Efficacy and safety of the ustekinumab biosimilar ABP 654 in patients with moderate-to-severe plaque psoriasis: a randomized, double-blinded, active-controlled, comparative clinical study over 52 weeks.

BACKGROUND: ABP 654 is a biosimilar to ustekinumab reference product (RP). ABP 654 has been shown to have an amino acid sequence identical to ustekinumab RP and they are similar in structure, purity, and potency as well as clinical pharmacokinetics and safety in healthy volunteers. OBJECTIVES: This randomized, double-blinded, active-controlled, single-transition, comparative clinical study (ClinicalTrials.gov ID NCT04607980) was conducted to compare the efficacy, safety, and immunogenicity of ABP 654 and ustekinumab RP in patients with moderate-to-severe plaque psoriasis. METHODS: Patients were randomized in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a weight-based dose of 45 mg or 90 mg administered subcutaneously on day 1 (week 0), week 4, and week 16. At week 28, patients with a ≥75% improvement in Psoriasis Area and Severity Index (PASI) were re-randomized such that those initially randomized to ABP 654 continued to receive ABP 654 and those initially randomized to ustekinumab RP were re-randomized to either continue on ustekinumab RP or transition to ABP 654. The primary efficacy endpoint was PASI percent improvement from baseline to week 12. Secondary endpoints included additional efficacy measurements as well as an assessment of adverse events and antidrug antibodies. RESULTS: At week 12, the observed mean (SD) PASI percent improvement from baseline was 81.9 (19.9) and 81.9 (19.6) for the ABP 654 and ustekinumab RP treatment groups, respectively. The point estimate of the mean difference in PASI percent improvement from baseline to week 12 between the treatment groups was 0.14 with a 2-sided 90% confidence interval (CI) of (-2.6, 2.9), well within the prespecified similarity margin of (-10, +10). In addition, throughout the study, secondary efficacy analyses and safety and immunogenicity profiles were similar across the treatment groups. CONCLUSIONS: These results indicate that ABP 654 and ustekinumab RP are clinically similar in efficacy, safety, and immunogenicity in patients with moderate-to-severe plaque psoriasis. Further, a single transition from ustekinumab RP to ABP 654 at week 28 had no impact on the efficacy, safety, or immunogenicity results for the remainder of the 52-week study, supporting a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.

Primary care practitioner and patient perspectives on care following bariatric surgery: A meta-synthesis of qualitative research.

Primary care is central to ongoing health care following bariatric surgery and patients indicate a preference for receiving follow-up support by their primary care practitioner (PCP). This meta-synthesis investigates the perspectives of both PCPs and patients in post-bariatric surgery care provided by PCPs. The aim was to synthesize themes from qualitative research to recommend improvements in post-bariatric surgery clinical care in primary care settings. Systematic searches of Scopus, Medline, EMBASE, PsycINFO, the Cochrane Library, and Google Scholar resulted in the inclusion of eight papers in the meta-synthesis. Papers were critiqued using the Critical Appraisal Skills Program (CASP) and thematically coded in Quirkos Cloud. Seven themes were reached by author consensus including stigma and judgment; clinician barriers and facilitators; patient-related support needs; communication considerations; patient context or determinants; health care setting; and adapting to life after surgery. PCPs reported barriers including poor communication and guidance from bariatric surgery centers, limited knowledge and training in bariatric patient care, and patients who may have unrealistic outcomes and poor health literacy. Patients seek comprehensive care from their PCP, however, barriers hindering the provision of this care include adverse surgical outcomes, a poor relationship with their PCP, and limited and short-term follow-up care from the PCP. Insights from this meta-synthesis offer actionable recommendations for PCPs and bariatric surgery centers to enhance patient care immediately.

The importance of geography in forecasting future fire patterns under climate change.

An increasing amount of California's landscape has burned in wildfires in recent decades, in conjunction with increasing temperatures and vapor pressure deficit due to climate change. As the wildland-urban interface expands, more people are exposed to and harmed by these extensive wildfires, which are also eroding the resilience of terrestrial ecosystems. With future wildfire activity expected to increase, there is an urgent demand for solutions that sustain healthy ecosystems and wildfire-resilient human communities. Those who manage disaster response, landscapes, and biodiversity rely on mapped projections of how fire activity may respond to climate change and other human factors. California wildfire is complex, however, and climate-fire relationships vary across the state. Given known geographical variability in drivers of fire activity, we asked whether the geographical extent of fire models used to create these projections may alter the interpretation of predictions. We compared models of fire occurrence spanning the entire state of California to models developed for individual ecoregions and then projected end-of-century future fire patterns under climate change scenarios. We trained a Maximum Entropy model with fire records and hydroclimatological variables from recent decades (1981 to 2010) as well as topographic and human infrastructure predictors. Results showed substantial variation in predictors of fire probability and mapped future projections of fire depending upon geographical extents of model boundaries. Only the ecoregion models, accounting for the unique patterns of vegetation, climate, and human infrastructure, projected an increase in fire in most forested regions of the state, congruent with predictions from other studies.

Climate change and California's terrestrial biodiversity.

In this review and synthesis, we argue that California is an important test case for the nation and world because terrestrial biodiversity is very high, present and anticipated threats to biodiversity from climate change and other interacting stressors are severe, and innovative approaches to protecting biodiversity in the context of climate change are being developed and tested. We first review salient dimensions of California's terrestrial physical, biological, and human diversity. Next, we examine four facets of the threat to their sustainability of these dimensions posed by climate change: direct impacts, illustrated by a new analysis of shifting diversity hotspots for plants; interactive effects involving invasive species, land-use change, and other stressors; the impacts of changing fire regimes; and the impacts of land-based renewable energy development. We examine recent policy responses in each of these areas, representing attempts to better protect biodiversity while advancing climate adaptation and mitigation. We conclude that California's ambitious 30 × 30 Initiative and its efforts to harmonize biodiversity conservation with renewable energy development are important areas of progress. Adapting traditional suppression-oriented fire policies to the reality of new fire regimes is an area in which much progress remains to be made.

Damage to tropical forests caused by cyclones is driven by wind speed but mediated by topographical exposure and tree characteristics.

Each year, an average of 45 tropical cyclones affect coastal areas and potentially impact forests. The proportion of the most intense cyclones has increased over the past four decades and is predicted to continue to do so. Yet, it remains uncertain how topographical exposure and tree characteristics can mediate the damage caused by increasing wind speed. Here, we compiled empirical data on the damage caused by 11 cyclones occurring over the past 40 years, from 74 forest plots representing tropical regions worldwide, encompassing field data for 22,176 trees and 815 species. We reconstructed the wind structure of those tropical cyclones to estimate the maximum sustained wind speed (MSW) and wind direction at the studied plots. Then, we used a causal inference framework combined with Bayesian generalised linear mixed models to understand and quantify the causal effects of MSW, topographical exposure to wind (EXP), tree size (DBH) and species wood density (ρ) on the proportion of damaged trees at the community level, and on the probability of snapping or uprooting at the tree level. The probability of snapping or uprooting at the tree level and, hence, the proportion of damaged trees at the community level, increased with increasing MSW, and with increasing EXP accentuating the damaging effects of cyclones, in particular at higher wind speeds. Higher ρ decreased the probability of snapping and to a lesser extent of uprooting. Larger trees tended to have lower probabilities of snapping but increased probabilities of uprooting. Importantly, the effect of ρ decreasing the probabilities of snapping was more marked for smaller than larger trees and was further accentuated at higher MSW. Our work emphasises how local topography, tree size and species wood density together mediate cyclone damage to tropical forests, facilitating better predictions of the impacts of such disturbances in an increasingly windier world.

Pharmacokinetic Similarity of ABP 654, an Ustekinumab Biosimilar Candidate: Results from a Randomized, Double-blind Study in Healthy Subjects.

ABP 654 is a proposed biosimilar to ustekinumab reference product (RP) which works through antagonism of interleukin-12 and interleukin-23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including some forms of plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. A randomized, double-blinded, single-dose, 3-arm, parallel-group study was conducted to assess the pharmacokinetic (PK) similarity of ABP 654 with ustekinumab RP sourced from the United States (US) and the European Union (EU); the PK similarity of ustekinumab US versus ustekinumab EU; and the comparative safety, tolerability, and immunogenicity of all 3 products. A total of 238 healthy subjects were randomized 1:1:1 and stratified by gender and ethnicity (Japanese versus non-Japanese) to receive a single 90 mg subcutaneous injection of ABP 654 or ustekinumab US or ustekinumab EU. PK similarity was established based on 90% confidence intervals (CIs) for the primary endpoints of area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf ) and maximum observed serum concentration (Cmax ) being contained within the prespecified margin of 0.8-1.25. No clinically meaningful differences in immunogenicity were found among the 3 products. Adverse events were similar between treatment groups and consistent with the safety profile of ustekinumab RP. Results indicate that ABP 654, ustekinumab US and ustekinumab EU share similar PK and safety profiles.

Understanding the confluence of injury and obesity in a Grade 2 obesity and above population.

OBJECTIVE: Obesity and injury are major inter-related public health challenges. The objective of this study was to explore the perceptions of injury in people with severe obesity. METHODS: A cross-sectional design was employed to capture injury perception and lifestyle habits via questionnaires. Weight (kg) and height (m) were measured by clinicians for patients attending a weight loss group program. Univariate, chi-square, ANOVA and ordinal regression analyses were undertaken. RESULTS: There were 292 participants (67.1% female), mean age 49.3 years and Body Mass Index 47.2 kg/m2 (range 30.7-91.9 kg/m2). Concern about having an injury was found in 83%, and 74.2% thought that weight would increase the likelihood of injury. A greater concern of being injured at baseline was associated with less weight loss at eight weeks (F=3.567; p=0.03). Depression, anxiety and sleepiness score were higher in those who reported greater 'Concern about having an injury'. CONCLUSIONS: People with obesity fear injury and falling, which limits their willingness to exercise. Anxiety symptoms appear to exacerbate this connection. IMPLICATIONS FOR PUBLIC HEALTH: In individuals with obesity, anxiety, sleepiness and depression are associated with a fear of being injured. Addressing fear and reducing anxiety may decrease barriers to participating in physical activity.

Obesity, lifestyle behaviours and psychological effects of the COVID-19 lockdown: A survey of patients attending a tertiary weight loss clinic.

Lockdown measures due to coronavirus-19 disease (COVID-19) have impacted lifestyle factors. This study aimed to explore whether health and lifestyle behaviours changed during the 2020 COVID-19 lockdown among patients with obesity. A specifically designed online survey and the Depression Anxiety Stress Scale (DASS-21) were administered to patients scheduled to attend a tertiary weight management service between 6 June-12 August 2020. A total of 210 participants completed the survey; mean age (SD) was 52.1 (12.5) years, 69% female and 67% Caucasian. Only 1.4% had tested positive to COVID-19. There was a statistically significant increase in weight pre- and post-COVID-19 lockdown, with no sex differences. Most (61.3%) gained weight, 30.4% lost weight and 8.3% maintained. The majority changed their overall purchasing (88.4%) and eating behaviours (91.6%). Two-thirds (64%) reported they did some form of exercise during the lockdown. Of those, exercise declined in 56.8% and increased in 18%. DASS-21 scores were positively correlated to worry about COVID-19, eating fewer core foods and eating more convenient/treat foods and negatively correlated with exercise. The results provide insights into how and why behaviour change occurs during stressful periods like the COVID-19 pandemic. Although there was variability in individual weight trajectories, on average people with obesity gained weight and changed lifestyle behaviours during the COVID-19 lockdown period. Strategies and support for people with obesity are required at these times.

Making Space in Geographical Analysis.

In this commentary we reflect on the potential and power of geographical analysis, as a set of methods, theoretical approaches, and perspectives, to increase our understanding of how space and place matter for all. We emphasize key aspects of the field, including accessibility, urban change, and spatial interaction and behavior, providing a high-level research agenda that indicates a variety of gaps and routes for future research that will not only lead to more equitable and aware solutions to local and global challenges, but also innovative and novel research methods, concepts, and data. We close with a set of representation and inclusion challenges to our discipline, researchers, and publication outlets.

Progressive resistance training in young people with Prader-Willi syndrome: protocol for a randomised trial (PRESTO).

INTRODUCTION: Preliminary evidence suggests that progressive resistance training may be beneficial for people with Prader-Willi Syndrome (PWS), a rare genetic condition that results in muscle weakness and low muscle tone.To establish whether community-based progressive resistance training is effective in improving the muscle strength of people with PWS; to determine cost-effectiveness; and, to complete a process evaluation assessing intervention fidelity, exploring mechanisms of impact, understanding participant experiences and identifying contextual factors affecting implementation. METHODS AND ANALYSIS: A multisite, randomised controlled trial will be completed. Sixty participants with PWS will be randomised to receive either progressive resistance training (experimental) or non-progressive exercise (placebo control). Participants will be aged 13 to 60 years, be able to follow simple instructions in English and have no contraindications to performing progressive resistance training. The experimental group will complete progressive resistance training two times weekly for 24 weeks supervised by an exercise professional at a community gym. The control group will receive all aspects of the intervention except progressive overload. Outcomes will be assessed at week 25 (primary endpoint) and week 52 by a blinded assessor. The primary outcome is muscle strength assessed using one repetition maximum for upper limb and lower limb. Secondary outcomes are muscle mass, functional strength, physical activity, community participation, health-related quality of life and behaviour. Health economic analysis will evaluate cost-effectiveness. Process evaluation will assess safety and intervention fidelity, investigate mechanism of impact, explore participant experiences and identify contextual factors affecting implementation. Data collection commenced in February 2020 and will conclude in September 2023. ETHICS AND DISSEMINATION: Ethical approval was obtained from The Royal Children's Hospital Human Research Ethics Committee (HREC/50874/RCHM-2019) under the National Mutual Acceptance initiative. Research governance approvals were obtained from five clinical sites. Results will be disseminated through published manuscripts, conference presentations, public seminars and practical resources for stakeholder groups. TRIAL REGISTRATION NUMBER: ACTRN12620000416998; Australian and New Zealand Clinical Trial Registry.

A function-based typology for Earth's ecosystems.

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of 'living in harmony with nature'1,2. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management3. Ecosystems vary in their biota4, service provision5 and relative exposure to risks6, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth's ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework.

Altered cyclone-fire interactions are changing ecosystems.

Global change is altering interactions between ecological disturbances. We review interactions between tropical cyclones and fires that affect woody biomes in many islands and coastal areas. Cyclone-induced damage to trees can increase fuel loads on the ground and dryness in the understory, which increases the likelihood, intensity, and area of subsequent fires. In forest biomes, cyclone-fire interactions may initiate a grass-fire cycle and establish stable open-canopy biomes. In cyclone-prone regions, frequent cyclone-enhanced fires may generate and maintain stable open-canopy biomes (e.g., savannas and woodlands). We discuss how global change is transforming fire and cyclone regimes, extensively altering cyclone-fire interactions. These altered cyclone-fire interactions are shifting biomes away from historical states and causing loss of biodiversity.

Species traits explain public perceptions of human-bird interactions.

The impacts of urbanization on bird biodiversity depend on human-environment interactions that drive land management. Although a commonly studied group, less attention has been given to public perceptions of birds close to home, which can capture people's direct, everyday experiences with urban biodiversity. Here, we used ecological and social survey data collected in the metropolitan region of Phoenix, Arizona, USA, to determine how species traits are related to people's perceptions of local bird communities. We used a trait-based approach to classify birds by attributes that may influence human-bird interactions, including color, size, foraging strata, diet, song, and cultural niche space based on popularity and geographic specificity. Our classification scheme using hierarchical clustering identified four trait categories, labeled as Metropolitan (gray, loud, seedeaters foraging low to ground), Familiar (yellow/brown generalist species commonly present in suburban areas), Distinctive (species with distinguishing appearance and song), and Hummingbird (hummingbird species, small and colorful). Strongly held beliefs about positive or negative traits were also more consistent than ambivalent ones. The belief that birds were colorful and unique to the regional desert environment was particularly important in fortifying perceptions. People largely perceived hummingbird species and birds with distinctive traits positively. Similarly, urban-dwelling birds from the metropolitan trait group were related to negative perceptions, probably due to human-wildlife conflict. Differences arose across sociodemographics (including income, age, education, and Hispanic/Latinx identity), but explained a relatively low amount of variation in perceptions compared with the bird traits present in the neighborhood. Our results highlight how distinctive aesthetics, especially color and song, as well as traits related to foraging and diet drive perceptions. Increasing people's direct experiences with iconic species tied to the region and species with distinguishing attributes has the potential to improve public perceptions and strengthen support for broader conservation initiatives in and beyond urban ecosystems.

Impact of patient characteristics on clinicians' decisions to involve dietitians in eating disorder treatment.

BACKGROUND: Dietetic involvement in eating disorder (ED) treatment is often initiated by other members of a patient's treating team. The present study aimed to examine the impact of patient characteristics on clinicians' decisions to involve a dietitian in a patient's ED treatment, as well as the influence of clinician characteristics on their decision-making. METHODS: ED clinicians were recruited to complete an online survey, which used case vignettes to assess their likelihood of referring patients to a dietitian or consulting with a dietitian for guidance. Questions were also included that measured clinician anxiety, beliefs about the therapy they deliver, beliefs about dietitians and views on evidence-based practice to determine whether these were related to their responses to case vignettes. RESULTS: Fifty-seven clinicians completed the survey, with the largest group being clinical psychologists (n = 22, 39%). ED diagnosis, weight status, medical co-morbidities and progress in treatment were all shown to be influential on whether clinicians involved dietitians in ED treatment. Clinician characteristics and their beliefs about dietitians were generally not correlated with the likelihood of seeking dietetic input. CONCLUSIONS: The present study indicates that clinicians' decisions to involve dietitians in ED treatment are systematic rather than random decisions influenced by individual clinician characteristics. Clinicians require further education on the potential for malnutrition regardless of patients' ED diagnosis or weight status, and the dietitian's role in addressing this.

Discrepancies Between Australian Eating Disorder Clinicians and Consumers Regarding Essential Components of Dietetic Treatment.

BACKGROUND: A recent Delphi study indicated that, compared with eating disorder (ED) consumers and carers, ED specialists were less likely to endorse involvement of a dietitian as a standard component of treatment. In addition, there was disagreement between these groups regarding the inclusion of a number of components of dietetic treatment. OBJECTIVE: This study aimed to further investigate these data to identify areas of disagreement among ED specialist dietitians, ED specialist non-dietetic clinicians, consumers, and carers with regard to outpatient dietetic treatment. DESIGN AND PARTICIPANTS/SETTING: The ED specialists panel from a previous Delphi study was recoded into 2 panels: ED specialist dietitians (n = 31) and ED specialist non-dietetic clinicians (n = 48) to compare responses of these panels with responses from consumers (n = 32) and carers (n = 23). MAIN OUTCOME MEASURES: Statements in 7 categories relating to referral to dietitian, essential components of outpatient dietetic treatment regarding 4 ED patient populations, strategies to promote multidisciplinary collaboration, and skills dietitians should possess if treating patients with an ED were rated on a 5-point Likert scale. STATISTICAL ANALYSIS PERFORMED: One-way analysis of variance was conducted with post-hoc multiple comparisons to compare mean statement ratings. RESULTS: Thirty-seven statements (30%) showed statistically significant differences (P < .05) in responses between panels. Discrepancies were primarily observed for statements regarding how and when dietetics is included in treatment and essential components of dietetic treatment, particularly the use of behavioral tasks, such meal plans and self-monitoring. Results also highlighted deficits in participants' understanding of core responsibilities of dietitians in ED treatment and dietitians "drifting" from delivering evidence-based components of dietetic treatment. CONCLUSIONS: Results of this study show discrepancies among ED dietitians, clinicians, consumers, and carers regarding what dietetic treatment for people with EDs should encompass. It also indicates the need for further research into optimizing dietetic treatment for EDs that is conducted in collaboration with individuals with lived experience.

A Review of the Totality of Evidence for the Development and Approval of ABP 710 (AVSOLA), an Infliximab Biosimilar.

ABP 710 (AVSOLA®) is a biosimilar to infliximab reference product (RP), a monoclonal antibody targeting tumor necrosis factor alpha (TNFα). It is approved in the USA and Canada for all the same indications as infliximab RP. Approval of ABP 710 was based on the totality of evidence (TOE) generated using a stepwise approach to assess its similarity with infliximab RP with regard to analytical (structural and functional) characteristics, pharmacokinetic parameters, and clinical efficacy and safety. ABP 710 was shown to be analytically similar to infliximab RP including in amino acid sequence, primary peptide structure, and glycan mapping and purity. ABP 710 was also demonstrated to be similar to infliximab RP with regard to functional characterization including in vitro binding, effector functions, and signaling pathways important for the mechanisms of action for clinical efficacy in multiple indications of immune-mediated inflammatory disorders including inflammatory bowel disease (IBD), especially binding to both soluble and membrane-bound TNFα. Pharmacokinetic similarity of ABP 710 with infliximab RP was demonstrated in healthy volunteers following a single 5 mg/kg intravenous dose. Comparative clinical efficacy of ABP 710 with infliximab RP was demonstrated in patients with rheumatoid arthritis. Safety and immunogenicity were also demonstrated to be similar for both ABP 710 and the RP. Overall, the TOE supported the conclusion that ABP 710 is highly similar to infliximab RP and supported scientific justification for extrapolation to all approved indications of infliximab RP, including IBD.

Efficacy and safety of blinatumomab: Post hoc pooled analysis in Asian adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

BACKGROUND: Global studies have demonstrated the efficacy and safety of blinatumomab-a BiTE® (bispecific T-cell engager) targeted immuno-oncology therapy that mediates the lysis of cells expressing CD19 in patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Because limited data are available in Asian patients, we conducted a post hoc pooled analysis in 45 Asian adult patients with R/R ALL-19 from the blinatumomab arm of TOWER (NCT02013167) and 26 from Study 265, a phase 1b/2 study in Japanese adults (NCT02412306). METHODS: Patients received a maximum of two cycles of induction blinatumomab for 4 weeks by continuous intravenous infusion (cycle 1/week 1: 9 µg/day; cycle 1/weeks 2-4: 28 µg/day) followed by 2 weeks of no blinatumomab (each 6-week cycle); patients received 28 µg/day blinatumomab in subsequent cycles. RESULTS: Twenty of 45 patients enrolled (44%) achieved complete remission with full or partial hematologic recovery compared with 44% in TOWER and 80% and 38% in phase 1b and phase 2, respectively, of Study 265. The Kaplan-Meier (KM) median overall survival was 11.9 months (95% confidence interval [CI], 9.9-17.1) and the KM median duration of relapse-free survival was 8.9 months (95% CI, 3.8-10.7). Ninety-three percent of patients had grade ≥ 3 treatment-emergent adverse events (AEs) compared with 87% in TOWER and 80% and 100% in phase 1b and phase 2, respectively, of Study 265. Five patients (11.4%) had fatal AEs. CONCLUSIONS: The safety and efficacy of blinatumomab in Asian patients were comparable with those reported in previous global studies with no new safety signals.