Dynamics of technology emergence in innovation networks.

To create the next innovative product, participants in science need to understand which existing technologies can be combined, what new science must be discovered, and what new technologies must be invented. Knowledge of these often arrives by means of expert consensus or popularity metrics, masking key information on how intellectual efforts accumulate into technological progress. To address this shortcoming, we first present a method to establish a mathematical link between technological evolution and complex networks: a path of events that narrates innovation bottlenecks. Next, we quantify the position and proximity of documents to these innovation paths. The result is an innovation network that more exhaustively captures deterministic knowledge flows with respect to a marketed innovative product. Our dataset, containing over three million biomedical citations, demonstrates the possibility of quantifying the accumulation, speed, and division of labour in innovation over a sixty-year time horizon. The significance of this study includes the (i) use of a purpose-generated dataset showing causal paths from research to development to product; (ii) analysis of the innovation process as a directed acyclic graph; (iii) comparison between calendar time and network time; (iv) ordering of science funders along technology lifecycles; (v) quantification of innovative activities' importance to an innovative outcome; and (vi) integration of publication, patent, clinical trial, regulatory data to study innovation holistically.

The Attitudes of Patients Toward Orthopaedic Post-surgical Scars.

Background Post-surgical scars (PSS) are an expected consequence of surgery. Several factors have previously been associated with PSS satisfaction including patient age and time elapsed post-operative. Little data are available regarding patient attitudes toward orthopaedic PSS. Knowledge of patient attitudes and the various associated factors may allow physicians to administer peri-operative care to mitigate the potential negative effects of PSS. Our study aims to investigate the attitudes of patients toward their PSS using quantitative scar assessment scales and to identify factors associated with PSS satisfaction. Methods We conducted a retrospective study with a follow-up. We included all patients with orthopaedic PSS on their upper or lower limbs between two and 18 weeks postoperative attending Cork University Hospital, Ireland, between February and August 2022. Patients completed an initial baseline questionnaire and then a follow-up questionnaire six months post-operative. The Patient and Observer Scar Assessment Scale (POSAS) evaluated PSS satisfaction. The European Quality of Life 5 Domain (EQ-5D), alongside several Likert scales, evaluated the patient's quality of life (QoL). Results In total, 91 patients were included. The mean POSAS score was 28.41 (95% CI, 25.85-30.97). Younger patient age (p=0.045) and decreased time passed post-operatively (p=0.002) were associated with poorer PSS satisfaction. Patients reporting their PSS appearing worse than expected were more likely to agree that their QoL had been adversely affected by it (p=0.001). Conclusion Most patients were satisfied with their orthopaedic PSS. This study identified several factors associated with poor PSS satisfaction. Our finding, which associated patient scar expectations and QoL, is novel and has not been previously examined. Accordingly, peri-operative interventions, including scar expectation management, may be implemented to mitigate scar-related QoL impact.

Preferences for potential benefits and risks for gene therapy in the treatment of sickle cell disease.

Objective of this study is to quantify benefit-risk tradeoffs pertaining to potential gene therapies among adults and parents/caregivers of children with sickle cell disease (SCD). A discrete-choice experiment survey was developed in which respondents selected their preferred treatment alternatives in a series of experimentally controlled pairs of hypothetical gene therapies and a "no gene therapy" option. Gene therapy alternatives were defined based on the chance of eliminating SCD symptoms, expected increases in life expectancy they could offer, treatment-related risk of death, and potential increases in lifetime cancer risk. Respondents made selections based on their current disease severity and in the context of expectations of worsened disease. Three clinical sites and 1 patient organization recruited 174 adult patients and 109 parents of children with SCD to complete the survey. Adult and parent respondents were generally willing to choose gene therapies, but the adults required higher expected levels of efficacy (ie, higher chance of eliminating symptoms) than parents to choose gene therapies that conferred mortality risks of ≥10%. When adults and parents of children with less severe symptoms were asked to consider scenarios of higher levels of disease severity, the increased risk tolerance, and the lowest acceptable level of efficacy for gene therapies with mortality risks dropped by >50%. Baseline SCD symptoms are a major driver of gene therapy acceptability. Adults and parents of patients with milder symptoms may prefer other treatment options; however, an expectation of symptoms deterioration triggers strong reassessment of the acceptable benefit-risk balance of this novel technology.

Unveiling and harnessing the human gut microbiome in the rising burden of non-communicable diseases during urbanization.

The world is witnessing a global increase in the urban population, particularly in developing Asian and African countries. Concomitantly, the global burden of non-communicable diseases (NCDs) is rising, markedly associated with the changing landscape of lifestyle and environment during urbanization. Accumulating studies have revealed the role of the gut microbiome in regulating the immune and metabolic homeostasis of the host, which potentially bridges external factors to the host (patho-)physiology. In this review, we discuss the rising incidences of NCDs during urbanization and their links to the compositional and functional dysbiosis of the gut microbiome. In particular, we elucidate the effects of urbanization-associated factors (hygiene/pollution, urbanized diet, lifestyles, the use of antibiotics, and early life exposure) on the gut microbiome underlying the pathogenesis of NCDs. We also discuss the potential and feasibility of microbiome-inspired and microbiome-targeted approaches as novel avenues to counteract NCDs, including fecal microbiota transplantation, diet modulation, probiotics, postbiotics, synbiotics, celobiotics, and precision antibiotics.

Structural Origins of Viscosity in Imidazolium and Pyrrolidinium Ionic Liquids Coupled with the NTf2- Anion.

Ionic liquid viscosity is one of the most important properties to consider for practical applications. Yet, the connection between local structure and viscosity remains an open question. This article explores the structural origin of differences in the viscosity and viscoelastic relaxation across several ionic liquids, including cations with alkyl, ether, and thioether tails, of the imidazolium and pyrrolidinium families coupled with the NTf2- anion. In all cases, for the systems studied here, we find that pyrrolidinium-based ions are "harder" than their imidazolium-based counterparts. We make a connection between the chemical concept of hardness vs softness and specific structural and structural dynamic quantities that can be derived from scattering experiments and simulations.

Adaptation of the WOMAC for Use in a Patient Preference Study.

OBJECTIVES: To adapt a patient-reported outcome (PRO) measure, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), into efficacy attributes for a discrete choice experiment (DCE) survey designed to quantify the relative importance of endpoints commonly used in knee osteoarthritis (KOA) trials. METHODS: The adaptation comprised four steps: (1) selecting domains of interest; (2) determining presentation and framing of selected attributes; (3) determining attribute levels; and (4) developing choice tasks. This process involved input from multiple stakeholders, including regulators, health preference researchers, and patients. Pretesting was conducted to evaluate if patients comprehended the adapted survey attributes and could make trade-offs among them. RESULTS: The WOMAC pain and function domains were selected for adaption to two efficacy attributes. Two versions of the discrete choice experiment (DCE) instrument were created to compare efficacy using (1) total domain scores and (2) item scores for "walking on a flat surface." Both attributes were presented as improvement from baseline scores by levels of 0%, 30%, 50%, and 100%. Twenty-six participants were interviewed in a pretest of the instrument (average age 60 years; 58% female; 62% had KOA for ≥ 5 years). The participants found both versions of attributes meaningful and relevant for treatment decision-making. They demonstrated willingness and ability to tradeoff improvements in pain and function separately, though many perceived them as inter-related. CONCLUSIONS: This study adds to the growing literature regarding adapting PRO measures for patient preference studies. Such adaptation is important for designing a preference study that can incorporate a clinical trial's outcomes with PRO endpoints.

Quantitative Benefit-Risk Assessment in Medical Product Decision Making: A Good Practices Report of an ISPOR Task Force.

Benefit-risk assessment is commonly conducted by drug and medical device developers and regulators, to evaluate and communicate issues around benefit-risk balance of medical products. Quantitative benefit-risk assessment (qBRA) is a set of techniques that incorporate explicit outcome weighting within a formal analysis to evaluate the benefit-risk balance. This report describes emerging good practices for the 5 main steps of developing qBRAs based on the multicriteria decision analysis process. First, research question formulation needs to identify the needs of decision makers and requirements for preference data and specify the role of external experts. Second, the formal analysis model should be developed by selecting benefit and safety endpoints while eliminating double counting and considering attribute value dependence. Third, preference elicitation method needs to be chosen, attributes framed appropriately within the elicitation instrument, and quality of the data should be evaluated. Fourth, analysis may need to normalize the preference weights, base-case and sensitivity analyses should be conducted, and the effect of preference heterogeneity analyzed. Finally, results should be communicated efficiently to decision makers and other stakeholders. In addition to detailed recommendations, we provide a checklist for reporting qBRAs developed through a Delphi process conducted with 34 experts.

Use of Bayesian decision analysis to maximize value in patient-centered randomized clinical trials in Parkinson's disease.

A fixed one-sided significance level of 5% is commonly used to interpret the statistical significance of randomized clinical trial (RCT) outcomes. While it is necessary to reduce the false positive rate, the threshold used could be chosen quantitatively and transparently to specifically reflect patient preferences regarding benefit-risk tradeoffs as well as other considerations. How can patient preferences be explicitly incorporated into RCTs in Parkinson's disease (PD), and what is the impact on statistical thresholds for device approval? In this analysis, we apply Bayesian decision analysis (BDA) to PD patient preference scores elicited from survey data. BDA allows us to choose a sample size (n) and significance level (α) that maximizes the overall expected value to patients of a balanced two-arm fixed-sample RCT, where the expected value is computed under both null and alternative hypotheses. For PD patients who had previously received deep brain stimulation (DBS) treatment, the BDA-optimal significance levels fell between 4.0% and 10.0%, similar to or greater than the traditional value of 5%. Conversely, for patients who had never received DBS, the optimal significance level ranged from 0.2% to 4.4%. In both of these populations, the optimal significance level increased with the severity of the patients' cognitive and motor function symptoms. By explicitly incorporating patient preferences into clinical trial designs and the regulatory decision-making process, BDA provides a quantitative and transparent approach to combine clinical and statistical significance. For PD patients who have never received DBS treatment, a 5% significance threshold may not be conservative enough to reflect their risk-aversion level. However, this study shows that patients who previously received DBS treatment present a higher tolerance to accept therapeutic risks in exchange for improved efficacy which is reflected in a higher statistical threshold.

Illustrating Emerging Good Practices for Quantitative Benefit-Risk Assessment: A Hypothetical Case Study of Systemic Biologic Treatments for Plaque Psoriasis.

OBJECTIVES: Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force's recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval. The qBRA evaluated 2 dosing regimens of brodalumab (210 mg or 140 mg twice weekly) compared with weight-based dosing of ustekinumab and placebo. METHODS: We followed the 5 steps recommended by the Task Force. Attributes included treatment response (≥75% improvement in Psoriasis Area and Severity Index), suicidal ideation and behavior, and infections. Performance data were drawn from pivotal clinical trials of brodalumab. The qBRA used multicriteria decision analysis and preference weights from a hypothetical discrete choice experiment. Sensitivity analyses examined the robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, consideration of a subgroup (nail psoriasis), and the maintenance phase of treatment (52 weeks instead of 12). RESULTS: Results from this hypothetical qBRA suggest that brodalumab 210 mg had a more favorable benefit-risk profile compared with ustekinumab and placebo. Ranking of brodalumab compared with ustekinumab was dependent on brodalumab's dose. Sensitivity analyses demonstrated robustness of benefit-risk ranking to uncertainty in clinical effect and preference estimates, as well as choice of attributes and length of follow-up. CONCLUSION: This case study demonstrates how to implement the ISPOR Task Force's good practice recommendations on qBRA.

Outpatient purchasing patterns of hydroxychloroquine and ivermectin in the USA and Canada during the COVID-19 pandemic: an interrupted time series analysis from 2016 to 2021.

BACKGROUND: Hydroxychloroquine and ivermectin received widespread attention after initial studies suggested that they were effective against COVID-19. However, several of these studies were later discredited. OBJECTIVES: We explored the impact of scientific articles, public announcements and social media posts on hydroxychloroquine and ivermectin purchases in the USA and Canada during the COVID-19 pandemic. METHODS: We conducted a retrospective, population-based time series analysis of retail hydroxychloroquine and ivermectin purchases in the USA and Canada from February 2016 through to December 2021, using IQVIA's Multinational Integrated Data Analysis database. We fitted the purchasing rates with interventional autoregressive integrated moving average models. We used Google Trends to identify the most influential interventions to include in the models. RESULTS: There were significant pulse increases in hydroxychloroquine purchases in March 2020 in both the USA (P < 0.0001) and Canada (P < 0.0001). For ivermectin, there were no significant changes in April 2020 in either the USA (P = 0.41) or Canada (P = 0.16); however, significant pulse increases occurred from December 2020 to January 2021 in both the USA (P = 0.0006) and Canada (P < 0.0001), as well as significant ramp increases from April to August 2021 in both the USA (P < 0.0001) and Canada (P = 0.02). The increases in ivermectin purchases were larger in the USA than in Canada. CONCLUSIONS: Increases in hydroxychloroquine and ivermectin purchasing rates aligned with controversial scientific articles and social media posts. This highlights the importance of scientific integrity and disseminating accurate epidemiologic information during pandemics.

Preferences for Risks and Benefits of Islet Cell Transplantation for Persons With Type 1 Diabetes With History of Episodes of Severe Hypoglycemia: A Discrete-Choice Experiment to Inform Regulatory Decisions.

BACKGROUND: The advisory panel for US Food and Drug Administration (FDA) recently endorsed pancreatic islet cell transplantation (ICT) therapy for suboptimally controlled type 1 diabetes (T1D), and FDA approval is under consideration. An important part of regulatory approval includes the patient perspective, through discrete choice. We developed a discrete-choice instrument and used it to determine how 90 people with T1D weigh the risks and benefits of ICT to inform regulatory decisions. METHODS: Sawtooth software created a random, full-profile, balanced-overlap experimental design for a measure with 8 attributes of ICT risks/benefits, each with 3 to 5 levels. We asked 18 random task pairs, sociodemographics, diabetes management, and hypoglycemia questions. Analysis was performed using random parameters logistic regression technique. RESULTS: The strongest preference was for avoiding the highest chance (15%) of serious procedure-related complications (ß = -2.03, P < 0.001). The strongest positive preference was for gaining 5-y insulin independence (ß = 1.75, P < 0.001). The desire for 5-y HbA1C-defined clinical treatment success was also strong (ß = 1.39, P < 0.001). Subgroup analysis suggested strong gender differences with women showing much higher preferences for all benefits (68% higher for 5-y insulin independence), and men were generally more risk averse than women. Those with high versus low diabetes distress showed 3 times stronger preference for 5-y insulin independence but also twice preference to avoid risks of serious complications. CONCLUSIONS: Despite showing the most preference for avoiding serious ICT complications, people with T1D had a strong preference for achieving ICT benefits, especially insulin independence. We identified important attributes of ICT and demonstrated that patients are willing to make these trade-offs, showing support for the introduction of ICT.

Patient-Centered Identification of Meaningful Regulatory Endpoints for Medical Devices to Treat Parkinson's Disease.

Introduction. A growing literature has developed on identifying outcomes that matter to patients. This study demonstrates an approach involving patient and regulatory perspectives to identify outcomes that are meaningful in the context of medical devices for Parkinson's disease (PD). Methods. A systematic process was used for specifying relevant regulatory endpoints by synthesizing inputs of various sources and stakeholders. First, a literature review was conducted to identify important benefits, risks, and other considerations for medical devices to treat PD; patient discussion groups (n = 6) were conducted to refine the list of considerations, followed by a survey (n = 29) to prioritize them; and patient and Food and Drug Administration (FDA) reviewers informed specification of the final endpoints. Two FDA clinicians gave clinical and regulatory perspectives at each step. Results. Movement symptoms were ranked as most important (ranked 1 or 2 by 72% of participants) and psychological and cognitive symptoms as the next most important (ranked 1 or 2 by 52% of participants). Within movement symptoms, falls, impaired movement, bradykinesia, resting tremor, stiffness, and rigidity were ranked highly. Overall, nine attributes were identified and prioritized as patient-centric for use in clinical trial design and quantitative patient preference studies. These attributes were benefits and risks related to therapeutics for PD as well as other considerations, including time until a medical device is available for patient use. Discussion. This prospective approach identified meaningful and relevant benefits, risks, and other considerations that may be used for clinical trial design and quantitative patient preference studies. Although PD was the focus of this study, the approach can be used to study patient perspectives about other disease or treatment areas.

Parkinson's Patients' Tolerance for Risk and Willingness to Wait for Potential Benefits of Novel Neurostimulation Devices: A Patient-Centered Threshold Technique Study.

Background. Parkinson's disease (PD) is neurodegenerative, causing motor, cognitive, psychological, somatic, and autonomic symptoms. Understanding PD patients' preferences for novel neurostimulation devices may help ensure that devices are delivered in a timely manner with the appropriate level of evidence. Our objective was to elicit preferences and willingness-to-wait for novel neurostimulation devices among PD patients to inform a model of optimal trial design. Methods. We developed and administered a survey to PD patients to quantify the maximum levels of risks that patients would accept to achieve potential benefits of a neurostimulation device. Threshold technique was used to quantify patients' risk thresholds for new or worsening depression or anxiety, brain bleed, or death in exchange for improvements in "on-time," motor symptoms, pain, cognition, and pill burden. The survey elicited patients' willingness to wait to receive treatment benefit. Patients were recruited through Fox Insight, an online PD observational study. Results. A total of 2740 patients were included and a majority were White (94.6%) and had a 4-year college degree (69.8%). Risk thresholds increased as benefits increased. Threshold for depression or anxiety was substantially higher than threshold for brain bleed or death. Patient age, ambulation, and prior neurostimulation experience influenced risk tolerance. Patients were willing to wait an average of 4 to 13 years for devices that provide different levels of benefit. Conclusions. PD patients are willing to accept substantial risks to improve symptoms. Preferences are heterogeneous and depend on treatment benefit and patient characteristics. The results of this study may be useful in informing review of device applications and other regulatory decisions and will be input into a model of optimal trial design for neurostimulation devices.

Review article: fungal alterations in inflammatory bowel diseases.

BACKGROUND: Emerging data suggest that alterations in gut fungi may be associated with the pathogenesis of inflammatory bowel disease (IBD). In healthy individuals, gut commensal fungi act synergistically with other members of the microbiota to maintain homeostasis but their role in IBD is less clear. AIM: To review the role of gut fungi and their trans-kingdom interactions with bacteria in IBD METHODS: A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies that have reported fungi and IBD. RESULTS: There is an increased total fungal load particularly of Candida and Malassezia species in the faeces and mucosa of Crohn's disease patients, and a lower fungal diversity in the faeces of ulcerative colitis patients. Caspase recruitment domain-containing protein (CARD)-9 polymorphism in Crohn's disease patients favours Malassezia colonisation that worsens gut inflammation. Diet high in carbohydrates increased the total abundance of Candida species, whereas protein-rich diet had the opposite effect. Anti-fungal therapies are mostly used to treat Candida albicans or Histoplasma capsulatum infections in IBD, whereas pilot studies of supplementing fungal probiotics Saccharomycopsis fibuligera, Saccharomyces boulardii and Saccharomyces cerevisiae CNCM I-3856 strain showed therapeutic effects in IBD. CONCLUSIONS: Gut fungi are altered in patients with Crohn's disease and ulcerative colitis. Modulation of the fungal microbiota can be considered as a therapeutic approach for IBD. Future research should focus on understanding how the fungal microbiota interacts with other components of the gut microbiota in association with the pathogenesis and development of IBD.

Integrating Quality of Life and Survival Outcomes in Cardiovascular Clinical Trials.

Background Survival and health status (eg, symptoms and quality of life) are key outcomes in clinical trials of heart failure treatment. However, health status can only be recorded on survivors, potentially biasing treatment effect estimates when there is differential survival across treatment groups. Joint modeling of survival and health status can address this bias. Methods and Results We analyzed patient-level data from the PARTNER 1B trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement versus standard care. Health status was quantified with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at randomization, 1, 6, and 12 months. We compared hazard ratios for survival and mean differences in KCCQ scores at 12 months using several models: the original growth curve model for KCCQ scores (ignoring death), separate Bayesian models for survival and KCCQ scores, and a Bayesian joint longitudinal-survival model fit to either 12 or 30 months of survival follow-up. The benefit of transcatheter aortic valve replacement on 12-month KCCQ scores was greatest in the joint-model fit to all survival data (mean difference, 33.7 points; 95% credible intervals [CrI], 24.2-42.4), followed by the joint-model fit to 12 months of survival follow-up (32.3 points; 95% CrI, 22.5-41.5), a Bayesian model without integrating death (30.4 points; 95% CrI, 21.4-39.3), and the original growth curve model (26.0 points; 95% CI, 18.7-33.3). At 12 months, the survival benefit of transcatheter aortic valve replacement was also greater in the joint model (hazard ratio, 0.50; 95% CrI, 0.32-0.73) than in the nonjoint Bayesian model (0.54; 95% CrI, 0.37-0.75) or the original Kaplan-Meier estimate (0.55; 95% CI, 0.40-0.74). Conclusions In patients with severe symptomatic aortic stenosis and prohibitive surgical risk, the estimated benefits of transcatheter aortic valve replacement on survival and health status compared with standard care were greater in joint Bayesian models than other approaches.

Patient-centered clinical trials.

We apply Bayesian decision analysis (BDA) to incorporate patient preferences in the regulatory approval process for new therapies. By assigning weights to type I and type II errors based on patient preferences, the significance level (α) and power (1-ß) of a randomized clinical trial (RCT) for a new therapy can be optimized to maximize the value to current and future patients and, consequently, to public health. We find that for weight-loss devices, potentially effective low-risk treatments have optimal αs larger than the traditional one-sided significance level of 5%, whereas potentially less effective and riskier treatments have optimal αs below 5%. Moreover, the optimal RCT design, including trial size, varies with the risk aversion and time-to-access preferences and the medical need of the target population.

A Framework for Incorporating Patient Preferences Regarding Benefits and Risks into Regulatory Assessment of Medical Technologies.

BACKGROUND: In response to 2012 guidance in which the US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) stated the importance of patient-centric measures in regulatory benefit-risk assessments, the Medical Device Innovation Consortium (MDIC) initiated a project. The project was used to develop a framework to help the Food and Drug Administration (FDA) and industry sponsors understand how patient preferences regarding benefit and risk might be integrated into the review of innovative medical devices. METHODS: A public-private partnership of experts from medical device industry, government, academia and non-profits collaborated on development of the MDIC patient centered benefit-risk framework. RESULTS: The MDIC Framework examines what patient preference information is and the potential use and value of patient preference information in the regulatory process and across the product development life cycle. The MDIC Framework also includes a catalog of patient preference assessment methods and an agenda for future research to advance the field. CONCLUSIONS: This article discusses key concepts in patient preference assessment of particular importance for regulators and researchers that are addressed in the MDIC Framework for patient centered benefit-risk assessment as well as the unique public-private collaboration that led its development.

Joint Estimation of Treatment and Placebo Effects in Clinical Trials with Longitudinal Blinding Assessments.

In some therapeutic areas, treatment evaluation is frequently complicated by a possible placebo effect (i.e., the psychobiological effect of a patient's knowledge or belief of being treated). When a substantial placebo effect is likely to exist, it is important to distinguish the treatment and placebo effects in quantifying the clinical benefit of a new treatment. These causal effects can be formally defined in a joint causal model that includes treatment (e.g., new versus placebo) and treatmentality (i.e., a patient's belief or mentality about which treatment she or he has received) as separate exposures. Information about the treatmentality exposure can be obtained from blinding assessments, which are increasingly common in clinical trials where blinding success is in question. Assuming that treatmentality has a lagged effect and is measured at multiple time points, this article is concerned with joint evaluation of treatment and placebo effects in clinical trials with longitudinal follow-up, possibly with monotone missing data. We describe and discuss several methods adapted from the longitudinal causal inference literature, apply them to a weight loss study, and compare them in simulation experiments that mimic the weight loss study.

Shape-Dependent Interactions of Palladium Nanocrystals with Hydrogen.

Elucidation of the nature of hydrogen interactions with palladium nanoparticles is expected to play an important role in the development of new catalysts and hydrogen-storage nanomaterials. A facile scaled-up synthesis of uniformly sized single-crystalline palladium nanoparticles with various shapes, including regular nanocubes, nanocubes with protruded edges, rhombic dodecahedra, and branched nanoparticles, all stabilized with a mesoporous silica shell is developed. Interaction of hydrogen with these nanoparticles is studied by using temperature-programmed desorption technique and by performing density functional theory modeling. It is found that due to favorable arrangement of Pd atoms on their surface, rhombic dodecahedral palladium nanoparticles enclosed by {110} planes release a larger volume of hydrogen and have a lower desorption energy than palladium nanocubes and branched nanoparticles. These results underline the important role of {110} surfaces in palladium nanoparticles in their interaction with hydrogen. This work provides insight into the mechanism of catalysis of hydrogenation/dehydrogenation reactions by palladium nanoparticles with different shapes.