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G-protein-coupled receptors (GPCRs) represent a ubiquitous membrane protein family and are important drug targets. Their diverse signaling pathways are driven by complex pharmacology arising from a conformational ensemble rarely captured by structural methods. Here, fluorine nuclear magnetic resonance spectroscopy (19F NMR) is used to delineate key functional states of the adenosine A2A receptor (A2AR) complexed with heterotrimeric G protein (Gαsß1γ2) in a phospholipid membrane milieu. Analysis of A2AR spectra as a function of ligand, G protein, and nucleotide identifies an ensemble represented by inactive states, a G-protein-bound activation intermediate, and distinct nucleotide-free states associated with either partial- or full-agonist-driven activation. The Gßγ subunit is found to be critical in facilitating ligand-dependent allosteric transmission, as shown by 19F NMR, biochemical, and computational studies. The results provide a mechanistic basis for understanding basal signaling, efficacy, precoupling, and allostery in GPCRs.
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Proteínas Heterotriméricas de Ligação ao GTP/química , Receptor A2A de Adenosina/química , Regulação Alostérica , Sítios de Ligação , Proteínas Heterotriméricas de Ligação ao GTP/genética , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Humanos , Cinética , Ligantes , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Nanoestruturas/química , Ligação Proteica , Conformação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Receptor A2A de Adenosina/genética , Receptor A2A de Adenosina/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Transdução de SinaisRESUMO
BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).
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Antibacterianos , Antibioticoprofilaxia , Artroplastia de Substituição , Cefazolina , Infecção da Ferida Cirúrgica , Vancomicina , Adulto , Humanos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/efeitos adversos , Antibioticoprofilaxia/métodos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Austrália , Cefazolina/efeitos adversos , Cefazolina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Vancomicina/efeitos adversos , Vancomicina/uso terapêutico , Método Duplo-Cego , Artroplastia de Substituição/efeitos adversos , Artroplastia de Substituição/métodos , Artroplastia de Substituição/estatística & dados numéricosRESUMO
The adenosine A2A receptor (A2AR) engages several G proteins, notably Go and its cognate Gs protein. This coupling promiscuity is facilitated by a dynamic ensemble, revealed by 19F nuclear magnetic resonance imaging of A2AR and G protein. Two transmembrane helix 6 (TM6) activation states, formerly associated with partial and full agonism, accommodate the differing volumes of Gs and Go. While nucleotide depletion biases TM7 toward a fully active state in A2AR-Gs, A2AR-Go is characterized by a dynamic inactive/intermediate fraction. Molecular dynamics simulations reveal that the NPxxY motif, a highly conserved switch, establishes a unique configuration in the A2AR-Go complex, failing to stabilize the helix-8 interface with Gs, and adoption of the active state. The resulting TM7 dynamics hamper G protein coupling, suggesting kinetic gating may be responsible for reduced efficacy in the noncognate G protein complex. Thus, dual TM6 activation states enable greater diversity of coupling partners while TM7 dynamics dictate coupling efficacy.
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Mucins are large, highly glycosylated transmembrane and secreted proteins that line and protect epithelial surfaces. However, the details of mucin biosynthesis and packaging in vivo are largely unknown. Here, we demonstrate that multiple distinct mucins undergo intragranular restructuring during secretory granule maturation in vivo, forming unique structures that are spatially segregated within the same granule. We further identify temporally-regulated genes that influence mucin restructuring, including those controlling pH (Vha16-1), Ca2+ ions (fwe) and Cl- ions (Clic and ClC-c). Finally, we show that altered mucin glycosylation influences the dimensions of these structures, thereby affecting secretory granule morphology. This study elucidates key steps and factors involved in intragranular, rather than intergranular segregation of mucins through regulated restructuring events during secretory granule maturation. Understanding how multiple distinct mucins are efficiently packaged into and secreted from secretory granules may provide insight into diseases resulting from defects in mucin secretion.
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Mucinas , Vesículas Secretórias , Grânulos Citoplasmáticos/metabolismo , Glicosilação , Mucinas/metabolismo , Vesículas Secretórias/metabolismoRESUMO
Futuristic wearable electronics desperately need power sources with similar flexibility and durability. In this regard, the authors, therefore, propose a scalable PAN-PMMA blend-derived electrospinning protocol to fabricate free-standing electrodes comprised of cobalt hexacyanoferrate nanocube cathode and tin metal organic framework-derived nanosphere anode, respectively, for flexible sodium-ion batteries. The resulting unique inter-networked nanofiber mesh offers several advantages such as robust structural stability towards repeated bending and twisting stresses along with appreciable electronic/ionic conductivity retention without any additional post-synthesis processing. The fabricated flexible sodium ion full cells deliver a high working voltage of 3.0 V, an energy density of 273 Wh·kg-1 , and a power density of 2.36 kW·kg-1 . The full cells retain up to 86.73% of the initial capacity after 1000 cycles at a 1.0 C rate. After intensive flexibility tests, the full cells also retain 78.26% and 90.78% of the initial capacity after 1000 bending and twisting cycles (5 mm radius bending and 40o axial twisting), respectively. This work proves that the proposed approach can also be employed to construct similar robust, free-standing nanofiber mesh-based electrodes for mass-producible, ultra-flexible, and durable sodium ion full cells with commercial viability.
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This research designs a triphasic Ni2P-Ni12P5-Ru heterostructure with amorphous interface engineering strongly coupled by a cobalt nano-surface (Co@NimPn-Ru) to form a hierarchical 3D interconnected architecture. The Co@NimPn-Ru material promotes unique reactivities toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media. The material delivers an overpotential of 30 mV for HER at 10 mA cm-2 and 320 mV for OER at 50 mA cm-2 in freshwater. The electrolyzer cell derived from Co@NimPn-Ru(+,-) requires a small cell voltage of only 1.43 V in alkaline freshwater or 1.44 V in natural seawater to produce 10 mA cm-2 at a working temperature of 80 °C, along with high performance retention after 76 h. The solar energy-powered electrolyzer system also shows a prospective solar-to-hydrogen conversion efficiency and sufficient durability, confirming its good potential for economic and sustainable hydrogen production. The results are ascribed to the synergistic effects by an exclusive combination of multi-phasic crystalline Ni2P, Ni12P5, and Ru clusters in presence of amorphous phosphate interface attached onto cobalt nano-surface, thereby producing rich exposed active sites with optimized free energy and multi open channels for rapid charge transfer and ion diffusion to promote the reaction kinetics.
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The high theoretical energy density (2600 Wh kg-1) and low cost of lithium-sulfur batteries (LSBs) make them an ideal alternative for the next-generation energy storage system. Nevertheless, severe capacity degradation and low sulfur utilization resulting from shuttle effect hinder their commercialization. Herein, Single-atom Ru-doped 1T/2H MoS2 with enriched defects decorates V2C MXene (Ru-MoS2/MXene) produced by a new phase-engineering strategy employed as sulfur host to promote polysulfide adsorption and conversion reaction kinetics. The Ru single atom-doped adjusts the chemical environment of the MoS2/MXene to anchor polysulfide and acts as an efficient center to motivate the redox reaction. In addition, the rich defects of the MoS2 and ternary boundary among 1T/2H MoS2 and V2C accelerate the charge transfer and ion movements for the reaction. As expected, the Ru-MoS2/MXene/S cathode-based cell exhibits a high-rate capability of 684.3 mAh g-1 at 6 C. After 1000 cycles, the Ru-MoS2/MXene/S cell maintains an excellent cycling stability of 696 mAh g-1 at 2 C with a capacity degradation as low as 0.02% per cycle. Despite a high sulfur loading of 9.5 mg cm-2 and a lean electrolyte-to-sulfur ratio of 4.3, the cell achieves a high discharge capacity of 726 mAh g-1.
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OBJECTIVES: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste. DESIGN: Prospective, randomized, parallel group, noninferiority clinical trial. SETTING: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022. PATIENTS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L. INTERVENTIONS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program. MEASUREMENT AND MAIN RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents). CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.
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Estado Terminal , Hipofosfatemia , Fosfatos , Humanos , Hipofosfatemia/economia , Masculino , Feminino , Pessoa de Meia-Idade , Estado Terminal/terapia , Estado Terminal/economia , Fosfatos/sangue , Estudos Prospectivos , Idoso , Nutrição Enteral/economia , Nutrição Enteral/métodos , Hidratação/métodos , Hidratação/economia , Adulto , Custos de Cuidados de Saúde/estatística & dados numéricos , Unidades de Terapia IntensivaRESUMO
AIM: Incorporating health-related quality of life (HRQoL) measures into health economic analyses can help to provide evidence to inform decisions about how to improve patient outcomes in the most cost-effective manner. The aim of this narrative review was to assess which HRQoL instruments have been used in economic evaluations of type 2 diabetes management including in Indigenous communities. METHOD: MEDLINE (Ovid), Embase (Ovid) and Cochrane were searched from inception to June 2022. Studies included patients with type 2 diabetes; economic evaluations, derived scores from direct questioning of individuals; and were in English. Records were assessed for bias using the JBI critical appraisal tools. RESULTS: A total of 3737 records were identified, with 22 publications meeting the criteria for inclusion. Across those 22 articles, nine HRQoL instruments had been utilised. Generic tools were most frequently used to measure HRQoL, including EQ-5D (-3 L and -5 L) (n = 10, 38%); SF-12 (n = 5, 19%); and SF-36 (n = 4, 15%). Two tools addressing the specific stressors faced by people with type 2 diabetes were utilised: Problem Areas In Diabetes tool (n = 1, 4%) and Diabetes Distress Scale (n = 1, 4%). Two publications reported whether the study population included Indigenous peoples. CONCLUSION: A wide range of HRQoL instruments are used in economic evaluations of type 2 diabetes management, with the most frequent being varying forms of the EQ-5D. Few economic evaluations noted whether Indigenous peoples were featured in the study population. More research into HRQoL in people living with type 2 diabetes is urgently needed to improve evidence on effectiveness and cost-effectiveness of interventions.
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OBJECTIVES: The Mount Hood Diabetes Challenge Network aimed to examine the impact of model structural uncertainty on the estimated cost-effectiveness of interventions for type 2 diabetes. METHODS: Ten independent modeling groups completed a blinded simulation exercise to estimate the cost-effectiveness of 3 interventions in 2 type 2 diabetes populations. Modeling groups were provided with a common baseline population, cost and utility values associated with different model health states, and instructions regarding time horizon and discounting. We collated the results to identify variation in predictions of net monetary benefit (NMB) and the drivers of those differences. RESULTS: Overall, modeling groups agreed which interventions had a positive NMB (ie, were cost-effective), Although estimates of NMB varied substantially-by up to £23 696 for 1 intervention. Variation was mainly driven through differences in risk equations for complications of diabetes and their implementation between models. The number of modeled health states was also a significant predictor of NMB. CONCLUSIONS: This exercise demonstrates that structural uncertainty between different health economic models affects cost-effectiveness estimates. Although it is reassuring that a decision maker would likely reach similar conclusions on which interventions were cost-effective using most models, the range in numerical estimates generated across different models would nevertheless be important for price-setting negotiations with intervention developers. Minimizing the impact of structural uncertainty on healthcare decision making therefore remains an important priority. Model registries, which record and compare the impact of structural assumptions, offer one potential avenue to improve confidence in the robustness of health economic modeling.
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Perilipins are evolutionarily conserved from insects to mammals. Drosophila lipid storage droplet-1 (LSD-1) is a lipid storage droplet membrane surface-binding protein family member and a counterpart to mammalian perilipin 1 and is known to play a role in lipolysis. However, the function of LSD-1 during specific tissue development remains under investigation. This study demonstrated the role of LSD-1 in salivary gland development. Knockdown of Lsd-1 in the salivary gland was established using the GAL4/UAS system. The third-instar larvae of knockdown flies had small salivary glands containing cells with smaller nuclei. The null mutant Drosophila also showed the same phenotype. The depletion of LSD-1 expression induced a delay of endoreplication due to decreasing CycE expression and increasing DNA damage. Lsd-1 genetically interacted with Myc in the third-instar larvae. These results demonstrate that LSD-1 is involved in cell cycle and cell death programs in the salivary gland, providing novel insight into the effects of LSD-1 in regulating salivary gland development and the interaction between LSD-1 and Myc.
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Morte Celular , Proteínas de Drosophila , Larva , Glândulas Salivares , Animais , Glândulas Salivares/metabolismo , Glândulas Salivares/citologia , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Larva/genética , Drosophila/metabolismo , Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Replicação do DNA , Proteínas de Ligação a DNA , Oxirredutases N-Desmetilantes , Fatores de TranscriçãoRESUMO
This study introduces an innovative approach using highly efficient nanocomposite materials to effectively remove PFAS from water, demonstrating remarkable adsorption capabilities. The nanocomposite was synthesized by integrating a zirconium-based metal-organic framework (MOF) called UiO-66 with graphene oxide (GO) within a polyvinyl alcohol (PVA) matrix. The resulting PVA@UiO-66/GO material features flower-like UiO-66 MOF crystals embedded in the PVA and GO matrix. Various kinetic models were applied to determine the rate constants and adsorption capacities, with the Langmuir isotherm indicating an adsorption capacity of 9.904 mg/g. Thermodynamic analysis confirmed the process's spontaneity and exothermic nature. The UiO-66-NH2/GO/PVA composite also demonstrated high reusability, maintaining substantial PFOA removal efficiency across multiple cycles, with optimal reduction occurring at approximately pH 5. Overall, the PVA@UiO-66/GO composites offer an effective, sustainable, and environmentally friendly solution for PFAS removal in water purification.
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Background and Objectives: Hip fractures in the elderly pose a considerable health risk and cause concern. Red blood cell distribution width (RDW) is a valuable marker for identifying patients at high risk of age-related mortality and various disorders and diseases. However, its association with poor patient outcomes following hip fractures has yet to be fully established. Hence, the purpose of this meta-analysis was to investigate and gain a better understanding of the relationship between RDW levels and the risk of mortality after hip fractures. Materials and Methods: PubMed, Embase, Web of Science, and other databases were comprehensively searched until April 2023 to identify relevant studies. The meta-analysis included observational studies finding the association between RDW at admission or preoperation and short-term and long-term mortality rates following hip fractures. The results were presented in terms of odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: This meta-analysis included 10 studies involving 5834 patients with hip fractures. Patients with preoperative RDW of over 14.5% had higher risks of 1-year (OR: 5.40, 95% CI: 1.89-15.48, p = 0.002) and 3-month (OR: 2.91, 95% CI: 1.42-5.95, p = 0.004) mortality. Higher admission or preoperative RDW was significantly associated with an 11% higher mortality risk after 1 year (HR: 1.11, 95% CI: 1.06-1.17, p < 0.00001). Patients with higher preoperative RDW had a significantly higher risk of 6-month mortality, which was three times that of those with lower preoperative RDW (OR: 3.00, 95% CI: 1.60-5.61, p = 0.0006). Higher preoperative RDW was correlated to a higher 30-day mortality risk (OR: 6.44, 95% CI: 3.32-12.47, p < 0.00001). Conclusions: Greater RDW values at admission or before surgery were associated with a higher risk of short-term and long-term mortality following hip fractures. Because RDW can be easily measured using a routine blood test at a low cost, this parameter is promising as an indicator of mortality in elderly patients with hip fractures.
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Fraturas do Quadril , Humanos , Idoso , Hospitalização , Índices de Eritrócitos , Eritrócitos , PrognósticoRESUMO
BACKGROUND: Smoking has long been recognized as a risk factor for impaired wound and bone healing, particularly in the context of ankle and foot surgery. Despite numerous studies exploring the association between smoking and complications following ankle replacement, there remains significant inconsistency in their findings. Therefore, this meta-analysis study aims to elucidate whether smoking increases the rate of complications after total ankle arthroplasty (TAA), providing valuable insights for clinical management. METHODS: A comprehensive systematic search was conducted in the PubMed, Embase, and Wiley databases to identify relevant English studies on the influence of smoking on postoperative complications following ankle replacement without any restrictions on publication dates. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Random-effect models were used to calculate odds ratios (OR) and 95 % confidence intervals (CI). This study adhered to PRISMA guidelines for transparent reporting and was registered with PROSPERO. RESULTS: The analysis incorporated data from 12 retrospective cohort studies, totaling 17331 subjects, 2580 of whom were smokers and 791 complications following TAA. The findings revealed a statistically significant disparity in wound-related complications (OR: 2.26; 95 % CI: 1.13-4.50; P = .02), particularly evident in current smokers with an OR of 3.30 (95 % CI: 2.12-5.14; P < .00001). However, we lacked sufficient evidence to substantiate an association between smoking and complications related to the prosthesis (OR: 1.09; 95 % CI: 0.77-1.53; P = .64) or systemic complications (OR: 1.18; 95 % CI: 0.10-14.13; P = .90) following TAA. CONCLUSIONS: Smoking, especially current smoking, is associated with increased wound complication risk post-operation for total ankle arthroplasty. Despite a lack of definitive evidence on the optimal timeframe for smoking cessation before surgery, discontinuing smoking appears to be a prudent measure to mitigate these complications.
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PURPOSE: We conducted a systematic review of studies reporting on measurement of health-related quality of life (HRQoL), with a special focus on the use of the preference-weighted instruments, in patients with extremity bone sarcoma treated with limb-salvage surgery or amputation. METHODS: We searched MedLine, Embase, Cochrane Library and Web of Science for English-language studies reporting on HRQoL of patients with bone sarcoma from inception to 28 August 2023. All records found were independently reviewed by two reviewers. We used the Newcastle-Ottawa Scale (NOS) and the CONSORT 2010 checklist to assess the quality of the cohort and randomised studies, respectively. RESULTS: The search identified 1225 records, of which 16 studies were included for data extraction. Only one study used a preference-weighted instrument for measuring HRQoL in a small sample of patients (n = 28). Ten studies used the generic SF-36 questionnaire, but no preference-weighted HRQoL based on SF-6D was derived from the SF-36 scores. Most studies comparing HRQoL between amputation and limb-salvage surgery reported no significant differences. Twelve cohort studies scored six or more out of nine points based on the NOS. The only randomised study scored 54% on the CONSORT 2010 checklist. CONCLUSIONS: The approaches used to measure HRQoL were inconsistent and outcome scores varied substantially. Only one study used preference-weighted instruments for HRQoL measurement. Future research into the surgical treatment of extremity bone sarcoma should consider the use of preference-weighted instruments to measure HRQoL, which will therefore enable economic evaluation for the growing orthopaedic armamentarium of novel surgical interventions. REGISTRATION: This systematic review was registered with the PROSPERO International prospective register of systematic reviews (CRD42021282380).
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PURPOSE: Many generic patient-reported instruments are available for the measurement of health outcomes, including EQ-5D-5L, and the Patient-Reported Outcome Measurement Information System (PROMIS). Assessing their measurement characteristics informs users about the consistency between, and limits of, evidence produced. The aim was to assess the measurement relationship between the EQ-5D-5L descriptive system and value sets, the PROMIS-29 and PROPr (PROMIS value set). METHODS: Data were extracted from a cross-sectional survey administering measures of quality of life online in Australia. Descriptive analysis, agreement and construct validity assessment methods were used to compare instruments at the item, domain and value set level. RESULTS: In total, 794 Australians completed the survey. Convergent validity analysis found that similar dimensions across instruments were highly correlated (> 0.50), but the PROMIS-29 assesses additional health concepts not explicitly covered by EQ-5D (sleep and fatigue). Known-group assessment found that EQ-5D-5L and PROPr were able to detect those with and without a condition (ES range 0.78-0.83) but PROPr could more precisely detect differing levels of self-reported health. Both instruments were sensitive to differences in levels of pain. DISCUSSION: There is some consistency in what the EQ-5D-5L, PROMIS-29 and PROPr measure. Differences between value set characteristics can be linked to differences what is measured and the valuation approaches used. This has implications for the use of each in assessing health outcomes, and the results can inform decisions about which instrument should be used in which context.
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Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Estudos Transversais , Psicometria/métodos , Austrália , Inquéritos e Questionários , Reprodutibilidade dos Testes , Nível de SaúdeRESUMO
This cost analysis, from a societal perspective, compared the cost difference of a networked teletrial model (NTTM) with four regional hubs versus conventional trial operation at a single metropolitan specialist centre. The Australian phase 3 cancer interventional randomised controlled trial included 152 of 328 regional participants (patient enrolment 2018-2021; 6-month primary end point). The NTTM significantly reduced (AU$2155 per patient) patient travel cost and time and lost productivity.
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Neoplasias , Telemedicina , Humanos , Austrália/epidemiologia , Análise Custo-Benefício , Custos e Análise de Custo , Oncologia , Neoplasias/epidemiologia , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
PURPOSE: Orthognathic surgery (OGS) using the surgery-first approach (SFA) can decrease treatment time and increase patient satisfaction. Clockwise rotation (CWR) of the maxillomandibular complex to correct mandibular prognathism leads to optimized functional, aesthetic, and stable outcomes. This study examined the combined effect of SFA and CWR of the maxillomandibular complex to correct mandibular prognathism by comparing the surgical movement before (T0) and immediately after OGS (T1) and the stability between T1 and 12 months after OGS (T2). METHODS: This prospective cohort study enrolled patients with skeletal Class III malocclusion who underwent SFA involving Le Fort I osteotomy and bilateral sagittal split osteotomy, with or without genioplasty. Based on the occlusal plane (OP) change at T0-T1, the patients were divided into CWR (OP > 4°) and control (C) groups (OP ≤ 4°). The predictor variable was OP change at T0-T1. The primary outcome variable was the stability of pogonion (Pog) at T1-T2. The covariates included demographic factors, cephalometric measurements (anterior facial height, posterior facial height, OP, mandibular plane angle, incisor mandibular plane angle, overjet, and overbite), and 3-dimensional landmark displacement (anterior nasal spine, A-point, upper central incisor, upper first molar, lower central incisor, lower first molar, Pog, gonion, and condylion). An independent t-test was used to compare between these 2 groups when appropriate. The level of significance was set at P < .05. RESULTS: The sample included 28 patients (17 females) in the C group and 36 (24 females) in the CWR group; the mean ages were 23.89 ± 3.35 and 24.08 ± 4.02 years, respectively. For the surgical movement at T0-T1, the CWR group showed an association with vertical movement of the maxilla at posterior nasal spine (P = .005), anterior nasal spine (P < .001), and A-point (P < .001) and horizontal backward movement of the mandible at B-point (P < .001), Pog (P < .001), and gonion (P = .042). At T1-T2, all landmarks remained stable without clinically significant difference between the 2 groups. CONCLUSION: Surgical movement in the CWR group could vertically displace the maxilla and setback mandible more than that in the C group. Postoperative skeletal stability remained the same between the 2 groups at 1 year after OGS.
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Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Prognatismo , Feminino , Humanos , Adulto Jovem , Adulto , Prognatismo/cirurgia , Estudos Prospectivos , Rotação , Seguimentos , Procedimentos Cirúrgicos Ortognáticos/métodos , Osteotomia de Le Fort/métodos , Osso Nasal , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Maxila/cirurgia , Cefalometria/métodosRESUMO
BACKGROUND: Facial aesthetics may be optimized based on a deeper understanding of soft tissue changes after orthognathic surgery. PURPOSE: The purpose of the study was to delineate facial soft tissue changes after clockwise rotation (CWR) of the maxillomandibular complex (MMC) to correct mandibular prognathism using the surgery-first approach. STUDY DESIGN, SETTING, SAMPLE: This prospective cohort study enrolled patients over 18 years of age with skeletal Class III malocclusion in the craniofacial center. The patients were excluded with previous history of craniofacial syndrome, orthognathic surgery trauma, infection at surgical sites, chin deviation (menton deviation ≥4 mm), 2 or more missing data points after surgery, or without informed consent. This study compared significant facial changes before (T0) and after orthodontic debonding (T1) in the CWR and control groups. PREDICTOR VARIABLE: The patients were divided in accordance with maxillary occlusal plane change (OPC) after surgery into CWR (OPC >4°) and control (OPC ≤4°) groups. MAIN OUTCOME VARIABLE: The primary outcome variable was frontal lip curvature (FLC: Right Cheilion-Stomion-Left Cheilion, degree) with or without upper lip curving upward at T1, where upper lip curving upward was considered more favorable. COVARIATES: The covariates included age, sex, and various cephalometric measurements. ANALYSES: The Mann-Whitney U test, paired, and independent t-test were implemented to compare the intragroup and intergroup differences. Statistical significance was indicated by P value <.05. RESULTS: The study comprised 34 patients (21 women) in the control group and 37 (29 women) in the CWR group; their mean ages were 23.64 ± 4.38 and 24.21 ± 3.84 years, respectively (P value = .562). At T1, the CWR group had significant increased FLC (P value = .001), alar width (P value = .034), and lower vermilion height (P value = .018), and decreased lower lip length (P value = .004). The high FLC group had significant decreased upper lip projection (P value = .002) and increased nasolabial angle (P value = .013). The significant relationship between CWR and high FLC was supported by the χ2 test (P value = .018) and multiple logistic regression (P value = .017). CONCLUSION: Greater CWR of the MMC increased FLC and lower vermilion height and reduced lower lip length. High FLC resulting from the CWR of the MMC improved facial appearance by moving the upper lip curve upward.
Assuntos
Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Prognatismo , Humanos , Feminino , Adolescente , Adulto , Adulto Jovem , Prognatismo/cirurgia , Estudos Prospectivos , Rotação , Procedimentos Cirúrgicos Ortognáticos/métodos , Má Oclusão Classe III de Angle/cirurgia , Lábio , Maxila/diagnóstico por imagem , Maxila/cirurgia , Cefalometria/métodos , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgiaRESUMO
Continued advances in label-free electrical biosensors pave the way to simple, rapid, cost-effective, high-sensitivity, and quantitative biomarker testing at the point-of-care setting that would profoundly transform healthcare. However, implementation in routine diagnostics is faced with significant challenges associated with the inherent requirement for biofluid sample processing before and during testing. We present here a simple yet robust autonomous finger-prick blood sample processing platform integrated with nanoscale field-effect transistor biosensors and demonstrate the feasibility of measuring the SARS-CoV-2 nucleocapsid protein. The 3D-printed platform incorporates a high-yield blood-to-plasma separation module and a delay valve designed to terminate the assay at a specific time. The platform is driven by hydrostatic pressure to efficiently and automatically dispense plasma and washing/measurement buffer to the nanosensors. Our model study demonstrates the feasibility of detecting down to 1.4 pg/mL of the SARS-CoV-2 nucleocapsid protein within 25 min and with only minimal operator intervention.