Instant clot forming and antibacterial wound dressings: Achieving hemostasis in trauma injuries with S-nitroso-N-acetylpenicillamine-tranexamic acid-propolis formulation.

Wound infection and excessive blood loss are the two major challenges associated with trauma injuries that account for 10% of annual deaths in the United States. Nitric oxide (NO) is a gasotransmitter cell signaling molecule that plays a crucial role in the natural wound healing process due to its antibacterial, anti-inflammatory, cell proliferation, and tissue remodeling abilities. Tranexamic acid (TXA), a prothrombotic agent, has been used topically and systemically to control blood loss in reported cases of epistaxis and combat-related trauma injuries. Its properties could be incorporated in wound dressings to induce immediate clot formation, which is a key factor in controlling excessive blood loss. This study introduces a novel, instant clot-forming NO-releasing dressing, and fabricated using a strategic bi-layer configuration. The layer adjacent to the wound was designed with TXA suspended on a resinous bed of propolis, which is a natural bioadhesive possessing antibacterial and anti-inflammatory properties. The base layer, located furthest away from the wound, has an NO donor, S-nitroso-N-acetylpenicillamine (SNAP), embedded in a polymeric bed of Carbosil®, a copolymer of polycarbonate urethane and silicone. Propolis was integrated with a uniform layer of TXA in variable concentrations: 2.5, 5.0, and 7.5 vol % of propolis. This design of the TXA-SNAP-propolis (T-SP) wound dressing allows TXA to form a more stable clot by preventing the lysis of fibrin. The lactate dehydrogenase-based platelet adhesion assay showed an increase in fibrin activation with 7.5% T-SP as compared with control within the first 15 min of its application. A scanning electron microscope (SEM) confirmed the presence of a dense fibrin network stabilizing the clot for fabricated dressing. The antibacterial activity of NO and propolis resulted in a 98.9 ± 1% and 99.4 ± 1% reduction in the colony-forming unit of Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii, respectively, which puts forward the fabricated dressing as an emergency first aid for traumatic injuries, preventing excessive blood loss and soil-borne infections.

Transcriptional changes during crown-root development and emergence in barley (Hordeum vulgare L.).

BACKGROUND: Roots play an important role during plant growth and development, ensuring water and nutrient uptake. Understanding the mechanisms regulating their initiation and development opens doors towards root system architecture engineering. RESULTS: Here, we investigated by RNA-seq analysis the changes in gene expression in the barley stem base of 1 day-after-germination (DAG) and 10DAG seedlings when crown roots are formed. We identified 2,333 genes whose expression was lower in the stem base of 10DAG seedlings compared to 1DAG seedlings. Those genes were mostly related to basal cellular activity such as cell cycle organization, protein biosynthesis, chromatin organization, cytoskeleton organization or nucleotide metabolism. In opposite, 2,932 genes showed up-regulation in the stem base of 10DAG seedlings compared to 1DAG seedlings, and their function was related to phytohormone action, solute transport, redox homeostasis, protein modification, secondary metabolism. Our results highlighted genes that are likely involved in the different steps of crown root formation from initiation to primordia differentiation and emergence, and revealed the activation of different hormonal pathways during this process. CONCLUSIONS: This whole transcriptomic study is the first study aiming at understanding the molecular mechanisms controlling crown root development in barley. The results shed light on crown root emergence that is likely associated with a strong cell wall modification, death of the cells covering the crown root primordium, and the production of defense molecules that might prevent pathogen infection at the site of root emergence.

Structural and functional characterization of sulfurtransferase from Frondihabitans sp. PAMC28461.

Sulfurtransferases transfer of sulfur atoms from thiols to acceptors like cyanide. They are categorized as thiosulfate sulfurtransferases (TSTs) and 3-mercaptopyruvate sulfurtransferases (MSTs). TSTs transfer sulfur from thiosulfate to cyanide, producing thiocyanate. MSTs transfer sulfur from 3-mercaptopyruvate to cyanide, yielding pyruvate and thiocyanate. The present study aimed to isolate and characterize the sulfurtransferase FrST from Frondihabitans sp. PAMC28461 using biochemical and structural analyses. FrST exists as a dimer and can be classified as a TST rather than an MST according to sequence-based clustering and enzyme activity. Furthermore, the discovery of activity over a wide temperature range and the broad substrate specificity exhibited by FrST suggest promising prospects for its utilization in industrial applications, such as the detoxification of cyanide.

Membrane-coated glass electrodes for stable, low-noise electrophysiology recordings in Drosophila central neurons.

BACKGROUND: Electrophysiological recording with glass electrodes is one of the best techniques to measure membrane potential dynamics and ionic currents of voltage-gated channels in neurons. However, artifactual variability of the biophysical state variables that determine recording quality can be caused by insufficient affinity between the electrode and cell membrane during the recording. NEW METHOD: We introduce a phospholipid membrane coating on glass electrodes to improve intracellular electrophysiology recording quality. Membrane-coated electrodes were prepared with a tip-dip protocol for perforated-patch, sharp-electrode current-clamp, and cell-attached patch-clamp recordings from specific circadian clock neurons in Drosophila. We perform quantitative comparisons based on the variability of functional biophysical parameters used in various electrophysiological methods, and advanced statistical comparisons based on the degree of stationariness and signal-to-noise ratio. RESULTS: Results indicate a dramatic reduction in artifactual variabilities of functional parameters from enhanced stability. We also identify significant exclusions of a statistically estimated noise component in a time series of membrane voltage signals, improving signal-to-noise ratio. COMPARISON WITH EXISTING METHODS: Compared to standard glass electrodes, using membrane-coated glass electrodes achieves improved recording quality in intracellular electrophysiology. CONCLUSIONS: Electrophysiological recordings from Drosophila central neurons can be technically challenging, however, membrane-coated electrodes will possibly be beneficial for reliable data acquisition and improving the technical feasibility of axonal intracellular activities measurements and single-channel recordings. The improved electrical stability of the recordings should also contribute to increased mechanical stability, thus facilitating long-term stable measurements of neural activity. Therefore, it is possible that membrane-coated electrodes will be useful for any model system.

Engineered ice-binding protein (FfIBP) shows increased stability and resistance to thermal and chemical denaturation compared to the wildtype.

Many polar organisms produce antifreeze proteins (AFPs) and ice-binding proteins (IBPs) to protect themselves from ice formation. As IBPs protect cells and organisms, the potential of IBPs as natural or biological cryoprotective agents (CPAs) for the cryopreservation of animal cells, such as oocytes and sperm, has been explored to increase the recovery rate after freezing-thawing. However, only a few IBPs have shown success in cryopreservation, possibly because of the presence of protein denaturants, such as dimethyl sulfoxide, alcohols, or ethylene glycol, in freezing buffer conditions, rendering the IBPs inactive. Therefore, we investigated the thermal and chemical stability of FfIBP isolated from Antarctic bacteria to assess its suitability as a protein-based impermeable cryoprotectant. A molecular dynamics (MD) simulation identified and generated stability-enhanced mutants (FfIBP_CC1). The results indicated that FfIBP_CC1 displayed enhanced resistance to denaturation at elevated temperatures and chemical concentrations, compared to wildtype FfIBP, and was functional in known CPAs while retaining ice-binding properties. Given that FfIBP shares an overall structure similar to DUF3494 IBPs, which are recognized as the most widespread IBP family, these findings provide important structural information on thermal and chemical stability, which could potentially be applied to other DUF3494 IBPs for future protein engineering.

Embracing firefly flash pattern variability with data-driven species classification.

Many nocturnally active fireflies use precisely timed bioluminescent patterns to identify mates, making them especially vulnerable to light pollution. As urbanization continues to brighten the night sky, firefly populations are under constant stress, and close to half of the species are now threatened. Ensuring the survival of firefly biodiversity depends on a large-scale conservation effort to monitor and protect thousands of populations. While species can be identified by their flash patterns, current methods require expert measurement and manual classification and are infeasible given the number and geographic distribution of fireflies. Here we present the application of a recurrent neural network (RNN) for accurate automated firefly flash pattern classification. Using recordings from commodity cameras, we can extract flash trajectories of individuals within a swarm and classify their species with an accuracy of approximately seventy percent. In addition to its potential in population monitoring, automated classification provides the means to study firefly behavior at the population level. We employ the classifier to measure and characterize the variability within and between swarms, unlocking a new dimension of their behavior. Our method is open source, and deployment in community science applications could revolutionize our ability to monitor and understand firefly populations.

An assessment of ten popular pregnancy applications (Apps) available for women in Australia.

OBJECTIVE: Given the growing popularity of health Apps, this study aimed to evaluate popular pregnancy Apps among Australian women. DESIGN: Ten popular pregnancy mobile device Apps accessible within Australia were assessed using the Deakin Health E-technologies Assessment Lab (HEAL) framework, the Australian Privacy Principles (APP) and other context-specific criteria. RESULTS: Most Apps were robust in use and user-friendly in terms of design. Based on the HEAL assessment, all the Apps scored between 70 and 89 out of 120. Only two of the ten Apps were locally hosted and operated. Only one App could search local health services using Victorian postcodes. All ten Apps were aligned with various privacy policy guidelines, but only one was reported to be fully aligned with the APP as it is locally hosted and operated. None of the Apps had accessibility features such as for visual or hearing difficulties. Only one App could be assessed as able to interface with the electronic medical record system in Australia due to a lack of publicly available information on this capability. CONCLUSIONS: Due to privacy concerns, pregnancy Apps accessible in Australia should be used with caution unless care is taken to select an App that fully complies with local requirements or international equivalents. All Apps were subjectively rated as moderate in quality, and more attention to accessibility and privacy features by App developers is recommended, along with the focus on integration with Australian digital health services.

Early offering transcatheter aortic valve replacement to patients with moderate aortic stenosis: quantifying costs and benefits - a Markov model-based simulation study.

OBJECTIVE: Aortic stenosis (AS) is one of the most common acquired cardiac valvular diseases. The success of transcatheter aortic valve implantation (TAVI) for severe AS has led to increasing interest in its use to earlier disease-moderate AS (MAS). DESIGN: Model-based study using a Markov microsimulation technique to evaluate the long-term costs and benefits associated with 'early' TAVI. Key data inputs were sourced from the international literature and costs were obtained from Australian sources. SETTING: Australian health care system perspective. PARTICIPANTS: 10 000 hypothetical MAS patients with or without left ventricular diastolic dysfunction or impaired left ventricular ejection fraction. INTERVENTION: Comparing early TAVI to medical management over a life time horizon for MAS patients aged >65 years. We evaluated the cost-effectiveness of offering early TAVI in five scenarios (10%, 25%, 50%, 75% and 90% take-up rates). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure is quality-adjusted life years (QALY) gained and the incremental cost-utility ratio (ICUR). Secondary outcomes are life-years gained and the number of heart failure case avoided. RESULTS: Offering early TAVI for MAS patients resulted in both higher healthcare costs and greater benefits (an increase of 3.02 QALYs or 3.99 life-years) per person treated. The ICUR was around $A10 867 and $A11 926 per QALY gained for all five scenarios, with the total cost of early TAVI to the healthcare system being anticipated to be up to $A3.66 billion. Sensitivity analyses indicated a 100% probability of being cost-effective with a willingness to pay threshold of $A50 000/QALY. The benefits remained, even with assumptions of high levels of repeat valve replacement after TAVI. CONCLUSION: While ongoing randomised controlled trials will define the benefit of TAVI to MAS patients, these results suggest that this intervention is likely to be cost-effective.

SOARinG to New Heights Through a Structured Medical Student Research Program.

Introduction: Since the US Medical Licensing Examination (USMLE) Step 1 became Pass/Fall in 2022, medical students competing for residency spots must distinguish themselves with alternative criteria. Research experiences and output offer valuable skill development and objective metrics to support competitive residency applications. Objective: We describe the methodological development of a structured program to support, enhance, and track medical student research efforts at the University of South Carolina School of Medicine Greenville, explain the implementation of the program, and summarize initial program outcomes. Methods: The Student Opportunities for Academic Achievement Through Research in Greenville (SOARinG) Program was established to serve as a centralized hub for rising second year medical student research. The program matched medical students with mentored research projects scheduled during the summer following first-year coursework. The program included a required weekly seminar series on research basics and current biomedical literature. SOARinG culminated with a student research symposium for which students submitted abstracts and presented a poster or a talk. Quantitative and qualitative program outcomes of student and mentor satisfaction with the program were measured through surveys. Results and Discussion: The program was successfully implemented in summers 2021 and 2022. Most students (80-95%) in each class engaged in mentored summer research projects. Students reported overall satisfaction with research projects and mentor support. Overall, 69% of students rated their overall research experience in the program as extremely good or very good. Each student submitted an abstract and presented at the program's symposium or alternate research venue. Overall, 97% of research mentors reported that students were adequately prepared for summer research and suggested that students would benefit from additional skills-specific research training. Conclusion: The SOARinG Program provided a formalized process for tracking and showcasing medical student research and allowed for increased student participation in research. Additionally, each participating student produced objective research output, thus enhancing future residency applications.

Obstetric Neuropathy in Diabetic Patients: The "Double Hit Hypothesis".

The two-hit model has been proposed to explain the effects of diabetes on mothers who are already in a putative subclinical damaged state and then undergo neuronal damage during the delivery process. However, the anatomical and pathophysiological mechanisms are not well understood. Our overarching hypothesis in this review paper is that pregnant women who are diabetic have a damaged peripheral nervous system, constituting the "first hit" hypothesis. The delivery process itself-the "second hit"-can produce neurological damage to the mother. Women with diabetes mellitus (DM) are at risk for neurological damage during both hits, but the cumulative effects of both "hits" pose a greater risk of neurological damage and pathophysiological changes during delivery. In our analysis, we introduce the different steps of our concept paper. Subsequently, we describe each of the topics. First, we outline the mechanisms by which diabetes acts as a detrimental variable in neuropathy by focusing on the most common form of diabetic neuropathy, diabetic distal symmetrical polyneuropathy, also known as distal sensorimotor neuropathy. The possible role of macrosomia in causing diabetic neuropathy and obstetric neurological injury is discussed. Second, we describe how vaginal delivery can cause various obstetrical neurological syndromes and pathophysiological changes. Third, we highlight the risk of obstetric neuropathy and discuss anatomical sites at which lesions may occur, including lesions during delivery. Fourth, we characterize the pathophysiological pathways involved in the causation of diabetic neuropathy. Finally, we highlight diabetic damage to sensory vs. motor nerves, including how hyperglycemia causes different types of damage depending on the location of nerve cell bodies.

Electrochemical interface based on polydopamine and gold nanoparticles/reduced graphene oxide for impedimetric detection of lung cancer cells.

The use of non-invasive approaches for monitoring therapy processes in cancer patients at late stages is truly needed. In this work, we aim to develop an electrochemical interface based on polydopamine combined with gold nanoparticles and reduced graphene oxide for impedimetric detection of lung cancer cells. Gold nanoparticles (around 75 nm) were dispersed onto reduced graphene oxide material pre-electrodeposited onto disposable fluorine doped tin oxide electrodes. The coordination between gold and carbonaceous material has somehow improved the mechanical stability of this electrochemical interface. Polydopamine was later introduced onto modified electrodes via self-polymerization of dopamine in an alkaline solution. The result has demonstrated the good adhesion and biocompatibility of polydopamine towards A-549 lung cancer cells. The presence of the two conductive materials (gold nanoparticles and reduced graphene oxide) has led to a six-times decrease in charge transfer resistance of polydopamine film. Finally, the as-prepared electrochemical interface was employed for impedimetric detection of A-549 cells. The detection limit was estimated to be only 2 cells per mL. These findings have proved the possibilities to use advanced electrochemical interfaces for point-of-care applications.

Unraveling cross-reactivity of anti-glycan IgG responses in filarial nematode infections.

Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode Brugia malayi and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing Brugia malayi glycans with plasma from uninfected individuals and from individuals infected with Loa loa, Onchocerca volvulus, Mansonella perstans and Wuchereria bancrofti, four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from Onchocerca volvulus and Mansonella perstans infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of Brugia malayi infected individuals. For these infection groups, Brugia malayi, Onchocerca volvulus and Mansonella perstans, we further studied the different IgG subclasses to Brugia malayi glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in Brugia malayi infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of Brugia malayi glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.

Mussel - Inspired biosorbent combined with graphene oxide for removal of organic pollutants from aqueous solutions.

In this work, we develop a mussel-inspired biosorbent combined with graphene oxide for removal of organic dyes in water sources. The composite was prepared via self-polymerization of dopamine in weak alkaline solution containing graphene oxide at ambient condition. Morphological and structural studies revealed that polydopamine has gradually grown to cover the surface of graphene oxide flakes, partially reduced these flakes, and somehow form many grains (size around 20 nm) on the flakes instead of making very large aggregates as usual. The mass ratio between two components of the composite was also investigated to find the optimal one which provides enough surface area (20 m2.g-1) and maintain adhesive sites in order to ensure high-efficiency removal of organic molecules. The adsorption kinetics and isotherms of as-prepared adsorbent towards methylene blue were found to fit well with pseudo-first order kinetics model and Langmuir isotherm. The maximum adsorption capacity (qm) and Langmuir constant (kL) were estimated to be 270 mg.g-1 and 0.49 L. mg-1. The as-prepared bio-sorbent is very promising for remediation of water sources contaminated with cationic organic molecules and heavy metal ions.

The incidence of pediatric ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Despite its importance in being among the top 10 causes of childhood death, there is limited data on the incidence of stroke in children and whether this has changed over time. AIMS: We performed a systematic review and meta-analysis to estimate the worldwide incidence rate of pediatric ischemic stroke, identify population differences, and assess trends in incidence. METHODS: We screened three databases (Medline, Embase, and Cumulative Index of Nursing and Allied Health Literature (CINAHL)) and a Google Search was performed up to October 2021. The protocol was pre-registered: PROSPERO: CRD42021273749. Data extraction and quality assessment were independently undertaken by two reviewers. A random-effects model was used for meta-analysis using Stata SE17 to calculate the overall incidence rate. Heterogeneity was assessed using I2. Meta-regression and assessment for bias were performed. RESULTS: Out of 4166 records identified, 39 studies were included in the qualitative synthesis and the quantitative meta-analysis. The incidence rate for all ischemic strokes varied from 0.9 to 7.9 per 100,000 person-years, with a pooled incidence of 2.09 (95% confidence interval (CI): 1.57-2.76). The pooled incidence was 1.28 (95% CI: 0.75-2.19) per 100,000 person-years for arterial ischemic stroke, and 0.56 (95% CI: 0.31-1.02) per 100,000 person-years for cerebral venous sinus thrombosis. The incidence of arterial ischemic stroke was high in neonates, less than 28 days old (18.51, 95% CI: 12.70-26.97). Significant heterogeneity was observed in the initial analyses of stroke incidence estimates, and geographical region, cohort age upper limit, length of study, study quality, and study design could not explain this. The incidence rate of childhood stroke appeared remained relatively stable over time. CONCLUSION: Our review provides estimates of global stroke incidence, including stroke subtypes, in children. It demonstrates a particularly high stroke incidence in neonates.

In vitro and in silico antioxidant and α-glucosidase inhibitory potential of compounds isolated from Garcinia gaudichaudii.

Nine compounds including a new one, garcichaudiic acid (1), were isolated from the bark of G. gaudichaudii and their structures were characterized mainly by 1 D and 2 D NMR experiments. The antioxidant capacity of the isolated compounds was determined using DPPH radical scavenging assay and the anti-hyperglycemic activity was assessed by measuring the inhibitory effect against α-glucosidase. Among them, compound 4 showed higher antioxidant activity than the positive control, ascorbic acid, while both compounds 1 and 7 exhibited more significant α-glucosidase inhibitory activity than the reference drug acarbose. Molecular docking analysis of the bioactive compounds was also performed to examine the binding modes and key interactions with the catalytic site.

Temporal Change in the Remaining Life Expectancy in People Who Underwent Percutaneous Coronary Intervention.

Whether percutaneous coronary intervention (PCI) is effective in improving long-term survival in an Australian PCI cohort remains unclear. We aimed to examine the change in the remaining life expectancy for patients who underwent PCI over the past decade. Patient data from the Melbourne Interventional Group were divided into four 3-year periods (2005 to 2007, 2008 to 2010, 2011 to 2013, and 2014 to 2016) for survival analysis. The primary outcome was time to death after PCI. Kaplan-Meier survival curves for overall survival were constructed to estimate the 5-year survival. To extrapolate the overall survival curve to the lifetime time horizon, 6 parametric survival distributions were fitted to the individual patient-level data against the Kaplan-Meier curve. The best fit distribution was selected based on goodness-of-fit statistics and expert opinion. The combination of annual mortality post-PCI from the parametric survival analysis and the background mortality by age informed the overall mortality rate. The life expectancy was compared with the general Australians. In addition, the utility weight of post-PCI patients was used to estimate the quality-adjusted life years gained. A total of 27,301 patients with a mean age of 64.4 ± 12 years were included. The base-case results showed that over the 4 time periods, the remaining life expectancy for patients aged 64.4 years on average at the time of PCI remained relatively stable except for period 4: 18.12 years (2005 to 2007), 17.56 years (2008 to 2010), 18.39 years (2011 to 2013), and 17.25 years (2014 to 2016), respectively. The quality-adjusted life years gained showed a similar trend: 14.86 (2005 to 2007), 14.40 (2008 to 2010), 15.07 (2011 to 2013), and 14.13 (2014 to 2016) separately. In conclusion, the widened gap in life expectancy in post-PCI patients versus the general Australian over the 2014 to 2016 period suggests the need for improved implementation of prevention strategies for coronary heart disease. Enhanced disease management after PCI that lowers residual mortality risk is recommended to extend the survival of patients with coronary heart disease.

Comparative structural insight into the unidirectional catalysis of ornithine carbamoyltransferases from Psychrobacter sp. PAMC 21119.

Ornithine carbamoyltransferases (OTCs) are involved in the arginine deiminase (ADI) pathway and in arginine biosynthesis. Two OTCs in a pair are named catalytic OTC (cOTC) and anabolic OTC (aOTC). The cOTC is responsible for catalyzing the third step of the ADI pathway to catabolize citrulline into carbamoyl phosphate (CP), as well as ornithine, and displays CP cooperativity. In contrast, aOTC catalyzes the biosynthesis of citrulline from CP and ornithine in vivo and is thus involved in arginine biosynthesis. Structural and biochemical analyses were employed to investigate the CP cooperativity and unidirectional function of two sequentially similar OTCs (32.4% identity) named Ps_cOTC and Ps_aOTC from Psychrobacter sp. PAMC 21119. Comparison of the trimeric structure of these two OTCs indicated that the 80s loop of Ps_cOTC has a unique conformation that may influence cooperativity by connecting the CP binding site and the center of the trimer. The corresponding 80s loop region of in Ps_aOTC was neither close to the CP binding site nor connected to the trimer center. In addition, results from the thermal shift assay indicate that each OTC prefers the substrate for the unidirectional process. The active site exhibited a blocked binding site for CP in the Ps_cOTC structure, whereas residues at the active site in Ps_aOTC established a binding site to facilitate CP binding. Our data provide novel insights into the unidirectional catalysis of OTCs and cooperativity, which are distinguishable features of two metabolically specialized proteins.

A systematic review of economic evaluations for the pharmaceutical treatment of chronic lymphocytic leukemia and acute myeloid leukemia.

INTRODUCTION: No recent full-text-based systematic review has been published to examine economic evidence around acute myeloid leukemia (AML) or chronic lymphocytic leukemia (CLL) treatment. We aimed to perform a systematic review in this area. AREAS COVERED: This review entailed searches in three main databases for economic evaluations of treatment in AML or CLL. After title and abstract screening, two reviewers examined all the citations in full text. Any disagreement between the two reviewers was resolved through discussion with the third reviewer. We used predesigned tools for data extraction, including study characteristics, primary results and conclusions. The quality of included studies was assessed. EXPERT OPINION: The majority of the studies adopted the modeling approach to estimate the long-term cost-effectiveness of the treatment from the healthcare system payer's perspective. Most studies concluded that the evaluated treatment interventions for untreated or refractory AML or CLL were cost-effective across various jurisdictions. The EQ-5D, followed by time trade-off and standard-gamble, was the most commonly used outcome measure to derive the utility weights associated with each health state. Clear justifications for the choice of modeling technique are recommended for future studies. Collecting the health-related quality of life outcome using a common instrument over the clinical trial could aid the comparability among economic studies.

Obesity and Bariatric Surgery in Australia: Future Projection of Supply and Demand, and Costs.

INTRODUCTION: The prevalence of obesity is increasing in developed countries, including Australia. There is evidence that bariatric surgery is effective in losing weight and reducing risk of chronic diseases. However, access to bariatric surgery remains limited in the public health sector. METHOD: We modelled population-based estimates of the likely numbers of people eligible for bariatric surgery in Australia using the recent Australian New Zealand Metabolic and Obesity Surgery Society (ANZMOSS) framework and estimated the potential costs that would be incurred from primary and subsequent reoperations in both public and private sector. RESULTS: The annual number of newly eligible patients is expected to rise, and hence the gap in demand is increasing relative to current baseline supply. If a 5-year program to treat all currently eligible patients was implemented, the maximum yearly demand is projected to be 341,343 primary surgeries, more than eight times the existing capacity of public and private sector, which can only offer 41,534 surgeries/year. A nine-fold increase is expected if we treat currently eligible patients over a 5-year program and all newly eligible patients as they occur each year. CONCLUSION: Our results highlighted the currently highly skewed distribution of bariatric surgeries between the private and public sectors. Improving access would bring substantial benefits to many Australians, given the demonstrated cost-effectiveness and cost savings. This requires a major increase in resourcing for publicly-funded access to bariatric surgery in the first instance. A national review of priorities and resourcing for all modes of obesity treatment is required in Australia.