained constant. CONCLUSION: Elite swimmers gain ~11 % in velocity from their kick and, when used in conjunction with the arm stroke at the swimmers' preferred frequency, the metabolic cost of WB and AO swimming is the same. Coaches should consider these results when prescribing AO sets if their intention is to reduce the metabolic load.

Operability assessment in CTEPH: Lessons from the CHEST-1 study.

Pulmonary endarterectomy is the gold standard treatment for chronic thromboembolic pulmonary hypertension and is potentially curative, although some patients are unsuitable for pulmonary endarterectomy and require alternative management. Lack of standardized assessment of pulmonary endarterectomy eligibility risks suboptimal treatment in some patients. We discuss the implications for future clinical trials and practice of a unique operability assessment in patients who have chronic thromboembolic pulmonary hypertension and were initially screened for inclusion in the CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase Stimulator Trial-1) study. The CHEST-1 study evaluated riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. Screened patients who were initially considered "inoperable" underwent central independent adjudication by a committee of experienced surgeons, or local adjudication in collaboration with an experienced surgeon. Operability decisions were based on accessibility of thrombi and the association between pulmonary vascular resistance (PVR) and the extent of obstruction, using pulmonary angiography/computed tomography with ventilation/perfusion scintigraphy as the minimum diagnostic tests. Of 446 patients screened for CHEST-1, a total of 188 and 124 underwent central and local adjudication, respectively, after being initially considered to be "inoperable." After a second assessment by an experienced surgeon, 69 of these 312 "inoperable" patients were deemed operable. Rigorous measures in CHEST-1 guaranteed that only technically inoperable patients, or patients who had persistent/recurrent pulmonary hypertension, were enrolled, thus ensuring that only patients for whom surgery was not an option were enrolled. This study design sets new standards for future clinical trials and practice in CTEPH, helping to ensure that patients who have CTEPH receive optimal treatment.