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1.
JDS Commun ; 4(5): 349-353, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37727235

RESUMO

There has been limited research on the recent increase in US anaerobic dairy digesters. We use panel data to estimate a double hurdle model that predicts both the probability that a county has a dairy digester and the number of digesters in counties that have them. Dairy farms and retail electricity prices affect dairy digesters, although the parameter estimates are inelastic. Biogas-producing landfills, which reflect policies and infrastructure that enable renewable energy, also affect digesters. Our findings on the conditions that are conducive to dairy digesters will help policymakers consider options for reducing manure methane emissions.

2.
J Dairy Sci ; 106(8): 5474-5484, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37291037

RESUMO

The greenhouse gas emission intensity of US milk production (i.e., greenhouse gas emissions per unit of production) has varied across time and states. However, research has not examined how farm-sector trends affect the state-level emission intensity of production. We estimated fixed effects regressions with state-level panel data from 1992 through 2017 to test how US dairy farm-sector changes influenced the greenhouse gas emission intensity of production. We found that increases in per cow milk productivity reduced the enteric greenhouse gas emission intensity of milk production, while it had no statistically significant effect on the manure greenhouse gas emission intensity of production. In contrast, increases in average farm size and the number of farms reduced the manure greenhouse gas emission intensity of milk production, while they did not affect the enteric greenhouse gas emission intensity of production.


Assuntos
Gases de Efeito Estufa , Bovinos , Feminino , Animais , Gases de Efeito Estufa/análise , Leite/química , Efeito Estufa , Esterco/análise , Indústria de Laticínios , Metano
3.
J Immunol Methods ; 518: 113492, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37201783

RESUMO

BACKGROUND: Detecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. METHODS: We compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. RESULTS: Baseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. CONCLUSIONS: This is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.


Assuntos
COVID-19 , Humanos , Adulto Jovem , COVID-19/diagnóstico , SARS-CoV-2 , Anticorpos Antivirais , Teste em Amostras de Sangue Seco , Imunoglobulina G , Imunoglobulina A , Imunoglobulina M , Sensibilidade e Especificidade
4.
Sci Justice ; 62(5): 644-656, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36336458

RESUMO

The surface structure of mint (as-issued) and handled polymer five pounds sterling banknotes was studied by atomic force microscopy and laser scanning confocal microscopy. A total of 1856 fingermarks on mint and handled banknotes from four different issuing banks (Bank of England, Bank of Scotland, Royal Bank of Scotland and Clydesdale Bank) were visualised with Vacuum Metal Deposition (VMD), Cyanoacrylate Fuming (CAF) and, on Clydesdale Bank notes, magnetic fluorescent powder. VMD was significantly more effective in developing fingermarks on handled banknotes, across all the banks studied, although effectiveness varied with issuing bank. For example, on handled Bank of England notes 45% of marks showed ridge detail with VMD development and 28% with CAF; for Bank of Scotland handled notes success rates were 17% with VMD and 1% with CAF. Microscopy of degraded banknotes showed the loss of intaglio printing and the formation of a cracked surface structure in the handled notes. These features can lead to the trapping of powder, or contaminants, increasing quantity of development agent in fingermark background between the ridges, decreasing contrast and decreasing performance of powder-based fingermark development techniques. These same features can restrict the migration of components of the fingermark, preventing fingermarks degrading through spread of material and thus reducing potential formation of empty prints, so that VMD development is not adversely affected.


Assuntos
Dermatoglifia , Polímeros , Humanos , Pós , Cianoacrilatos/química , Vácuo , Metais
5.
Front Mol Biosci ; 8: 778244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926581

RESUMO

It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights.

7.
AJNR Am J Neuroradiol ; 42(10): 1798-1806, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34385142

RESUMO

BACKGROUND AND PURPOSE: Delays to reperfusion negatively impact outcomes of patients with ischemic stroke, yet current guidelines recommend selective sequential imaging for thrombectomy candidates. We aimed to quantify and analyze time delays associated with rescanning in sequential acute stroke imaging. MATERIALS AND METHODS: This was a retrospective cohort study of consecutive patients with acute ischemic stroke who underwent imaging for treatment decision-making from January 1, 2017, to June 30, 2020. Rescan time delay was defined as ≥10-minute difference between initial NCCT and CTA ± CTP. Mean rescan time delays in comprehensive and primary stroke centers were compared. Bivariate and multivariable regression analyses assessed clinical and imaging factors associated with rescanning time delays and early outcomes. RESULTS: A total of 588 patients with acute ischemic were included in statistical analyses. Rescanning occurred in 27.9% (164/588 patients), with a mean time delay of 53.7 (SD, 43.4) minutes. For patients presenting at primary compared with comprehensive stroke centers, rescan time delays were more common (59.6% versus 11.8%, P < .001), with longer delays (65.4 [SD, 45.4] minutes versus 23.6 [SD, 14.0] minutes, P < .001). Independent predictors of rescan time delays included primary stroke center presentation, intravenous thrombolysis administration, black race, admission NIHSS ≥10, baseline independent ambulation, and onset-to-comprehensive stroke center arrival in ≥6 hours. Protocols for early simultaneous comprehensive CT (NCCT + CTA + CTP) were associated with lower odds of time delays (OR = 0.34; 95% CI, 0.21-0.55). Rescanning was associated with lower odds of home discharge (OR = 0.53; 95% CI, 0.30-0.95). CONCLUSIONS: A sequential approach to CT-based imaging may be significantly associated with prolonged acute stroke evaluations. Adoption of early simultaneous comprehensive CT could minimize treatment delays and improve outcomes.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Trombectomia , Resultado do Tratamento
8.
Eur J Appl Physiol ; 121(5): 1451-1459, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33629149

RESUMO

PURPOSE: Heat stress exacerbates post-exercise hypotension (PEH) and cardiovascular disturbances from elevated body temperature may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are possible modifiers, though these hypotheses lack practical evidence. This study had three aims: (1) to characterise pre-post-responses in histamine and mast cell tryptase (MCT), (2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post-marathon, (3) to identify any differences in incapacitated runners. METHODS: 24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured at baseline. A further eight participants were recruited from incapacitated runners (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon incapacitation (COLLAPSE). RESULTS: In completion, MCT increased by nearly 50% from baseline (p = 0.0049), whereas histamine and body temperature did not vary (p > 0.946). Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p < 0.019). WBMM negatively correlated with Δ SBP (r = - 0.43, p = 0.046). For collapse versus completion, there were significant elevations in MCT (1.77 ± 0.25 µg/L vs 1.18 ± 0.43 µg/L, p = 0.001) and body temperature (39.8 ± 1.3 °C vs 36.2 ± 0.8 °C, p < 0.0001) with a non-significant rise in histamine (9.6 ± 17.9 µg/L vs 13.7 ± 33.9 µg/L, p = 0.107) and significantly lower MAP, DBP and SVR (p < 0.033). CONCLUSION: These data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.


Assuntos
Histamina/metabolismo , Corrida de Maratona , Mastócitos/enzimologia , Hipotensão Pós-Exercício/diagnóstico por imagem , Hipotensão Pós-Exercício/metabolismo , Triptases/metabolismo , Adulto , Biomarcadores , Determinação da Pressão Arterial , Composição Corporal , Temperatura Corporal , Estudos de Casos e Controles , Ecocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Estudos Prospectivos
9.
J Prev Alzheimers Dis ; 8(2): 123-126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33569557

RESUMO

BACKGROUND: Recent Alzheimer's disease (AD) trials have faced significant challenges to enroll pre-symptomatic or early stage AD subjects with biomarker positivity, minimal or no cognitive impairment, and likelihood to decline cognitively during a short trial period. Our previous study showed that digital cognitive biomarkers (DCB), generated by a hierarchical Bayesian cognitive process (HBCP) model, were able to distinguish groups of cognitively normal individuals with impending cognitive decline from those without. We generated DCBs using only baseline Auditory Verbal Learning Test's wordlist memory (WLM) item response data from the Mayo Clinic Alzheimer's Disease Patient Registry. OBJECTIVES: To replicate our previous findings, using baseline ADAS-Cog WLM item response data from the Alzheimer's Disease Neuroimaging Initiative, and compare DCBs to traditional approaches for scoring word-list memory tests. DESIGN: Classified decliner subjects (n = 61) as those who developed amnestic MCI or AD dementia within 3 years of normal baseline assessment and non-decliner (n = 442) as those who did not. MEASURES: Evaluated the relative value of DCBs compared to traditional measures, using three analytic approaches to group differences: 1) logistic regression of summary scores per ADAS-Cog WLM task; 2) Bayesian modeling of summary scores; and 3) HBCP modeling to generate DCBs from item-level responses. RESULTS: The HBCP model produced posterior distributions of group differences, of which Bayes factor assessment identified three DCBs with notable group differences: Immediate Retrieval from Durable Storage, (BFds = 11.8, strong evidence); One-Shot Learning, (BFds = 4.5, moderate evidence); and Partial Learning (BFds = 2.9, weak evidence). In contrast, logistic regression of summary scores did not significantly discriminate between groups, and the Bayes factor assessment of modeled summary scores provided moderate evidence that the groups were equivalent (BFsd = 3.4, 3.1, 2.9, and 1.4, respectively). CONCLUSIONS: This study demonstrated DCBs' ability to distinguish , at baseline, between impending cognitive decline and non-decline groups where individuals in both groups were classified as cognitively normal. This validated findings from our previous study, demonstrating DCBs' advantages over traditional approaches. This study warrants further refinement of the HBCP DCBs to predict impending cognitive decline in individuals and other factors associated with AD, such as physical biomarker load.


Assuntos
Doença de Alzheimer/diagnóstico , Biomarcadores/análise , Disfunção Cognitiva/diagnóstico , Aprendizagem/fisiologia , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Progressão da Doença , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Fragmentos de Peptídeos/metabolismo
10.
Eur Arch Otorhinolaryngol ; 278(3): 755-761, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32621245

RESUMO

PURPOSE: TNM8 introduced a new staging system for HPV positive oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to investigate whether the changes made in TNM8 offer the perceived benefit in prognostication when compared to TNM7 in a specific patient population in the North East of England. METHODS: A retrospective cohort comparison study of all patients with HPV positive OPSCC (n = 106) through the Newcastle Head and Neck MDT between January 2012 to December 2014. Overall survival (OS) and Disease specific survival (DSS) data at 3 years was gathered for both TNM7 and TNM8. Log rank test was used to compare survival curves. Harrell's C-index adjusted for age and smoking status was used to assess prognostic ability of the two staging methods. RESULTS: TNM8 downstages disease (TNM7 stage IV patients n = 74, TNM8 stage IV patients n = 2) but gives a more even distribution of patients across disease stages. Survival for TNM8 stage II and III is similar. In our small cohort, the log-rank test detected differences in OS between stages for both scoring methods (TNM7 p = 0.006, TNM8 p < 0.001) and similarly for DSS (TNM7 p = 0.001, TNM8 p < 0.001). Harrell's C-index was similar for both models for OS (TNM7 0.71, TNM8 0.71) and DSS (TNM7 0.74, TNM8 0.70). CONCLUSION: TNM8 downstages disease and prognosticates well for stage I disease but does not differentiate between stage II and III disease when compared to TNM7. Further adaptation is required to address this to make TNM8 a more accurate prognostic tool.


Assuntos
Alphapapillomavirus , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Inglaterra , Humanos , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/etiologia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Reino Unido/epidemiologia
12.
Br J Dermatol ; 182(2): 434-443, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31111470

RESUMO

BACKGROUND: Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which can help shape management. OBJECTIVES: To characterize the frequency of different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype and genotype-outcome associations. METHODS: We conducted a large cohort study in which we undertook MC1R genotyping from blood, and high-sensitivity genotyping of NRAS and BRAF hotspots in 156 naevus biopsies from 134 patients with CMN [male 40%; multiple CMN 76%; projected adult size (PAS) > 20 cm, 59%]. RESULTS: Mosaic NRAS mutations were detected in 68%, mutually exclusive with BRAF mutations in 7%, with double wild-type in 25%. Two separate naevi were sequenced in five of seven patients with BRAF mutations, confirming clonality. Five of seven patients with BRAF mutations had a dramatic multinodular phenotype, with characteristic histology distinct from classical proliferative nodules. NRAS mutation was the commonest in all sizes of CMN, but was particularly common in naevi with PAS > 60 cm, implying more tolerance to that mutation early in embryogenesis. Facial features were less common in double wild-type patients. Importantly, the incidence of congenital neurological disease, and apparently of melanoma, was not altered by genotype; no cases of melanoma were seen in BRAF-mutant multiple CMN, however, this genotype is rare. CONCLUSIONS: CMN of all sizes are most commonly caused by mutations in NRAS. BRAF is confirmed as a much rarer cause of multiple CMN, and appears to be commonly associated with a multinodular phenotype. Genotype in this cohort was not associated with differences in incidence of neurological disease in childhood. However, genotyping should be undertaken in suspected melanoma, for guidance of treatment. What's already known about this topic? Multiple congenital melanocytic naevi (CMN) have been shown to be caused by NRAS mosaic mutations in 70-80% of cases, by BRAF mosaicism in one case report and by inference in some previous cases. There has been debate about genotypic association with different sizes of CMN, and no data on genotype-outcome. What does this study add? NRAS mosaicism was found in 68%, BRAF in 7% and double wild-type in 25% of cases of CMN. NRAS was the commonest mutation in all sizes of CMN, but was nearly universal in projected adult size > 60 cm. BRAF is often associated with a distinct multinodular clinical/histological phenotype. Adverse outcomes did not differ between genotypes on current numbers.


Assuntos
Nevo Pigmentado , Neoplasias Cutâneas , Adulto , Estudos de Coortes , Genótipo , Humanos , Masculino , Mutação/genética , Nevo Pigmentado/genética , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética
13.
J Laryngol Otol ; 133(10): 843-855, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31506113

RESUMO

BACKGROUND: Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease. METHOD: A literature search was performed using the keywords 'nasopharyngeal neoplasm', 'cetuximab' and 'Erbitux'. RESULTS: Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting. CONCLUSION: There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.

14.
AJNR Am J Neuroradiol ; 40(3): 433-439, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819773

RESUMO

BACKGROUND AND PURPOSE: Chordoid meningiomas are uncommon WHO grade II primary intracranial neoplasms that possess unique chordoid histology and follow an aggressive clinical course. Our aim was to assess the utility of qualitative MR imaging features and quantitative apparent diffusion coefficient values as distinguishing preoperative MR imaging metrics to identify and differentiate chordoid histology from other meningioma histologic subtypes. MATERIALS AND METHODS: Twenty-one patients with meningiomas with chordoid histology, which included both chordoid meningiomas (>50% chordoid histology) and meningiomas with focal chordoid histology (<50% chordoid histology) with available preoperative MR imaging examinations, including diffusion-weighted imaging, were identified. Qualitative imaging features and quantitative ADC values were compared between meningiomas with chordoid histology and 42 nonchordoid meningiomas (29 WHO grade I, eleven WHO grade II, and 2 WHO grade III). RESULTS: The median ADC (10-3mm2/s) of meningiomas with chordoid histology was significantly higher than nonchordoid meningiomas (1.16 versus 0.92, P < .001), as was the median normalized ADC (1.60 versus 1.19, P < .001). In subgroup analysis, the median and normalized ADC values of chordoid meningiomas (n = 11) were significantly higher than those in meningiomas with focal chordoid histology (n = 10, P < .001 and P < .001, respectively) or nonchordoid meningiomas (n = 42, P < .001 and <0.001, respectively). Median and normalized ADC values were not significantly different between the meningiomas with focal chordoid histology and nonchordoid meningiomas (P = .816 and .301, respectively). Among the qualitative imaging features, only DWI signal intensity was significantly associated with meningiomas with chordoid histology diagnosis. CONCLUSIONS: ADC values are higher in chordoid compared with nonchordoid meningiomas and may be used to discriminate the degree of chordoid histology in meningiomas. While qualitative MR imaging features do not strongly discriminate chordoid from nonchordoid meningiomas, DWI may allow preoperative identification of chordoid meningiomas.


Assuntos
Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Neuroimagem/métodos , Adulto , Idoso , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
15.
JPRAS Open ; 20: 35-42, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32158870

RESUMO

INTRODUCTION: Endoscopic strip craniectomy with helmeting (ESCH) has been shown to be a safe and efficacious alternative to fronto-orbital remodeling (FOR) for selected children with craniosynostosis. In addition to clinical factors, there may be economic benefits from the use of ESCH instead of FOR. METHODS: A retrospective review of 23 patients with nonsyndromic unicoronal craniosynostosis (UCS) treated with FOR was carried out at Great Ormond Street Hospital (GOSH) for Children in London, UK. Secondary data were used for the ESCH cohort from a paper published by Jimenez and Barone (2013). Data were collected on surgical time, transfusion rates, length of hospital stay, adverse event rates, reintervention rates, and overall costs. Costs were categorized and then assigned to the appropriate data sets. RESULTS: The mean age of patients undergoing FOR (vs. ESCH) was 17.4 mo (vs. 3.1 mo) with a mean surgical time of 234 min (vs. 55 min), mean transfusion volume of 221.6 mL (vs. 80.0 mL), mean transfusion rate of 14/23 (vs. 2/115), and a total immediate overnight stay of 3.13 days (vs. 97% next-day discharge). The FOR group had a higher adverse event rate (5/23 vs. 4/115, p=<0.005) and a higher number requiring extraocular muscle surgery (4/23 vs. 7/109, p=0.16). There was a substantial difference in overall costs between the two groups. Total variance cost for the FOR group was £7436.5 vs. £4951.35, representing a cost difference of £2485.15 over the 24-month study period. CONCLUSION: ESCH, in comparison to FOR, appears as a more economical method in the management of USC patients, as well as having clinical benefits including reduced adverse event rate and improved ophthalmic outcomes.

16.
Haemophilia ; 24(5): e301-e311, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30004613

RESUMO

INTRODUCTION: Evaluating treatment success in patients with haemophilia A (HA) remains a vigorous debate, especially concerning the interpretation of results from clinical and observational research. The benefits of short-term prophylaxis are well established, but long-term outcomes, particularly related to humanistic and economic burden, are not as well understood. AIM: We conducted a systematic literature review to evaluate the association of episodic or prophylactic bleed control with long-term clinical, humanistic and economic outcomes. METHODS: Studies published in English between 1 January 2006 and 15 December 2016 were included. Participants had HA (with or without inhibitors), received prophylactic or episodic treatment and had at least 4 years of treatment or follow-up. Results were analysed qualitatively with descriptive findings. RESULTS: A total of 2091 records were screened, resulting in 19 studies from 20 publications for inclusion. Most studies included children (84%), were limited to patients with severe disease (74%) and were conducted in Europe or North America (89%). Ten studies (53%) included patients with inhibitors. Median study follow-up ranged from 5 to 19 years. Long-term bleeding and haemarthrosis outcomes were consistently better for patients receiving prophylaxis, who also required fewer hospitalizations or surgeries. Health-related quality of life, functionality and productivity were generally more favourable in patients receiving prophylaxis. Quantitative comparisons were not feasible due to the lack of consistency in endpoint collection and reporting among studies. CONCLUSION: This systematic review confirmed that the benefits of prophylactic treatment on short-term outcomes translate to broader long-term clinical, humanistic and economic benefits. Better harmonization of data collection and outcome assessments across both registries and clinical studies is needed to allow for effective comparisons across studies and across data sources.


Assuntos
Hemofilia A/tratamento farmacológico , Qualidade de Vida/psicologia , Feminino , Humanos , Masculino , Resultado do Tratamento
17.
Physiol Res ; 67(6): 935-943, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-29750887

RESUMO

The binding of high-mobility group box-1 (HMGB-1) to the membrane receptor for advanced glycation end-products (mRAGE) is a key early mediator of non-infectious inflammation and its triggers include ischaemia/hypoxia. The effects of acute hypoxia on soluble RAGE (sRAGE) are unknown. Fourteen healthy adults (50 % women; 26.6+/-3.8 years) were assessed at baseline normoxia (T0), followed by four time-points (T90, 95, 100 and 180 min) over three hours of continuous normobaric hypoxia (NH, 4,450 m equivalent) and again 60 min after return to normoxia (T240). A 5-min exercise step test was performed during NH at T90. Plasma concentrations of HMGB-1, sRAGE VCAM-1, ICAM-1, VEGF IL-8 and IL-13 were measured using venous blood. Arterial and tissue oxygen saturations were measured using pulse oximetry (SpO(2)) and near-infrared spectroscopy (StO(2)), respectively. NH led to a significant reduction in SpO(2), StO(2), sRAGE and VEGF, which was compounded by exercise, before increasing to baseline values with normoxic restoration (T240). NH-exercise led to a paired increase in HMGB-1. sRAGE inversely correlated with HMGB-1 (r=-0.32; p=0.006), heart rate (r=-0.43; p=0.004) but was not linked to SpO(2) or StO(2). In conclusion, short-term NH leads to a fall in sRAGE and VEGF concentrations with a transient rise post NH-exercise in HMGB-1.


Assuntos
Alarminas/sangue , Hipóxia/sangue , Mediadores da Inflamação/sangue , Consumo de Oxigênio/fisiologia , Adulto , Biomarcadores/sangue , Feminino , Proteína HMGB1/sangue , Humanos , Hipóxia/diagnóstico , Masculino , Estudos Prospectivos , Receptor para Produtos Finais de Glicação Avançada/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
19.
Eur J Appl Physiol ; 118(3): 647-656, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29353321

RESUMO

Criterion data for total energy expenditure (TEE) in elite rugby are lacking, which prediction equations may not reflect accurately. This study quantified TEE of 27 elite male rugby league (RL) and rugby union (RU) players (U16, U20, U24 age groups) during a 14-day in-season period using doubly labelled water (DLW). Measured TEE was also compared to estimated, using prediction equations. Resting metabolic rate (RMR) was measured using indirect calorimetry, and physical activity level (PAL) estimated (TEE:RMR). Differences in measured TEE were unclear by code and age (RL 4369 ± 979; RU 4365 ± 1122; U16, 4010 ± 744; U20, 4414 ± 688; U24, 4761 ± 1523 Kcal day- 1). Differences in PAL (overall mean 2.0 ± 0.4) were unclear. Very likely differences were observed in RMR by code (RL 2366 ± 296; RU 2123 ± 269 Kcal day- 1). Differences in relative RMR between U20 and U24 were very likely (U16, 27 ± 4; U20, 23 ± 3; U24, 26 ± 5 Kcal kg- 1 day- 1). Differences were observed between measured and estimated TEE, using Schofield, Cunningham and Harris-Benedict equations for U16 (187 ± 614, unclear; - 489 ± 564, likely and - 90 ± 579, unclear Kcal day- 1), U20 (- 449 ± 698, likely; - 785 ± 650, very likely and - 452 ± 684, likely Kcal day- 1) and U24 players (- 428 ± 1292; - 605 ± 1493 and - 461 ± 1314 Kcal day- 1, all unclear). Rugby players have high TEE, which should be acknowledged. Large inter-player variability in TEE was observed demonstrating heterogeneity within groups, thus published equations may not appropriately estimate TEE.


Assuntos
Calorimetria/métodos , Metabolismo Energético , Futebol Americano/fisiologia , Adolescente , Calorimetria/normas , Óxido de Deutério/farmacocinética , Humanos , Masculino , Isótopos de Oxigênio/farmacocinética , Adulto Jovem
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