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Five new species of the noctuid genus Leucania in Central America are described: L. mopan Adams and McCabe, sp. nov., L. merga Adams and McCabe, sp. nov., L. championi Adams and McCabe, sp. nov., L. colorada McCabe and Adams, sp. nov., L. sororia McCabe and Adams, sp. nov. The internal genitalia are key to resolving the taxonomy in this genus; in particular, the morphology of the male everted endophallus (vesica) and the female bursa copulatrix jointly resolve taxonomic confusion among cryptic species near L. albifasciata, L. oaxacana and L. humidicola. We recognize the valvular pore plate and the "poma" (bubble-like structure at base of valvae) as generic synapomorphies for Leucania. Lappets (inflatable pouches on the outer aspect of the valvae) are newly described. Descriptions and color illustrations of the imagos, male valvae, everted endophalli, and the female bursae copulatrix are provided for all newly described species and selected congeners to aid identification. Additional nomenclatorial actions are: Leucania complicata Strecker, 1898 rest. stat.; Leucania februalis Hill, 1924 syn. nov., a junior synonym of L. humidicola; Leucania elephas Troubridge 2020 syn. nov., a junior synonym of L. humidicola.
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Lepidópteros , Mariposas , Feminino , Masculino , Animais , Genitália , América Central , Distribuição AnimalRESUMO
This report presents testing of a prototype cantilevered liquid-nitrogen-cooled silicon mirror. This mirror was designed to be the first mirror for the new soft X-ray beamlines to be built as part of the Advanced Light Source Upgrade. Test activities focused on fracture, heat transfer, modal response and distortion, and indicated that the mirror functions as intended.
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PURPOSE: The recommended duration of adjuvant fluoropyrimidine and oxaliplatin chemotherapy for patients with stage III colon cancer is based on tumor classification into clinically low-risk (T1-3 N1) and high-risk (T4 or N2) groups. We determined whether Immunoscore can enhance prognostication within these risk groups. MATERIALS AND METHODS: Patients with stage III colon carcinomas (N = 600) were randomly selected from the infusional fluorouracil, leucovorin, and oxaliplatin arm of adjuvant trial NCCTG N0147 (Alliance for Clinical Trials in Oncology). Tumors were evaluated for Immunoscore that quantifies CD3+ and CD8+ T-cell densities in the tumor center and invasive margin by digital image analysis. Disease-free survival (DFS) by Immunoscore was analyzed using a multivariable Cox regression model in each risk group with adjustment for covariates including KRAS, BRAFV600E, and mismatch repair status. RESULTS: Of 559 cancers with Immunoscore data, 299 (53.5%) were classified as clinically low-risk (T1-3 N1) and 260 (46.5%) as clinically high-risk (T4 and/or N2). Among patients with low-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors had significantly worse 5-year DFS rates (77.5% v 91.8%; hazard ratio, 1.70; 95% CI, 1.03 to 2.79; P = .037). Among patients with high-risk tumors, those with Immunoscore-Low versus Immunoscore-High tumors also had significantly worse DFS (55.3% v 70.3%; hazard ratio, 1.65; 95% CI, 1.11 to 2.47; P = .013). Tumors that were low-risk/Immunoscore-Low had similar outcomes as did tumors that were high-risk/Immunoscore-High (P = .174). Prognostication was significantly improved in multivariable models where Immunoscore was added to clinical risk parameters and limited biomarkers (likelihood ratio test P = .0003). CONCLUSION: Immunoscore can refine patient prognosis beyond clinical risk group classification, suggesting its potential utility for adjuvant decision making.
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Carcinoma , Neoplasias do Colo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , PrognósticoRESUMO
The genus Athyrma Hbner, [1823] 1816 is revised, with a generic re-description and transcriptions of original descriptions (with translations) of all described species provided. Sixteen Athyrma species are recognized in this paper. Nine species are new: A. brigittae Adams McCabe sp. nov., A. tapichensis Adams McCabe, sp. nov., A. urbanae Adams McCabe, sp. nov., A. yasuni Adams McCabe, sp. nov., A. ciboney McCabe Adams, sp. nov., A. cryani McCabe Adams, sp. nov., A. itatiaia McCabe Adams, sp. nov., A. romacki McCabe Adams, sp. nov., and A. svensoni McCabe Adams, sp. nov. Taxonomic changes are as follows: Athyrma antica Schaus, 1912, syn. nov., a junior synonym of A. nodosa; A. cunesema Hampson, 1926, syn. nov., a junior synonym of A. cunesema; Athyrma cordigera Walker, 1869, comb. nov., syn. nov., a junior synonym of Celiptera levina Stoll, 1781. A lectotype is designated for A. adjutrix (Cramer, 1780). Neotypes are designated for four species: Athyrma nodosa Mschler, 1880, A. orbana Mschler, 1880, A. tuberosa (Felder and Rogenhofer, 1874), and A. ganglio Hbner, [1831] 1825. Athyrma ganglio Hbner, [1831] 1825, rest. stat. and A. dormitrix Guene in Boisduval and Guene, 1852, rest. stat. are removed from synonymy and restored as valid species. Athyrma has been associated with the Eulepidotinae however is here tentatively assigned to Erebinae: Poaphilini because of its similarity to Mimophisma Hampson, 1926. Illustrations of male and female adult habitus, ultimate instar larva, dissections of male and female external and internal genitalia are provided. Athyrma misera Butler, 1879 is removed from Athyrma and placed in Ezra gen. nov. Nymbis resecta Dognin, 1912 is removed from its current placement in Athyrma and placed in Facies gen. nov. Checklists of all three genera are provided.
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Mariposas , Animais , Feminino , Genitália , Larva , MasculinoRESUMO
Background: Adipocyte-derived adiponectin may play a role in the host inflammatory response to cancer. We examined the association of plasma adiponectin with the density of tumor-infiltrating lymphocytes (TILs) in colon cancers and with vitamin D, clinicopathological features, and patient survival. Methods: Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon cancer who received FOLFOX-based adjuvant chemotherapy (NCCTG N0147 [Alliance]). TIL densities were determined in histopathological sections. Associations with disease-free survival (DFS), time to recurrence, and overall survival were evaluated by multivariable Cox regression adjusting for potential confounders (ie, body mass index, race, TILs, and N stage). All statistical tests were 2-sided. Results: We found a statistically significant reduction in adiponectin, but not 25(OH)D, levels in tumors with high vs low TIL densities (median = 6845 vs 8984 ng/mL; P = .04). A statistically significant reduction in adiponectin was also observed in obese (body mass index >30 kg/m2) vs nonobese patients (median = 6608 vs 12 351 ng/mL; P < .001), in men vs women (median = 8185 vs 11 567 ng/mL; P < .001), in Blacks vs Whites or Asians (median = 6412 vs 8847 vs 7858 ng/mL; P < .03), and in those with fewer lymph node metastases (N1 vs N2: median = 7768 vs 9253 ng/mL; P = .01). Insufficiency of 25(OH)D (<30 ng/mL) was detected in 291 (48.5%) patients. In multivariable analyses, neither adiponectin nor 25(OH)D were associated with a statistically significant difference in DFS, overall survival , or time to recurrence in models adjusted for potential confounders. We found a statistically significant association of TILs with prognosis, yet no such interaction was observed for the association of adiponectin with TILs for DFS. Conclusions: Lower circulating adiponectin levels were associated with a statistically significant increase in TIL densities in colon cancers, indicating an enhanced antitumor immune response. In contrast to TILs, neither adiponectin nor 25(OH)D was independently prognostic.
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Adiponectina/sangue , Neoplasias do Colo/imunologia , Linfócitos do Interstício Tumoral/citologia , Vitamina D/análogos & derivados , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Índice de Massa Corporal , Quimioterapia Adjuvante , Neoplasias do Colo/sangue , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Metástase Linfática , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Compostos Organoplatínicos/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Grupos Raciais , Fatores Sexuais , Vitamina D/sangueRESUMO
Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5-40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 °C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5-8 h varying exposure times; second: varying dose rates of 0.5-8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in ≥ 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 °C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 °C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 °C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.
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Células Sanguíneas/metabolismo , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos da radiação , Laboratórios , Doses de Radiação , Exposição à Radiação , Raios X/efeitos adversos , Relação Dose-Resposta à Radiação , Humanos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia. METHODS: Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring. RESULTS: A sustained reduction in relative limb blood supply (P < 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period. CONCLUSION: These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD.
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Modelos Animais de Doenças , Membro Posterior/fisiopatologia , Isquemia/tratamento farmacológico , Quercetina/farmacologia , Animais , Apolipoproteínas E/deficiência , Isquemia/cirurgia , Masculino , Camundongos , Doença Arterial Periférica/patologia , Desempenho Físico FuncionalRESUMO
BACKGROUND: The American Joint Committee on Cancer staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer. METHODS: Patient (n = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, sex, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness, KRAS/BRAF, mismatch repair, and Immunoscore (CD3+, CD8+ T-cell densities). After determining optimal functional form (continuous or categorical) and within Cox models, backward selection was performed to analyze all variables as candidate predictors. All statistical tests were two-sided. RESULTS: Poorer DFS was found for tumors that were T4 vs T3 (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.19 to 2.60; P = .004), right- vs left-sided (HR = 1.52, 95% CI = 1.14 to 2.04; P = .005), BRAF V600E (HR = 1.74, 95% CI = 1.26 to 2.40; P < .001), mutant KRAS (HR = 1.66, 95% CI = 1.08 to 2.55; P = .02), and low vs high Immunoscore (HR = 1.69, 95% CI = 1.22 to 2.33; P = .001) (all P < .02). Increasing numbers of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both Ps< .0001). After number of +LNs, T stage, and BRAF/KRAS, Immunoscore was the most informative predictor of DFS shown multivariately. Among T1-3 N1 tumors, Immunoscore was the only variable associated with DFS that achieved statistical significance. A nomogram was generated to determine the likelihood of being recurrence-free at 3 years. CONCLUSIONS: The Immunoscore can enhance the accuracy of survival prediction among patients with stage III colon cancer.
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OBJECTIVES: United Nations member states agreed Agenda 2030 and the Sustainable Development Goals (SDGs) in 2015. Countries report their progress through Voluntary National Reviews. In this paper, we look at the extent to which the World Health Organisation (WHO) Europe SDG Roadmap (the Roadmap) on Agenda 2030 implementation is reflected in the first 20 Voluntary National Reviews (VNRs) submitted from the WHO European region. In particular, we wanted to look at how integrated the three dimensions of sustainable development were, the identification of health co-benefits and potential-added value from the health sector. STUDY DESIGN: This was a semi-quantitative analysis of 20 VNRs using an ordinal scale (no evidence, limited evidence, good evidence). Results are presented as frequency tables by criteria and by country. METHODS: We devised an assessment template consisting of 41 criteria based on the nine key areas and a selection of the proposed areas for action in the Roadmap. Each VNR was then assessed and scored against these criteria to produce country-specific and average scores for each of the nine key areas and the 25 measures we selected. RESULTS: Countries generally have good evidence on key areas such as governance, monitoring, leaving no-one behind and multipartner cooperation. They have less evidence on the key areas of health determinants, healthy settings, health literacy and investing for health. Many countries link the economic and environmental dimensions of sustainable development but not the interplay with the social (health and well-being) dimension. Some countries specifically highlighted commitments to support developing nations but few recognised the impact of domestic policies on planetary boundaries or the health of future generations. CONCLUSIONS: We found little evidence that the health sector has had a major strategic influence on actions which affect wider determinants (or health co-benefits). The WHO Europe SDG Roadmap offers a means and an opportunity for redressing this weakness, but this may require health professionals to work within their communities across all three dimensions of sustainable development.
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Nível de Saúde , Desenvolvimento Sustentável , Europa (Continente) , Humanos , Organização Mundial da SaúdeRESUMO
BACKGROUND AND OBJECTIVE: Model-based lung mechanics monitoring can provide clinically useful information for guiding mechanical ventilator treatment in intensive care. However, many methods of measuring lung mechanics are not appropriate for both fully and partially sedated patients, and are unable provide lung mechanics metrics in real-time. This study proposes a novel method of using lung mechanics identified during passive expiration to estimate inspiratory lung mechanics for spontaneously breathing patients. METHODS: Relationships between inspiratory and expiratory modeled lung mechanics were identified from clinical data from 4 fully sedated patients. The validity of these relationships were assessed using data from a further 4 spontaneously breathing patients. RESULTS: For the fully sedated patients, a linear relationship was identified between inspiratory and expiratory elastance, with slope 1.04 and intercept 1.66. The r value of this correlation was 0.94. No cohort-wide relationship was determined for airway resistance. Expiratory elastance measurements in spontaneously breathing patients were able to produce reasonable estimates of inspiratory elastance after adjusting for the identified difference between them. CONCLUSIONS: This study shows that when conventional methods fail, typically ignored expiratory data may be able to provide clinicians with the information needed about patient condition to guide MV therapy.
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Expiração , Inalação , Respiração , Resistência das Vias Respiratórias , Humanos , Modelos Biológicos , Respiração ArtificialRESUMO
OBJECTIVES: To suggest how public health systems and the health sector can utilise the United Nation (UN) sustainable development goals (SDGs) to address climate change and other threats to future health and deliver immediate public health benefits. STUDY DESIGN AND METHODS: We examined UN and World Health Organisation guidance on SDGs and other published texts on systems thinking, integration, universality and co-benefits. RESULTS AND CONCLUSIONS: The UN SDGs are a set of globally agreed objectives to end poverty, protect all that makes the planet habitable and ensure that all people enjoy peace and prosperity. The SDGs integrate the three dimensions of sustainable development (economic, environmental and social), they apply to high-income countries as well as developing countries and there are mechanisms to hold countries to account. There are three crucial issues for public health. First, a systems approach to future proof health and social justice. Second, an evidence-based approach to aid communication, framing and engagement. And, third, the importance of interventions that deliver health co-benefits (i.e. both immediate and long-term benefits to health, equity and prosperity). The SDGs present public health professionals with an important opportunity to create the right conditions for a better future through the organised efforts of society.
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Mudança Climática , Saúde Pública , Desenvolvimento Sustentável , Saúde Global , Política de Saúde , Humanos , Nações UnidasRESUMO
MOTIVATION: Non-coding rare variants (RVs) may contribute to Mendelian disorders but have been challenging to study due to small sample sizes, genetic heterogeneity and uncertainty about relevant non-coding features. Previous studies identified RVs associated with expression outliers, but varying outlier definitions were employed and no comprehensive open-source software was developed. RESULTS: We developed Outlier-RV Enrichment (ORE) to identify biologically-meaningful non-coding RVs. We implemented ORE combining whole-genome sequencing and cardiac RNAseq from congenital heart defect patients from the Pediatric Cardiac Genomics Consortium and deceased adults from Genotype-Tissue Expression. Use of rank-based outliers maximized sensitivity while a most extreme outlier approach maximized specificity. Rarer variants had stronger associations, suggesting they are under negative selective pressure and providing a basis for investigating their contribution to Mendelian disorders. AVAILABILITY AND IMPLEMENTATION: ORE, source code, and documentation are available at https://pypi.python.org/pypi/ore under the MIT license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Genômica , Software , Criança , Documentação , Humanos , Incerteza , Sequenciamento Completo do GenomaRESUMO
OBJECTIVES: Tuberculosis (TB) is a serious re-emergent public health problem in the UK. In response to rising case incidence a National TB Strain-Typing Service based on molecular strain-typing was established. This facilitates early detection and investigation of clusters, targeted public health action, and prevention of further transmission. We review the added public health value of investigating molecular TB strain-typed (ST) clusters. METHODS: A structured questionnaire for each ST cluster investigated in England between 1 January 2010 and 30 June 2013 was completed. Questions related to epidemiological links and public health action and the perceived benefits of ST cluster investigation. RESULTS: There were 278 ST cluster investigations (CIs) involving 1882 TB cases. Cluster size ranged from 2 to 92. CIs identified new epidemiological links in 36% of clusters; in 18% STs were discordant refuting transmission thought to have occurred. Additional public health action was taken following 23% of CI. CONCLUSIONS: We found positive benefits of TB molecular ST and CI, in identifying new epidemiological links between cases and taking public health action and in refuting transmission and saving resources. This needs to be translated to a decrease in transmission to provide evidence of public health value in this low prevalence high resource setting.
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Surtos de Doenças , Saúde Pública/estatística & dados numéricos , Tuberculose/epidemiologia , Análise por Conglomerados , Inglaterra/epidemiologia , Humanos , Tipagem Molecular , Mycobacterium tuberculosis/classificação , Inquéritos e Questionários , Tuberculose/prevenção & controle , Tuberculose/transmissãoRESUMO
BACKGROUND AND OBJECTIVES: Mechanical ventilation (MV) is a primary therapy for patients with acute respiratory failure. However, poorly selected ventilator settings can cause further lung damage due to heterogeneity of healthy and damaged alveoli. Varying positive-end-expiratory-pressure (PEEP) to a point of minimum elastance is a lung protective ventilator strategy. However, even low levels of PEEP can lead to ventilator induced lung injury for individuals with highly inflamed pulmonary tissue. Hence, models that could accurately predict peak inspiratory pressures after changes to PEEP could improve clinician confidence in attempting potentially beneficial treatment strategies. METHODS: This study develops and validates a physiologically relevant respiratory model that captures elastance and resistance via basis functions within a well-validated single compartment lung model. The model can be personalised using information available at a low PEEP to predict lung mechanics at a higher PEEP. Proof of concept validation is undertaken with data from four patients and eight recruitment manoeuvre arms. RESULTS: Results show low error when predicting upwards over the clinically relevant pressure range, with the model able to predict peak inspiratory pressure with less than 10% error over 90% of the range of PEEP changes up to 12 cmH2O. CONCLUSIONS: The results provide an in-silico model-based means of predicting clinically relevant responses to changes in MV therapy, which is the foundation of a first virtual patient for MV.
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Modelos Biológicos , Respiração Artificial/métodos , Mecânica Respiratória , Interface Usuário-Computador , Adulto , Idoso , Resistência das Vias Respiratórias/fisiologia , Simulação por Computador , Feminino , Humanos , Complacência Pulmonar/fisiologia , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva/efeitos adversos , Respiração com Pressão Positiva/métodos , Respiração com Pressão Positiva/estatística & dados numéricos , Respiração Artificial/efeitos adversos , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório/terapia , Mecânica Respiratória/fisiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controleRESUMO
Objectives To compare the health status concerns of patients with systemic lupus erythematosus (SLE) and of their physicians. Methods Cross-sectional questionnaire study of SLE patients and their treating physicians at a tertiary disease-specific outpatient clinic. Patients and physicians completed a questionnaire regarding their concern about specific disease manifestations and impact on quality of life. For each item, degree of concern was rated on a five-point Likert scale and summarized as median (interquartile range). Ratings between patients and physicians were compared using Mann-Whitney U tests. Results A total of 84 patients and 21 physicians participated. Patients' predominant concerns centred on function and fatigue, whereas physicians' concerns focused on SLE-related organ complications. Of the 10 highest ranked patient concerns, only two were common to the 10 highest ranked physician concerns, while physicians rated seven significantly differently; all 10 highest ranked physician concerns were rated significantly lower by patients. The three highest ranked patient concerns (fatigue, pain and feeling worn out) were routinely assessed by 47.6%, 42.9% and 9.5% of physicians, respectively. Conclusion There was significant discordance between SLE patient and physician health status concerns. Items which were ranked highly by patients were not assessed consistently by physicians, highlighting a significant gap in healthcare communication.
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Fadiga/psicologia , Nível de Saúde , Lúpus Eritematoso Sistêmico/fisiopatologia , Dor/psicologia , Medidas de Resultados Relatados pelo Paciente , Adulto , Instituições de Assistência Ambulatorial , Austrália , Estudos Transversais , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Médicos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Centros de Atenção TerciáriaRESUMO
OBJECTIVES: To establish the current use of granulocyte transfusions in haematology patients and explore interest in further research. BACKGROUND: Granulocytes may be used for the treatment of severe infection in neutropenic patients or for primary or secondary prophylaxis. Clinical utility of granulocyte transfusions is unclear, and recent studies have demonstrated equivocal outcomes. Pooled granulocytes are the main granulocyte product used in England and Wales, but there are no data on the patterns of use and little consensus on accepted indications. METHODS: A survey was distributed to UK hospitals delivering intensive chemotherapy. Clinical scenarios were posed, with further questions on clinician experience of using granulocytes, availability of the product, barriers to use and interest in further research. RESULTS: The response rate was 57%; 34·9% of all responses were from allogeneic stem cell transplant centres. Paediatric centres comprised 9·5% respondents, and 19% centres had access to apheresis granulocytes. Of respondents, 58·7% had used granulocytes in the last 3 years, 89·2% of whom used granulocytes to treat refractory infection. There was little consensus on use of granulocytes in the given clinical scenarios even when patients clearly met national guideline criteria. Paediatric centres were overall more likely to recommend granulocyte use. The most frequently identified barrier to use of granulocytes was lack of evidence of effect. Of the respondents, 75% indicated a willingness to participate in further research. CONCLUSION: There remains a lack of consistency about use of granulocytes, which is unsurprising given the lack of clinical data to support their efficacy. We did, however, demonstrate a willingness to participate in further research.
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Granulócitos , Transfusão de Leucócitos , Neutropenia/epidemiologia , Neutropenia/terapia , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , País de Gales/epidemiologiaRESUMO
OBJECTIVE: Investigating a large and ethnically diverse cohort from the Pacific region, we aimed to replicate and extend the recently reported findings that a CREBRF genetic variant is strongly associated with body mass index in Samoans. METHODS: A birth cohort of more than six thousand children was utilised. In this study, genotyping of two markers (rs12513649 and rs373863828) was undertaken in Maori, Pacific, European and Asian individuals in the cohort. RESULTS: We report that these CREBRF genetic variants are not confined to Samoans but are prevalent in all other Pacific populations sampled, including Maori. We found that the rs373863828 variant was significantly associated with growth at 4 years of age. On average, we observed allele-specific increases in weight (P=0·004, +455 g, s.e. 0.158), height (P=0·007, +0·70 cm, s.e. 0.26) and waist circumference (P=0·004, +0·70 cm, s.e. 0.24) at 4 years of age. The rs373863828 variant was not associated with birth weight (P=0·129). CONCLUSIONS: We replicated the finding that a CREBRF variant is associated with increased body mass. We then built on the original findings by demonstrating the prevalence of the rs12513649 and rs373863828 variants in multiple Pacific population groups and by demonstrating that the rs373863828 variant is associated with growth in early childhood. Pacific population groups experience a disproportionately high burden of obesity, starting in early childhood. This new knowledge offers potential for evidence-based interventions aimed at establishing healthy growth trajectories from the earliest possible age.