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1.
Osteoporos Int ; 35(5): 903-909, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38448782

RESUMO

Patients who sustain a contralateral hip fracture experience significantly inferior outcomes; however, the incidence and predictors of contralateral hip fracture remain poorly understood. In the present study, 2.5% of patients sustained a contralateral hip fracture within 12 months, and socioeconomic deprivation was associated with reduced risk of contralateral hip fracture. INTRODUCTION: Hip fractures are associated with high morbidity and mortality, and patients that sustain a subsequent contralateral fracture experience inferior outcomes. The risk of contralateral fracture is highest within the first year; however, the incidence and associated factors remain poorly understood. The aims were to investigate (i) the incidence of a subsequent contralateral hip fracture within the first year, (ii) identify factors associated with an increased risk of contralateral fracture and (iii) compare early mortality risk after index versus contralateral hip fracture. METHODS: This study included all patients aged over 50 years admitted to NHS hospitals in Scotland between 1st March 2020 and 31st December 2020 (n = 5566) as routine activity of the Scottish Hip Fracture Audit (SHFA). Multivariate logistic regression was used to examine factors associated with 30-day mortality, and cox regression was used to identify factors associated with a contralateral fracture. RESULTS: During the study period 2.5% (138/5566) of patients sustained a contralateral hip fracture within 12 months of the index hip fracture. Socioeconomic deprivation was inversely associated with increased risk of contralateral fracture (odds ratio 2.64, p < 0.001), whilst advancing age (p = 0.427) and sex (p = 0.265) were not. After adjusting for significant cofounders, there was no significant difference in 30-day mortality following contralateral fracture compared to index fracture (OR 1.22, p = 0.433). CONCLUSION: One in 40 (2.5%) hip fracture patients sustained a contralateral fracture within 12 months of their index fracture, and deprivation was associated with a reduced risk of contralateral fracture. No difference in 30-day mortality was found.


Assuntos
Fraturas do Quadril , Humanos , Pessoa de Meia-Idade , Incidência , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Hospitalização , Escócia , Hospitais , Fatores de Risco , Estudos Retrospectivos
2.
Osteoporos Int ; 35(2): 353-363, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37897507

RESUMO

This nationwide study used data-linked records to assess the effect of COVID-19 vaccination among hip fracture patients. Vaccination was associated with a lower risk of contracting COVID-19 and, among COVID-positive patients, it reduced the mortality risk to that of COVID-negative patients. This provides essential data for future communicable disease outbreaks. PURPOSE: COVID-19 confers a three-fold increased mortality risk among hip fracture patients. The aims were to investigate whether vaccination was associated with: i) lower mortality risk, and ii) lower likelihood of contracting COVID-19 within 30 days of fracture. METHODS: This nationwide cohort study included all patients aged > 50 years that sustained a hip fracture in Scotland between 01/03/20-31/12/21. Data from the Scottish Hip Fracture Audit were collected and included: demographics, injury and management variables, discharge destination, and 30-day mortality status. These variables were linked to government-managed population level records of COVID-19 vaccination and laboratory testing. RESULTS: There were 13,345 patients with a median age of 82.0 years (IQR 74.0-88.0), and 9329/13345 (69.9%) were female. Of 3022/13345 (22.6%) patients diagnosed with COVID-19, 606/13345 (4.5%) were COVID-positive within 30 days of fracture. Multivariable logistic regression demonstrated that vaccinated patients were less likely to be COVID-positive (odds ratio (OR) 0.41, 95% confidence interval (CI) 0.34-0.48, p < 0.001) than unvaccinated patients. 30-day mortality rate was higher for COVID-positive than COVID-negative patients (15.8% vs 7.9%, p < 0.001). Controlling for confounders (age, sex, comorbidity, deprivation, pre-fracture residence), unvaccinated patients with COVID-19 had a greater mortality risk than COVID-negative patients (OR 2.77, CI 2.12-3.62, p < 0.001), but vaccinated COVID19-positive patients were not at increased risk of death (OR 0.93, CI 0.53-1.60, p = 0.783). CONCLUSION: Vaccination was associated with lower COVID-19 infection risk. Vaccinated COVID-positive patients had a similar mortality risk to COVID-negative patients, suggesting a reduced severity of infection. This study demonstrates the efficacy of vaccination in this vulnerable patient group, and presents data that will be valid in the management of future outbreaks.


Assuntos
COVID-19 , Fraturas do Quadril , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos de Coortes , Vacinas contra COVID-19 , Vacinação , Estudos Retrospectivos
3.
J Acoust Soc Am ; 155(3): 2199-2208, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38517262

RESUMO

The sound transmission loss (STL) of wall partitions, especially in the coincidence region, is investigated. A Mindlin plate with periodically attached masses in a periodic "supercell" pattern is analyzed theoretically and experimentally for sound attenuation. Modeling the masses as points, analytical expressions for predicting the dispersion relation and frequency bandgaps of the plate are developed. The results show that varying the distances between the masses or the masses themselves can lead to the emergence of additional lower-frequency bandgaps and slightly decrease the bandwidth of the primary complete bandgap. Additionally, a triangular periodic pattern of point masses can provide a larger complete bandgap than the conventional rectangular pattern. The results are validated by numerical analyses using the wave and finite element method. Experimental testing is conducted on large-scale plates (2.4 m × 1 m) with periodically attached masses under diffuse field conditions, demonstrating the benefits of utilizing multiple scattering to increase the STL in the coincidence region of the bare plate. The proposed approach is seen to significantly increase the STL of wall partitions in the coincidence region and provides insights into the fundamental principles of sound and vibration attenuation in complex structures based on multiple scattering.

4.
Surgeon ; 21(4): 217-224, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35624020

RESUMO

AIM: The aims were to assess the utility of: 1) virtual reality-mediated simulation, and 2) a multi-modality 'Bootcamp' in the delivery of total knee arthroplasty (TKA) teaching to orthopaedic surgical trainees. BACKGROUND: Surgical training opportunities are diminished as a result of the COVID-19 pandemic which may result in delays to training completion and gaps in the permanent workforce. Modern and technology-enhanced learning methods have been identified as having the potential to support high-quality and sustainable education. METHODS: This mixed-methods study assessed the educational benefit of two activities designed to teach TKA to junior (ST1-3) orthopaedic trainees. A multi-modality training Bootcamp was delivered that included: virtual reality (VR) and saw-bone simulation; tutorials, and case-based symposia. The VR component was delivered to different participants (surgical trainees, scrub nurses, and consultants) on a further two separate occasions. Qualitative and quantitative data were collected pertaining to utility and performance. RESULTS: Trainees reported that the Bootcamp improved comprehension of arthroplasty principles including component alignment, knee balancing, and intraoperative strategies. Case-based discussions helped develop diagnostic and decision-making skills. The VR activity improved understanding of the surgical process map, increased ability to anticipate steps, and consider the procedure strategically. All staff groups found the VR activity beneficial and would recommend it as a useful addition to a surgical department. CONCLUSION: VR-mediated simulation could augment the education of surgical trainees and scrub team staff by improving comprehension of the surgical process map. Integrated multi-modality 'Bootcamp-style' training activities constructed around trainees' needs may provide a sustainable solution to bridge the experience gap related to reduced exposure to elective orthopaedic practice.


Assuntos
COVID-19 , Ortopedia , Treinamento por Simulação , Cirurgiões , Realidade Virtual , Humanos , Ortopedia/educação , Pandemias , COVID-19/epidemiologia , Tecnologia , Competência Clínica , Treinamento por Simulação/métodos
5.
Surgeon ; 21(5): e263-e270, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36914519

RESUMO

BACKGROUND: Access to surgical training is challenging for undergraduate and early postgraduate trainees due to a greater focus on developing generic knowledge and skills, and a drive to recruit greater numbers into internal medicine and primary care. COVID-19 accelerated the declining access to surgical training environments. Our aims were to: 1) establish the feasibility of an online, specialty-specific, case-based surgical training series, and 2) evaluate its suitability for meeting the needs of trainees. METHODS: A nationwide audience of undergraduate and early postgraduate trainees were invited to a series of bespoke online case-based educational meetings in Trauma & Orthopaedics (T&O) over a six month period. The six sessions, which simulated real-world clinical meetings, were constructed by Consultant sub-specialists and involved the presentation of cases by registrars, followed by structured discussion of basic principles, radiological interpretation, and management strategies. Mixed qualitative and quantitative analyses were conducted. RESULTS: There were 131 participants (59.5% male), consisting mostly of doctors in training (58%) and medical students (37.4%). The mean quality rating was 9.0/10 (SD 1.06), further supported by qualitative analysis. 98% enjoyed the sessions, 97% reported improved knowledge of T&O, and 94% reported a direct benefit to clinical practice. There was a significant improvement in knowledge of T&O conditions, management plans, and radiological interpretation (p = <0.05). CONCLUSION: Structured virtual meetings, underpinned by bespoke clinical cases, may widen access to T&O training, increase flexibility and robustness of learning opportunities, and mitigate the effects of reduced exposure on preparation for surgical careers and recruitment.


Assuntos
COVID-19 , Educação a Distância , Ortopedia , Humanos , Masculino , Feminino , COVID-19/epidemiologia , Aprendizagem , Currículo , Competência Clínica
6.
Surgeon ; 20(6): e429-e446, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35430111

RESUMO

AIMS: This international study aimed to assess: 1) the prevalence of preoperative and postoperative COVID-19 among patients with hip fracture, 2) the effect on 30-day mortality, and 3) clinical factors associated with the infection and with mortality in COVID-19-positive patients. METHODS: A multicentre collaboration among 112 centres in 14 countries collected data on all patients presenting with a hip fracture between 1st March-31st May 2020. Demographics, residence, place of injury, presentation blood tests, Nottingham Hip Fracture Score, time to surgery, management, ASA grade, length of stay, COVID-19 and 30-day mortality status were recorded. RESULTS: A total of 7090 patients were included, with a mean age of 82.2 (range 50-104) years and 4959 (69.9%) being female. Of 651 (9.2%) patients diagnosed with COVID-19, 225 (34.6%) were positive at presentation and 426 (65.4%) were positive postoperatively. Positive COVID-19 status was independently associated with male sex (odds ratio (OR) 1.38, p = 0.001), residential care (OR 2.15, p < 0.001), inpatient fall (OR 2.23, p = 0.003), cancer (OR 0.63, p = 0.009), ASA grades 4 (OR 1.59, p = 0.008) or 5 (OR 8.28, p < 0.001), and longer admission (OR 1.06 for each increasing day, p < 0.001). Patients with COVID-19 at any time had a significantly lower chance of 30-day survival versus those without COVID-19 (72.7% versus 92.6%, p < 0.001). COVID-19 was independently associated with an increased 30-day mortality risk (hazard ratio (HR) 2.83, p < 0.001). Increasing age (HR 1.03, p = 0.028), male sex (HR 2.35, p < 0.001), renal disease (HR 1.53, p = 0.017), and pulmonary disease (HR 1.45, p = 0.039) were independently associated with a higher 30-day mortality risk in patients with COVID-19 when adjusting for confounders. CONCLUSION: The prevalence of COVID-19 in hip fracture patients during the first wave of the pandemic was 9%, and was independently associated with a three-fold increased 30-day mortality risk. Among COVID-19-positive patients, those who were older, male, with renal or pulmonary disease had a significantly higher 30-day mortality risk.


Assuntos
COVID-19 , Infecção Hospitalar , Fraturas do Quadril , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Pandemias , Infecção Hospitalar/complicações , Infecção Hospitalar/epidemiologia , Mortalidade Hospitalar , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Estudos Retrospectivos
7.
Surgeon ; 20(4): 237-240, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34103268

RESUMO

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) pandemic resulted in major disruption to hip fracture services. This frail patient group requires specialist care, and disruption to services is likely to result in increases in morbidity, mortality and long-term healthcare costs. AIMS: To assess disruption to hip fracture services during the COVID-19 pandemic. METHODS: A questionnaire was designed for completion by a senior clinician or service manager in each participating unit between April-September 2020. The survey was incorporated into existing national-level audits in Germany (n = 71), Scotland (n = 16), and Ireland (n = 16). Responses from a further 82 units in 11 nations were obtained via an online survey. RESULTS: There were 185 units from 14 countries that returned the survey. 102/160 (63.7%) units reported a worsening of overall service quality, which was attributed predominantly to staff redistribution, reallocation of inpatient areas, and reduced access to surgical facilities. There was a high rate of redeployment of staff to other services: two thirds lost specialist orthopaedic nurses, a third lost orthogeriatrics services, and a quarter lost physiotherapists. Reallocation of inpatient areas resulted in patients being managed by non-specialised teams in generic wards, which increased transit of patients and staff between clinical areas. There was reduced operating department access, with 74/160 (46.2%) centres reporting a >50% reduction. Reduced theatre efficiency was reported by 135/160 (84.4%) and was attributed to staff and resource redistribution, longer anaesthetic and transfer times, and delays for preoperative COVID-19 testing and using personal protective equipment (PPE). CONCLUSION: Hip fracture services were disrupted during the COVID-19 pandemic and this may have a sustained impact on health and social care. Protection of hip fracture services is essential to ensure satisfactory outcomes for this vulnerable patient group.


Assuntos
COVID-19 , Fraturas do Quadril , Ortopedia , COVID-19/epidemiologia , Teste para COVID-19 , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Pandemias , Inquéritos e Questionários
8.
Langmuir ; 35(14): 4909-4917, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30817890

RESUMO

Nanoparticles (NPs) functionalized with antibodies on their surface are used in a wide range of research applications. However, the bioconjugation chemistry between the antibodies and the surface of nanoparticles can be very challenging, often accompanied by several undesired effects such as nanoparticle aggregation, antibody denaturation, or poor target recognition of the surface-bound antibodies. Here, we report on a synthesis of fluorescent silica nanoparticle-antibody (NP-Ab) conjugates, in which polycarboxylated dextran is used as the multivalent linker. First, we present a synthetic methodology to prepare polycarboxylated dextrans with molecular weights of 6, 40, and 70 kDa. Second, we used water-soluble, polycarboxylated dextrans as a multivalent spacers/linkers to immobilize antibodies onto fluorescent silica nanoparticles. The prepared NP-Ab conjugates were tested in a direct binding assay format in both phosphate-buffered saline buffer and whole serum to investigate the role of the spacer/linker in the capacity of the NP-Ab to specifically recognize their target in "clean" and also in complex media. We have compared the dextran conjugates with two standards: (a) NP-Ab with antibodies attached on the surface of nanoparticles through the classical physical adsorption method and (b) NP-Ab where an established poly(amidoamine) (PAMAM) dendrimer was used as the linker. Our results showed that the polycarboxylated 6 kDa dextran facilitates antibody immobilization efficiency of nearly 92%. This was directly translated into the improved molecular recognition of the NP-Ab, which was measured by a direct binding assay. The signal-to-noise ratio in buffered solution for the 6 kDa dextran NP-Ab conjugates was 81, nearly 3 times higher than that of PAMAM G4.5 conjugates and 9 times higher than the physically adsorbed NP-Ab sample. In whole serum, the effect of 6 kDa dextran was more hindered due to the formation of protein corona but the signal-to-noise ratio was at least double that of the physically adsorbed NP-Ab conjugates.


Assuntos
Anticorpos/análise , Dextranos/química , Nanopartículas/análise , Fosfatos/química , Solução Salina/química , Soluções Tampão , Dextranos/sangue , Dextranos/síntese química , Corantes Fluorescentes/análise , Tamanho da Partícula , Dióxido de Silício/análise , Propriedades de Superfície
9.
Br J Neurosurg ; 33(5): 495-499, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31008658

RESUMO

Purpose: Neurosurgical patients are often complex and require high quality, attentive care in the immediate postoperative period. We identified a number of issues in our department pertaining to patient safety and the assessment and management of patients following handover of care to the neurosurgical ward, and intervened with an aim to provide safe, timely, patient-centred, and procedure-specific care in the postoperative period. Method: We reviewed the records of 50 patients between (Aug-Oct 2015) and analysed quality of postoperative assessment, prescriptions, and adherence to national standards of postoperative care. We identified barriers to effective practice and intervened by introducing a bespoke Neurosurgical Postoperative Checklist which provided a framework for the assessment and management of patients in the immediate postoperative period. We reviewed the records of 50 patients (Oct-Nov 2016) to assess adherence to the new protocol and its effect on the quality of postoperative care, and reaudited a further 50 patients after one year (Sep-Nov 2016). Results: Prior to intervention 37/50 (74.0%) patients were reviewed postoperatively and quality was poor. This improved to 49/50 (98.0%) post-Checklist and was associated with a dramatic improvement in quality of care compared to pre-Checklist: appropriate analgesia and anti-emetics prescribed in 98.0% and 98.0% versus 26.0% and 18.0%; appropriate antibiotic and corticosteroid prescription in 100.0% and 100.0% versus 26.0% and 18.0%; and timely prescription of an appropriate VTE prophylaxis plan in 98.0% versus 2.0% pre-Checklist. Improvements were sustained after one year. Conclusions: The introduction of our Neurosurgery Postoperative Checklist yielded dramatic improvements in patient safety and quality of postoperative care, as indicated by improved adherence to national standards of postoperative clinical assessment, and the quality and safety of medication prescriptions which are so vital in complex neurosurgical patients. We recommend the use of a neurosurgical Postoperative Checklist as a simple, cheap, reproducible tool to improve patient care.


Assuntos
Lista de Checagem/métodos , Procedimentos Neurocirúrgicos/métodos , Segurança do Paciente , Cuidados Pós-Operatórios/métodos , Qualidade da Assistência à Saúde , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Prescrições de Medicamentos , Fidelidade a Diretrizes , Humanos , Dor Pós-Operatória/tratamento farmacológico , Melhoria de Qualidade
10.
J Mol Recognit ; 31(3)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28791744

RESUMO

The efficiency of the stoichiometric non-covalent imprinting of the imide 2,3,5-tri-O-acetyluridine (TAU) with 2,6-bis(acrylamido)pyridine (BAAPy) as functional monomer due to their strong donor-acceptor-donor/acceptor-donor-acceptor (DAD/ADA) hydrogen bond array interaction has been evaluated by bulk imprinting. This study is the first to investigate the imprinting and template rebinding efficiencies of the TAU/BAAPy molecularly imprinted polymeric (MIP) system prepared by precipitation polymerisation. We found that the stoichiometric 1:1 T:FM ratio has not been maintained in precipitation polymerisation and an optimal TAU:BAAPy ratio of 1:2.5 was obtained in acetonitrile without agitation affording an affinity constant (1.7 × 104 M-1 ) and a binding capacity (3.69 µmol/g) higher than its bulk counterpart. Molecular modelling, NMR studies, and selectivity assays against analogues uridine and 2,3,5-tri-O-acetyl cytidine (TAC) indicate that, aside from the DAD/ADA hydrogen bond interaction, BAAPy also interacts with the acetyl groups of TAU. Template incorporation and rebinding in precipitation MIPs are favoured by a moderate initiator concentration, ie, initiator:total monomer (I:TM) ratio of 1:131, while low I:TM ratio (ie, 1:200) drastically reduced template incorporation and binding capacity. Vigorous agitation by stirring showed higher template incorporation but significantly lower template rebinding compared to that prepared without agitation. While the imprinting efficiencies for the best performing bulk and precipitation TAU MIPs generated in this study were moderate, 41% and 60%, respectively, their rebinding capacities were only between 3 and 4% of the incorporated template. We also present quantitative nuclear magnetic resonance spectroscopy as an efficient method for MIP characterisation.


Assuntos
Substâncias Macromoleculares/química , Impressão Molecular , Polímeros/química , Acetatos/química , Ligação de Hidrogênio , Imidas/síntese química , Imidas/química , Substâncias Macromoleculares/síntese química , Polimerização , Polímeros/síntese química , Piridinas/síntese química , Piridinas/química , Uridina/análogos & derivados , Uridina/química
11.
Chirality ; 30(6): 708-718, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29645307

RESUMO

Circular dichroism (CD) spectroscopy has been used extensively for the investigation of the conformation and configuration of chiral molecules, but its use for evaluating the mode of self-assembly in soft materials has been limited. Herein, we report a protocol for the study of such materials by electronic CD spectroscopy using commercial/benchtop instruments and synchrotron radiation (SR) using the B23 beamline available at Diamond Light Source. The use of the B23 beamtime for SRCD was advantageous because of the unique enhanced spatial resolution achieved because of its highly collimated and small beamlight cross section (ca. 250 µm) and higher photon flux in the far UV region (175-250 nm) enhancing the signal-to-noise ratio relative to benchtop CD instruments. A set of low molecular weight (LMW) hydrogelators, comprising two Fmoc-protected enantiomeric monosaccharides and one Fmoc dipeptide (Fmoc-FF), were studied. The research focused on the optimization of sample preparation and handling, which then enabled the characterization of sample conformational homogeneity and thermal stability. CD spectroscopy, in combination with other spectroscopic techniques and microscopy, will allow a better insight into the self-assembly of chiral building blocks into higher order structural architectures.

13.
Liver Int ; 35(10): 2318-26, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25728498

RESUMO

BACKGROUND & AIMS: Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity. METHODS: The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63). RESULTS: HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04). CONCLUSIONS: Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia.


Assuntos
Ordem de Nascimento , Carcinoma Hepatocelular/epidemiologia , Portador Sadio/epidemiologia , Antígenos de Superfície da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Portador Sadio/virologia , Estudos de Casos e Controles , Feminino , Gâmbia/epidemiologia , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/transmissão , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Risco
14.
J Mol Recognit ; 27(9): 559-65, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25042710

RESUMO

Molecularly imprinted polymers (MIPs) for salicylic acid were synthesized and evaluated in aqueous environments in the aim to apply them as drug delivery carriers. One organic MIP and one inorganic MIP based on the sol-gel process were synthesized. The organic MIP was prepared by radical polymerization using the stoichiometric functional monomer, 1-(4-vinylphenyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea, which can establish strong electrostatic interactions with the -COOH of salicylic acid. The sol-gel MIP was prepared with 3-(aminopropyl)triethoxysilane and trimethoxyphenylsilane, as functional monomers and tetraethyl orthosilicate as the crosslinker. While the organic MIPs bound the target specifically in acetonitrile, they exhibited lower binding in the presence of water, although the imprinting factor increased under these conditions, due to reduced non-specific binding. The sol-gel MIP has a high specificity and capacity for the drug in ethanol, a solvent compatible with drug formulation and biomedical applications. In vitro release profiles of the polymers in water were evaluated, and the results were modelled by Fick's law of diffusion and the power law. Analysis shows that the release mechanism was predominantly diffusion-controlled.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Impressão Molecular , Transição de Fase , Ácido Salicílico/farmacologia , Dióxido de Silício/química , Água/química , Preparações de Ação Retardada , Luz , Microscopia Eletrônica de Varredura , Polímeros/síntese química , Polímeros/química , Espalhamento de Radiação , Temperatura
15.
BMC Infect Dis ; 14: 7, 2014 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-24397793

RESUMO

BACKGROUND: Gambian infants were not routinely vaccinated against hepatitis B virus (HBV) before 1986. During 1986-90 the Gambia Hepatitis Intervention Study (GHIS) allocated 125,000 infants, by area, to vaccination or not and thereafter all infants were offered the vaccine through the nationwide immunisation programme. We report HBV serology from samples of GHIS vaccinees and unvaccinated controls, and from children born later. METHODS: During 2007-08, 2670 young adults born during the GHIS (1986-90) were recruited from 80 randomly selected villages and four townships. Only 28% (753/2670) could be definitively linked to their infant HBV vaccination records (255 fully vaccinated, 23 partially vaccinated [1-2 doses], 475 not vaccinated). All were tested for current HBV infection (HBV surface antigen [HBsAg]) and, if HBsAg-negative, evidence of past infection (HBV core-protein antibody [anti-HBc]). HBsAg-positive samples (each with two age- and sex-matched HBsAg-negative samples) underwent liver function tests. In addition, 4613 children born since nationwide vaccination (in 1990-2007) were tested for HBsAg. Statistical analyses ignore clustering. RESULTS: Comparing fully vaccinated vs unvaccinated GHIS participants, current HBV infection was 0.8% (2/255) vs 12.4% (59/475), p < 0.0001, suggesting 94% (95% CI 77-99%) vaccine efficacy. Among unvaccinated individuals, the prevalence was higher in males (p = 0.015) and in rural areas (p = 0.009), but adjustment for this did not affect estimated vaccine efficacy. Comparing fully vaccinated vs unvaccinated participants, anti-HBc was 27.4% (70/255) vs 56.0% (267/475), p < 0.00001. Chronic active hepatitis was not common: the proportion of HBsAg-positive subjects with abnormal liver function tests (ALT > 2 ULN) was 4.1%, compared with 0.2% in those HBsAg-negative. The prevalence of antibodies to hepatitis C virus was low (0.5%, 13/2592). In children born after the end of GHIS, HBsAg prevalence has remained low; 1.4% (15/1103) in those born between 1990-97, and 0.3% (9/35150) in those born between 1998-2007. CONCLUSIONS: Infant HBV vaccination achieves substantial protection against chronic carriage in early adulthood, even though approximately a quarter of vaccinated young adults have been infected. This protection persists past the potential onset of sexual activity, reinforcing previous GHIS findings of protection during childhood and suggesting no need for a booster dose. Nationwide infant HBV vaccination is controlling chronic infection remarkably effectively.


Assuntos
Vacinas contra Hepatite B , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Programas de Imunização , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Crônica , Doenças Transmissíveis , Estudos Transversais , Feminino , Gâmbia/epidemiologia , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite Crônica/epidemiologia , Humanos , Lactente , Masculino , Parto , Prevalência , Resultado do Tratamento , Vacinação , Adulto Jovem
16.
Anal Bioanal Chem ; 406(25): 6275-84, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25080025

RESUMO

In this paper, we describe the synthesis and evaluation of molecularly imprinted polymers (MIPs), prepared using 2',3',5'-tri-O-acyluridines as 'dummy' templates, for the selective recognition of uridine nucleosides. The MIPs were synthesised using a non-covalent approach with 2,6-bis-acrylamidopyridine (BAAPy) acting as the binding monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent. The MIPs were evaluated in terms of capacity, selectivity and specificity by analytical and frontal liquid chromatography measurements. The results obtained in organic mobile phases suggest that the nucleosides are specifically bound to the polymer by the complementary hydrogen bonding motifs of the binding monomer and the nucleoside bases. The MIPs exhibited relatively high imprinting factors for 2',3',5'-tri-O-acyluridines, while they did not show any binding capacity for other nucleosides lacking the imide moiety on their base. Moreover, the presence of ester-COO groups in the EGDMA cross-linker may lead to the formation of additional hydrogen bonds with the 2',3' and/or 5'-OH of sugar part, allowing enhancement of the recognition of the uridine nucleosides. In aqueous media, results show that the binding is driven by hydrophobic interactions.


Assuntos
Polímeros/química , Uridina/química , Ligação de Hidrogênio , Impressão Molecular , Polímeros/síntese química , Estereoisomerismo
17.
Int J Cancer ; 132(3): 658-65, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22618962

RESUMO

The Gambia National Cancer Registry (GNCR) is one of the few nationwide population-based cancer registries in sub-Saharan Africa. Most registries in sub-Saharan Africa are limited to cities; therefore, the GNCR is important in providing estimates of cancer incidence in rural Africa. Our study assesses the quality of its data. The methods proposed by Bray and Parkin, and Parkin and Bray (Eur J Cancer 2009;45:747-64) were applied to the registry data from 1990 to 2009 to assess comparability, validity and completeness. The system used for classification and coding of neoplasms followed international standards. The percentage of cases morphologically verified was 18.1% for men and 33.1% for women, and that of death certificate only cases was 6.6 and 3.6%, respectively. Incidence rates in rural regions were lower than in the urban part of the country, except amongst young male adults. Comparison with other West African registries showed that the incidences of liver and uterine cervical cancer were comparable, but those of prostate and breast in The Gambia were relatively low. The overall completeness was estimated at 50.3% using the capture-recapture method. The GNCR applies international standard practices to data collection and handling, providing valuable data on cancer incidence in sub-Saharan Africa. However, the data are incomplete in the rural and elderly populations probably because of health care access and use.


Assuntos
Neoplasias/epidemiologia , Sistema de Registros/normas , Coleta de Dados , Feminino , Gâmbia/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , Sistemas de Informação , Masculino , Gradação de Tumores , Sistema de Registros/estatística & dados numéricos , População Rural
18.
Am J Geriatr Psychiatry ; 21(12): 1173-89, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23907068

RESUMO

Delirium is a serious and common acute neuropsychiatric syndrome that is associated with short- and long-term adverse health outcomes. However, relatively little delirium research has been conducted in unselected populations. Epidemiologic research in such populations has the potential to resolve several questions of clinical significance in delirium. Part 1 of this article explores the importance of population selection, case-ascertainment, attrition, and confounding. Part 2 examines a specific question in delirium epidemiology: What is the relationship between delirium and trajectories of cognitive decline? This section assesses previous work through two systematic reviews and proposes a design for investigating delirium in the context of longitudinal cohort studies. Such a design requires robust links between community and hospital settings. Practical considerations for case-ascertainment in the hospital, as well as the necessary quality control of these programs, are outlined. We argue that attention to these factors is important if delirium research is to benefit fully from a population perspective.


Assuntos
Transtornos Cognitivos/epidemiologia , Coleta de Dados/métodos , Delírio/epidemiologia , Projetos de Pesquisa , Delírio/diagnóstico , Progressão da Doença , Humanos
19.
Arthritis Rheum ; 64(5): 1673-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22143958

RESUMO

OBJECTIVE: Little is known about Legg-Calvé-Perthes disease, a common childhood precursor to osteoarthritis of the hip. This study was undertaken to analyze the incidence of Legg-Calvé-Perthes disease in the UK, with respect to geographic and temporal trends over a 19-year period. METHODS: The General Practice Research database was analyzed to identify incident cases between 1990 and 2008 in children ages 0-14 years. Incidence rates were calculated by year and by region (National Health Service Strategic Health Authority regions in England, and Scotland, Wales, and Northern Ireland), and the association with regional markers of deprivation examined. RESULTS: Over the 19-year period there was a dramatic decline in Legg-Calvé-Perthes disease incidence, with annual rates among children 0-14 years old declining from 12.2 per 100,000 to 5.7 per 100,000 (P < 0.001). There was also marked geographic variation, with incidence rates in Scotland more than twice those in London (10.39 [95% confidence interval 8.05-13.2] versus 4.6 [95% confidence interval 3.4-6.1] per 100,000 0-14-year-olds). A more rapid decline in incidence was apparent in the Northern regions compared to Southern regions. The quintile with the highest degree of deprivation had the highest disease incidence (rate ratio 1.49 [95% confidence interval 1.10-2.04]) and, with the exception of London, regional incidence showed a strong linear relationship with regional deprivation score (P < 0.01). CONCLUSION: The incidence of Legg-Calvé-Perthes disease in the UK has a strong North-South divide, with a greater disease incidence within the Northern regions of the UK. There was a marked decline in incidence over the study period, which was more marked in Northern areas. The declining incidence, along with the geographic variation, suggests that a major etiologic determinant in Legg-Calvé-Perthes disease is environmental and closely linked to childhood deprivation.


Assuntos
Doença de Legg-Calve-Perthes/epidemiologia , Áreas de Pobreza , Carência Psicossocial , Adolescente , Criança , Desenvolvimento Infantil , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Incidência , Doença de Legg-Calve-Perthes/etiologia , Masculino , Sistema de Registros , Fatores de Risco , Reino Unido/epidemiologia
20.
J Pediatr Orthop ; 33(6): 644-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23812131

RESUMO

BACKGROUND: Legg-Calve-Perthes Disease (LCPD) is a childhood precursor to hip osteoarthritis, for which the etiology is unknown. There is a widespread belief that affected individuals are "hyperactive," propagating a theory that such children may have sustained an epiphyseal injury that precipitated the onset of LCPD. This study seeks to quantify the association with hyperactivity, and the wider psychological burden of the disease. METHODS: A case-control study was conducted among 146 cases of LCPD and 142 hospital controls, frequency matched by age and sex. Psychological domains were measured using the Strength and Difficulties Questionnaire. Adjustment was made for age, sex, and socioeconomic deprivation. Results were stratified by the time elapsed since LCPD was diagnosed. RESULTS: Significant associations (P<0.05) existed with the majority of the psychological domains captured by the Strength and Difficulties Questionnaire [odds ratio (OR) for "high" level of difficulties-Emotion OR 3.2, Conduct OR 2.1, Inattention-Hyperactivity OR 2.7, Prosocial Behavior OR 1.9]. Hyperactivity was especially marked among individuals within 2 years of diagnosis (OR 8.6; P<0.001), but not so among individuals over 4 years from diagnosis. Emotional symptoms persisted long after resolution of the active phase of disease. CONCLUSIONS: There was a marked psychological burden among individuals with LCPD, which was most marked amongst individuals with a recent diagnosis. The breadth and inferred temporality of these disturbances may be a function of the disease process, through restriction of activities and disability, or may be a fundamental disease characteristic related directly to disease or to its etiological determinant.


Assuntos
Hipercinese/epidemiologia , Doença de Legg-Calve-Perthes/psicologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Hipercinese/etiologia , Doença de Legg-Calve-Perthes/fisiopatologia , Masculino , Inquéritos e Questionários , Fatores de Tempo
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