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BACKGROUND: Cardiovascular disease (CVD)-related mortality has declined substantially in the United Kingdom (UK) in recent decades, but the continued relevance of conventional risk factors for prediction of CVD mortality throughout the life-course is uncertain. We compared the 10-year risks and lifetime risks of CVD mortality associated with conventional risk factors recorded in middle and old age. METHODS: The Whitehall study was a prospective study of 19,019 male London civil servants (mean age 52 years) when enrolled in 1967-1970 and followed-up for 50 years for cause-specific mortality. In 1997, 7044 (83%) survivors (mean age 77 years) were re-surveyed. The 10-year and lifetime risks of CVD mortality were estimated by levels of CVD risk factors recorded in middle-age and old-age, respectively. RESULTS: By July 2020, 97% had died (22%, 51% and 80% before age 70, 80 and 90 years, respectively) and 7944 of 17,673 deaths (45%) were from CVD. The 10-year and lifetime risks of CVD death increased linearly with higher levels of CVD risk factors recorded in middle-age and in old-age. Individuals in the top versus bottom 5% of CVD risk scores in middle age had a 10.3% (95% CI:7.2-13.4) vs 0.6% (0.1-1.2) 10-year risk of CVD mortality, a 61.4% (59.4-65.3) vs 31.3% (24.1-34.5) lifetime risk of CVD mortality and a 12-year difference in life expectancy from age 50 years. The corresponding differences using a CVD risk score in old-age were 11.0% (4.4-17.5) vs 0.8% (0.0-2.2) for 10-year risk and 42.1% (28.2-50.0) vs 30.3% (6.0-38.0) for lifetime risk of CVD mortality and a 6-year difference in life expectancy from age 70 years. CONCLUSIONS: Conventional risk factors remained highly predictive of CVD mortality and life expectancy through the life-course. The findings highlight the relevance of estimation of both lifetime risks of CVD and 10-year risks of CVD for primary prevention of CVD.
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Doenças Cardiovasculares , Pessoa de Meia-Idade , Humanos , Masculino , Idoso , Criança , Londres/epidemiologia , Estudos Prospectivos , Seguimentos , Fatores de Risco , Doenças Cardiovasculares/prevenção & controleRESUMO
Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.
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The ß-adrenergic agonists salbutamol and ephedrine have proven to be effective as therapies for human disorders of the neuromuscular junction, in particular many subsets of congenital myasthenic syndromes. However, the mechanisms underlying this clinical benefit are unknown and improved understanding of the effect of adrenergic signalling on the neuromuscular junction is essential to facilitate the development of more targeted therapies. Here, we investigated the effect of salbutamol treatment on the neuromuscular junction in the ColQ deficient mouse, a model of end-plate acetylcholinesterase deficiency. ColQ-/- mice received 7 weeks of daily salbutamol injection, and the effect on muscle strength and neuromuscular junction morphology was analysed. We show that salbutamol leads to a gradual improvement in muscle strength in ColQ-/- mice. In addition, the neuromuscular junctions of salbutamol treated mice showed significant improvements in several postsynaptic morphological defects, including increased synaptic area, acetylcholine receptor area and density, and extent of postjunctional folds. These changes occurred without alterations in skeletal muscle fibre size or type. These findings suggest that ß-adrenergic agonists lead to functional benefit in the ColQ-/- mouse and to long-term structural changes at the neuromuscular junction. These effects are primarily at the postsynaptic membrane and may lead to enhanced neuromuscular transmission.
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Acetilcolinesterase/genética , Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Colágeno/genética , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Síndromes Miastênicas Congênitas/genética , Junção Neuromuscular/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Agrina/metabolismo , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Distroglicanas/metabolismo , Camundongos , Camundongos Knockout , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/ultraestrutura , Proteínas Musculares/metabolismo , Debilidade Muscular/terapia , Síndromes Miastênicas Congênitas/tratamento farmacológico , Junção Neuromuscular/diagnóstico por imagem , Junção Neuromuscular/metabolismo , Receptores Colinérgicos , Transdução de Sinais , Transmissão Sináptica/fisiologiaRESUMO
BACKGROUND: Recommendations for screening patients with lower-extremity arterial disease (LEAD) to detect asymptomatic carotid stenosis (ACS) are conflicting. Prediction models might identify patients at high risk of ACS, possibly allowing targeted screening to improve preventive therapy and compliance. METHODS: A systematic search for prediction models for at least 50 per cent ACS in patients with LEAD was conducted. A prediction model in screened patients from the USA with an ankle : brachial pressure index of 0.9 or less was subsequently developed, and assessed for discrimination and calibration. External validation was performed in two independent cohorts, from the UK and the Netherlands. RESULTS: After screening 4907 studies, no previously published prediction models were found. For development of a new model, data for 112 117 patients were used, of whom 6354 (5.7 per cent) had at least 50 per cent ACS and 2801 (2.5 per cent) had at least 70 per cent ACS. Age, sex, smoking status, history of hypercholesterolaemia, stroke/transient ischaemic attack, coronary heart disease and measured systolic BP were predictors of ACS. The model discrimination had an area under the receiver operating characteristic (AUROC) curve of 0.71 (95 per cent c.i. 0.71 to 0.72) for at least 50 per cent ACS and 0.73 (0.72 to 0.73) for at least 70 per cent ACS. Screening the 20 per cent of patients at greatest risk detected 12.4 per cent with at least 50 per cent ACS (number needed to screen (NNS) 8] and 5.8 per cent with at least 70 per cent ACS (NNS 17). This yielded 44.2 and 46.9 per cent of patients with at least 50 and 70 per cent ACS respectively. External validation showed reliable discrimination and adequate calibration. CONCLUSION: The present risk score can predict significant ACS in patients with LEAD. This approach may inform targeted screening of high-risk individuals to enhance the detection of ACS.
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Doenças Assintomáticas , Estenose das Carótidas/diagnóstico , Isquemia Crônica Crítica de Membro/diagnóstico , Extremidade Inferior/irrigação sanguínea , Programas de Rastreamento/métodos , Estenose das Carótidas/complicações , Isquemia Crônica Crítica de Membro/complicações , Humanos , Cooperação do Paciente , Fatores de RiscoRESUMO
Cardiac surgical patients with anaemia experience increased morbidity and mortality. Iron deficiency is the most common cause of pre-operative anaemia in this group. We designed and implemented the Cardiff Pathway, a pre-assessment and treatment pathway to identify cardiac surgical patients with anaemia and iron deficiency. Patients identified with anaemia and/or iron deficiency (Hb < 130 g.l-1 and ferritin < 100 µg.l-1 ) were offered intravenous iron infusion 20 mg.kg-1 pre-operatively. Treatment success was defined as Hb ≥ 130g.l-1 on the day of surgery. We analysed data from 447 patients: 300 (67%) were not anaemic; 75 (17%) were anaemic and treated with intravenous iron; and 72 (16%) were anaemic and not treated. Haemoglobin concentration increased in successfully treated anaemic patients by a mean (95%CI) of 17 (13-21) g.l-1 and they received a median (IQR [range]) of 0 (0-2 [0-15]) units of blood peri-operatively. Transfusion was avoided in 54% of the successfully treated anaemic patients, which was significantly more than the unsuccessfully treated anaemic (22%, p = 0.005) and untreated anaemic (28%, p = 0.018) patients and similar to non-anaemic patients who received a median (IQR [range] of 0 (0-1 [0-16])) units of blood and, 63% avoided transfusion). Mean (95%CI) Hb fell between pre-assessment and surgery in the untreated anaemic (-2 (0 to -4) g.l-1 ) and non-anaemic groups (-2 (-1 to -3) g.l-1 ). Twenty-one (7%) of the non-anaemic group became newly anaemic waiting for surgery. The Cardiff Pathway reliably identified patients with anaemia and iron deficiency. Anaemic patients who had their Hb restored to normal after treatment required less blood peri-operatively and over half of them required no transfusion at all.
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Anemia/patologia , Ferro/administração & dosagem , Administração Intravenosa , Idoso , Anemia/mortalidade , Anemia/cirurgia , Procedimentos Cirúrgicos Eletivos , Transfusão de Eritrócitos , Feminino , Hemoglobinas/análise , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Resultado do TratamentoRESUMO
Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway which yields precursors required for protein and lipid glycosylation. Mutations in GFPT1 and other genes downstream of this pathway cause congenital myasthenic syndrome (CMS) characterized by fatigable muscle weakness owing to impaired neurotransmission. The precise pathomechanisms at the neuromuscular junction (NMJ) owing to a deficiency in GFPT1 is yet to be discovered. One of the challenges we face is the viability of Gfpt1-/- knockout mice. In this study, we use Cre/LoxP technology to generate a muscle-specific GFPT1 knockout mouse model, Gfpt1tm1d/tm1d, characteristic of the human CMS phenotype. Our data suggest a critical role for muscle derived GFPT1 in the development of the NMJ, neurotransmission, skeletal muscle integrity and highlight that a deficiency in skeletal muscle alone is sufficient to cause morphological postsynaptic NMJ changes that are accompanied by presynaptic alterations despite the conservation of neuronal GFPT1 expression. In addition to the conventional morphological NMJ changes and fatigable muscle weakness, Gfpt1tm1d/tm1d mice display a progressive myopathic phenotype with the presence of tubular aggregates in muscle, characteristic of the GFPT1-CMS phenotype. We further identify an upregulation of skeletal muscle proteins glypican-1, farnesyltransferase/geranylgeranyltransferase type-1 subunit α and muscle-specific kinase, which are known to be involved in the differentiation and maintenance of the NMJ. The Gfpt1tm1d/tm1d model allows for further investigation of pathophysiological consequences on genes and pathways downstream of GFPT1 likely to involve misglycosylation or hypoglycosylation of NMJs and muscle targets.
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Debilidade Muscular/genética , Doenças Musculares/genética , Síndromes Miastênicas Congênitas/genética , Transferases de Grupos Nitrogenados/genética , Animais , Modelos Animais de Doenças , Expressão Gênica/genética , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante) , Glicosilação , Humanos , Camundongos , Camundongos Knockout , Debilidade Muscular/fisiopatologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Mutação , Síndromes Miastênicas Congênitas/fisiopatologia , Junção Neuromuscular/genética , Junção Neuromuscular/fisiopatologia , Transmissão Sináptica/genéticaRESUMO
This prospective study of Chinese adults demonstrated an inverse J-shaped association of number of children with risk of hip fracture in both men and postmenopausal women aged 50 years or older. Women with 2 or 3 children and men with 4 children had the lowest risk of hip fracture. INTRODUCTION: Women have higher absolute risks of fracture than men, which is believed to reflect differences in oestrogen exposure. The aim of this study was to compare the associations of number of children with risk of hip fracture between men and women aged over 50 years. METHODS: The China Kadoorie Biobank (CKB) recruited 133,399 women and 110,296 men, aged 50 years or older between 2004 and 2008. During 10-year follow-up, 2068 participants (1394 women and 674 men) suffered a hip fracture. Cox regression analysis was used to estimate sex-specific adjusted hazard ratios (HRs) and 95% CI for incident hip fracture. RESULTS: Over 98% of both subsets of men and women aged 50 or older reported having children. Women who had 2 or 3 children had the lowest risks of hip fracture compared with other groups. Compared with nulliparous women, the adjusted HR for hip fracture were 0.89 (95% CI; 0.72, 1.10) for 1 child, 0.79 (0.70, 0.90) for 2 children, 0.79 (0.72, 0.87) for 3 children, 0.81 (0.72, 0.91) for 4 children, and 0.95 (0.83, 1.10) for those with 5 or more children. The associations of number of children with hip fracture were broadly consistent in men of a similar age. CONCLUSIONS: The concordant effects of the number of children with risk of hip fracture between men and women suggest that the lower risks in multiparous women are not due to differences in oestrogen exposure or other biological effects, but may reflect residual confounding by socioeconomic or lifestyle factors.
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Fraturas do Quadril , Adulto , Idoso , Criança , China/epidemiologia , Feminino , Seguimentos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
The original version of this article, published on 25 November 2019, unfortunately contained a mistake.
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In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.
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The propagation of fast electron currents in near solid-density media was investigated via proton probing. Fast currents were generated inside dielectric foams via irradiation with a short (â¼0.6 ps) laser pulse focused at relativistic intensities (Iλ^{2}â¼4×10^{19} W cm^{-2} µm^{2}). Proton probing provided a spatially and temporally resolved characterization of the evolution of the electromagnetic fields and of the associated net currents directly inside the target. The progressive growth of beam filamentation was temporally resolved and information on the divergence of the fast electron beam was obtained. Hybrid simulations of electron propagation in dense media indicate that resistive effects provide a major contribution to field generation and explain well the topology, magnitude, and temporal growth of the fields observed in the experiment. Estimations of the growth rates for different types of instabilities pinpoints the resistive instability as the most likely dominant mechanism of beam filamentation.
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Anthropogenic environmental change is driving the rapid loss of biodiversity. Large declines in the abundance of historically common species are now emerging as a major concern. Identifying declining populations through long-term biodiversity monitoring is vital for implementing timely conservation measures. It is, therefore, critical to evaluate the likelihood that persistent long-term population trends of a given size could be detected using existing monitoring data and methods. Here, we test the power to detect declines in Australia's common landbirds using long-term citizen science monitoring. We use spatially explicit simulations of occupancy dynamics and virtual sampling, designed to mimic bird monitoring in better-sampled regions of Australia, to assess likely power in these data to detect trends relevant for conservation. We predict the statistical power for 326 common species that meet minimum requirements for monitoring data across 10 regions of Australia, estimating the number of species for which we would have a high (≥80%) chance of detecting declines of different sizes. The power to detect declines of ≥30% per decade was predicted to be high for at least one-third of the common species in 7 of 10 regions, with a total of 103 (32% of 326) unique species sufficiently monitored in at least one region. These species spanned 12 taxonomic orders, four orders of magnitude in body mass, and a broad diversity of dietary guilds, suggesting the current species pool will likely serve as robust indicators for a broad range of environmental states and pressures. Power was strongly affected by species' detectability, and power to detect even large declines was negligible when species are detected on ≤50% of visits to an occupied site. Predicted power for many species fell just short of the 80% threshold in one or more regions, which suggests an increase in effort targeting these species could greatly enhance the species and regional representation of these data. Against the backdrop of unprecedented biodiversity losses, this study shows how critical evaluation of existing monitoring schemes is valuable both for assessing the contribution of citizen science schemes to biodiversity monitoring and for designing strategic monitoring to significantly improve the knowledge these schemes provide.
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Biodiversidade , Aves , Animais , Austrália , Conservação dos Recursos Naturais , Coleta de Dados , Dinâmica PopulacionalRESUMO
Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.
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Anestesia/métodos , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Penicilinas/efeitos adversos , HumanosRESUMO
BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.
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Hipersensibilidade Imediata/diagnóstico , Complicações Intraoperatórias/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Consenso , HumanosRESUMO
OBJECTIVES: We provide descriptions and functional interpretations of 11 >2.0 Ma hominin vertebral and upper limb fossils from Sterkfontein. MATERIALS AND METHODS: We employed taphonomic methods to describe postmortem damage observed on the fossils. We used osteometric tools and measurements to generate quantitative descriptions, which were added to qualitative descriptions of the fossils. These observations were then interpreted using published data on the same skeletal elements from extant and extinct hominoid taxa. RESULTS: Six of the fossils carry carnivore tooth marks. Two vertebrae show morphologies that are consistent with fully developed lordosis of the lumbar spine, but which are not completely consistent with bipedal loading of the same intensity and/or frequency as reflected in the lumbars of modern humans. A clavicle shows a combination of humanlike and apelike features, the latter of which would have endowed its hominin with good climbing abilities. When combined, analyses of fragmentary radius and ulna fossils yield more ambiguous results. DISCUSSION: The new fossil collection presents a mix of bipedal and climbing features. It is unclear whether this mix indicates that all Sterkfontein hominins of >2.0 Ma were terrestrial bipeds who retained adaptations for climbing or whether the collection samples two differently adapted, coeval hominins, Australopithecus africanus and Australopithecus prometheus, both of which are represented at Sterkfontein by skull remains. Regardless, the significant frequency of tooth-marked fossils in the sample might indicate that predation was a selection pressure that maintained climbing adaptations in at least some Sterkfontein hominins of this period.
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Ossos do Braço/anatomia & histologia , Hominidae/anatomia & histologia , Hominidae/fisiologia , Coluna Vertebral/anatomia & histologia , Animais , Antropologia Física , Cavernas , Feminino , Fósseis , Locomoção , Masculino , África do SulRESUMO
A dual ion species plasma expansion scheme from a novel target structure is introduced, in which a nanometer-thick layer of pure deuterium exists as a buffer species at the target-vacuum interface of a hydrogen plasma. Modeling shows that by controlling the deuterium layer thickness, a composite H^{+}/D^{+} ion beam can be produced by target normal sheath acceleration (TNSA), with an adjustable ratio of ion densities, as high energy proton acceleration is suppressed by the acceleration of a spectrally peaked deuteron beam. Particle in cell modeling shows that a (4.3±0.7) MeV per nucleon deuteron beam is accelerated, in a directional cone of half angle 9°. Experimentally, this was investigated using state of the art cryogenic targetry and a spectrally peaked deuteron beam of (3.4±0.7) MeV per nucleon was measured in a cone of half angle 7°-9°, while maintaining a significant TNSA proton component.
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Intra-operative acute hypersensitivity reactions require a decision to be made regarding whether to proceed with or abandon the planned surgical procedure once the patient has stabilised. Using retrospective case controls, we examined all cases (223) of proven acute hypersensitivity reactions from 2005 to 2014 in Western Australia, in which the syndrome was recognised by the treating clinician before or during surgery, to determine whether recovery outcomes were adversely affected by proceeding with the planned procedure. Surgery proceeded in 104 patients (47%) and was abandoned in 119 (53%). The severity of acute hypersensitivity reactions was Société Française d'Anesthésie et de Réanimation grade 1 or 2 in 56 patients (25%), grade 3 in 128 (56%) and grade 4 in 39 (17%). Abandoning surgery was more common in patients with increasing severity of hypersensitivity. The rate of major hypersensitivity-related complications for all patients was zero for grade 1 and 2 reactions, 4.7% for grade 3 and 12.8% for grade 4. There were no deaths. Patients in whom surgery was completed were not observed to have a higher frequency of major hypersensitivity-related complications when compared with cases of similar severity in whom surgery was abandoned. For patients admitted to the intensive care unit, proceeding with surgery was not associated with an increased duration of mechanical ventilation of the lungs. Our results suggest that, once initial resuscitation has been achieved and if resuscitative efforts can be re-instituted if required, continuing with planned surgery in grade 1, 2 and 3 immediate hypersensitivity was not associated with poorer outcomes. After grade 3 reactions, there was a significant incidence of complications attributable to acute hypersensitivity regardless of whether surgery proceeded or was abandoned. Surgery was frequently abandoned in grade 4 immediate hypersensitivity and was associated with a high rate of complications.
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Anafilaxia/complicações , Hipersensibilidade a Drogas/complicações , Complicações Intraoperatórias/induzido quimicamente , Ressuscitação , Procedimentos Cirúrgicos Operatórios , Doença Aguda , Idoso , Anafilaxia/terapia , Estudos de Casos e Controles , Hipersensibilidade a Drogas/terapia , Feminino , Humanos , Complicações Intraoperatórias/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Austrália OcidentalRESUMO
BACKGROUND: Use of liquid biopsy for minimal invasive follow-up diagnostics of non-small-cell lung carcinomas (NSCLCs). OBJECTIVES: Systematic search for new putative blood-based hypermethylation biomarkers to discriminate NSCLC patients from patients without a malign disease. METHODS: Quantitative analysis of gene promoter DNA methylation of potential biomarkers from cfDNA (plasma) with pyrosequencing. RESULTS: cfDNA hypermethylation in plasma confirmed significant higher methylation frequencies of the candidate gene CFTR of the NSCLC patients compared to the combined control groups and to NSCLC patients after curative therapy of primary NSCLC (post-NSCLC). ROC-analysis of the best discriminatory CpGs of the CFTR promotor (CpG1-2-4) revealed a sensitivity of 52% in NSCLC patients and a specificity of 90% in the post-NSCLC group (AUC: 0.69; pâ¯< 0.05). CONCLUSIONS: Promotor hypermethylation of the potential biomarker CFTR shows a discriminatory potential for differentiation of NSCLC patients to patients without a malign disease and should further be investigated.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metilação de DNA , Humanos , Biópsia Líquida , Regiões Promotoras GenéticasRESUMO
This trial compared the effects of daily treatment with vitamin D or placebo for 1 year on blood tests of vitamin D status. The results demonstrated that daily 4000 IU vitamin D3 is required to achieve blood levels associated with lowest disease risks, and this dose should be tested in future trials for fracture prevention. INTRODUCTION: The aim of this trial was to assess the effects of daily supplementation with vitamin D3 4000 IU (100 µg), 2000 IU (50 µg) or placebo for 1 year on biochemical markers of vitamin D status in preparation for a large trial for prevention of fractures and other outcomes. METHODS: This is a randomized placebo-controlled trial in 305 community-dwelling people aged 65 years or older in Oxfordshire, UK. Outcomes included biochemical markers of vitamin D status (plasma 25-hydroxy-vitamin D [25[OH]D], parathyroid hormone [PTH], calcium and alkaline phosphatase), cardiovascular risk factors and tests of physical function. RESULTS: Mean (SD) plasma 25(OH)D levels were 50 (18) nmol/L at baseline and increased to 137 (39), 102 (25) and 53 (16) nmol/L after 12 months in those allocated 4000 IU, 2000 IU or placebo, respectively (with 88%, 70% and 1% of these groups achieving the pre-specified level of >90 nmol/L). Neither dose of vitamin D3 was associated with significant deviation outside the normal range of PTH or albumin-corrected calcium. The additional effect on 25(OH)D levels of 4000 versus 2000 IU was similar in all subgroups except for body mass index, for which the further increase was smaller in overweight and obese participants compared with normal-weight participants. Supplementation with vitamin D had no significant effects on cardiovascular risk factors or on measures of physical function. CONCLUSIONS: After accounting for average 70% compliance in long-term trials, doses of 4000 IU vitamin D3 daily may be required to achieve plasma 25(OH)D levels associated with lowest disease risk in observational studies.
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Conservadores da Densidade Óssea/administração & dosagem , Colecalciferol/administração & dosagem , Fraturas por Osteoporose/prevenção & controle , Idoso , Fosfatase Alcalina/sangue , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Cálcio/sangue , Doenças Cardiovasculares/prevenção & controle , Colecalciferol/efeitos adversos , Colecalciferol/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Fraturas por Osteoporose/sangue , Hormônio Paratireóideo/sangue , Aptidão Física , Atenção Primária à Saúde/métodos , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
BACKGROUND: Worldwide 350 million people suffer from major depression, with the majority of cases occurring in low- and middle-income countries. We examined the patterns, correlates and care-seeking behaviour of adults suffering from major depressive episode (MDE) in China. METHOD: A nationwide study recruited 512 891 adults aged 30-79 years from 10 provinces across China during 2004-2008. The 12-month prevalence of MDE was assessed by the Modified Composite International Diagnostic Interview-short form. Logistic regression yielded adjusted odds ratios (ORs) of MDE associated with socio-economic, lifestyle and health-related factors and major stressful life events. RESULTS: Overall, 0.7% of participants had MDE and a further 2.4% had major depressive symptoms. Stressful life events were strongly associated with MDE [adjusted OR 14.7, 95% confidence interval (CI) 13.7-15.7], with a dose-response relationship with the number of such events experienced. Family conflict had the highest OR for MDE (18.9, 95% CI 16.8-21.2) among the 10 stressful life events. The risk of MDE was also positively associated with rural residency (OR 1.5, 95% CI 1.4-1.7), low income (OR 2.3, 95% CI 2.1-2.4), living alone (OR 2.6, 95% CI 2.3-3.0), smoking (OR 1.4, 95% CI 1.3-1.6) and certain other mental disorders (e.g. anxiety, phobia). Similar, albeit weaker, associations were observed with depressive symptoms. Among those with MDE, about 15% sought medical help or took psychiatric medication, 15% reported having suicidal ideation and 6% reported attempting suicide. CONCLUSIONS: Among Chinese adults, the patterns and correlates of MDE were generally consistent with those observed in the West. The low rates of seeking professional help and treatment highlight the great gap in mental health services in China.
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Transtorno Depressivo Maior/epidemiologia , Conflito Familiar , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fatores Socioeconômicos , Estresse Psicológico/epidemiologia , Adulto , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Emergency cricothyrotomy is a common feature in all difficult airway algorithms. It is the final step following a 'can't intubate, can't oxygenate' scenario. It is rarely performed and has a significant failure rate. There is variation in the reported size of the cricothyroid membrane, especially across population groups. Procedural failure may result from attempting to pass a device with too large an external diameter through the cricothyroid membrane. We aimed to determine the maximum height of the cricothyroid membrane in a UK trauma population. Electronic callipers were used to measure the maximum height of the cricothyroid membrane on 482 reformatted trauma computed tomography scans, 377 (78.2%) of which were in male patients. The mean (SD) height of the cricothyroid membrane, as independently measured by two radiologists, was 7.89 (2.21) mm and 7.88 (2.22) mm in male patients, and 6.00 (1.76) mm and 5.92 (1.71) mm in female patients. The presence of concurrent tracheal intubation or cervical spine immobilisation was found not to have a significant effect on cricothyroid membrane height. The cricothyroid membrane height in the study population was much smaller than that previously reported. Practitioners encountering patients who may require an emergency surgical airway should be aware of these data. Rescue airway equipment with variety of external diameters should be immediately available.