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1.
Eur J Cancer Care (Engl) ; 27(2): e12720, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28597493

RESUMO

Many individuals affected by cancer who experience emotional distress report not wanting help. This review aims to understand why individuals affected by cancer seek, accept or decline help for emotional distress and what influences these actions. A systematic review and thematic synthesis of the qualitative literature was conducted. Using pre-defined search terms, four electronic databases were searched from January 2000 to May 2016. Pre-determined inclusion and exclusion criteria were then applied. Identified papers were quality appraised. In total, 32 papers were included in the synthesis. Four themes emerged from data synthesis: attaining normality-the normality paradox; being emotionally literate; perceptions of help; needs-support gap. Attaining normality is ideographic, context dependent and temporally situated; some individuals maintain normality by not seeking/declining help whereas others seek/accept help to achieve a new normality. Thus, attaining normality paradoxically functions to explain both why individuals sought/accepted help or did not seek/declined help. Data indicate that a context dependent, systems thinking approach is merited to enhance psychosocial care. In particular, clinicians must actively explore the personal context of an individual's distress to ensure that help desired and help offered are mutually understood. Further research must address the limitations of the current evidence base to advance theoretical understanding.


Assuntos
Neoplasias/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Estresse Psicológico/terapia , Necessidades e Demandas de Serviços de Saúde , Humanos , Pesquisa Qualitativa
2.
J Antimicrob Chemother ; 70(6): 1798-803, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25759035

RESUMO

BACKGROUND: Current guidelines for dosing of anti-TB drugs in children advocate higher doses for rifampicin and isoniazid despite limited availability of paediatric data on the pharmacokinetics of these drugs, especially from Africa, where the burden of childhood disease remains high. METHODS: Thirty children aged 6 months to 15 years underwent intensive pharmacokinetic sampling for first-line anti-TB drugs at Queen Elizabeth Central Hospital, Blantyre, Malawi. Rifampicin, isoniazid, pyrazinamide and ethambutol were dosed at 10, 5, 25 and 20 mg/kg, respectively. Plasma drug concentrations were determined using sensitive, validated bioanalytical methods and summary pharmacokinetic parameters were estimated using non-compartmental analysis. RESULTS: The median (IQR) Cmax was 2.90 (2.08-3.43), 3.37 (2.55-4.59), 34.60 (32.30-40.90) and 1.20 (0.85-1.68) mg/L while the median (IQR) AUC0-∞ was 16.92 (11.10-22.74), 11.48 (7.35-18.93), 333.50 (279.50-487.2) and 8.65 (5.96-11.47) mg·h/L for rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. For all drugs, pharmacokinetic parameters relating to drug absorption and exposure were lower than those published for adults, though similar to existing paediatric data from sub-Saharan Africa. Weight and/or dose predicted at least one measure of exposure for all drugs. Age-related decreases in CL/F for rifampicin and pyrazinamide and a biphasic elimination pattern of isoniazid were observed. Predicted AUC0 -∞ for rifampicin dosed at 15 mg/kg was comparable to that of adults while the dose required to achieve ethambutol exposure similar to that in adults was 55 mg/kg or higher. CONCLUSIONS: These data support recently revised WHO recommendations for dosing of anti-TB drugs in children, but dosing of ethambutol in children also appears inadequate by comparison with adult pharmacokinetic data.


Assuntos
Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Etambutol/administração & dosagem , Etambutol/farmacocinética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Isoniazida/administração & dosagem , Isoniazida/farmacocinética , Malaui , Masculino , Plasma/química , Pirazinamida/administração & dosagem , Pirazinamida/farmacocinética , Rifampina/administração & dosagem , Rifampina/farmacocinética
3.
Drug Discov Today Technol ; 10(3): e359-64, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24050132

RESUMO

Identifying the most effective new drugs for tuberculosis will depend on developing systems for preclinical testing that better reflect conditions in the diseased host and the characteristics of persistent M tuberculosis. Integrating information from these diverse new technologies using a model-based approach to antituberculosis drug development could facilitate more effective use of this information in transitioning novel compounds successfully to the clinical phase.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/uso terapêutico , Humanos
4.
ACS ES T Water ; 2(4): 527-538, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35403122

RESUMO

The COVID-19 pandemic has increased the worldwide production and use of disposable plastic face masks (DPFMs). The release of micro- and nanopollutants into the environment is one of the impacts derived from regulated and unregulated disposal of DPFMs. This study focuses on the emission of pollutants from medical-grade DPFMs when submerged in deionized water, simulating regulated and unregulated disposal of these masks. Three brands of FFP2 and three brands of Type IIR medical masks, produced in various countries (UK, EU, and non-EU), were investigated. Field emission gun scanning electron microscopy (FEG-SEM) was used to obtain high-resolution images of the micro- and nanoparticles, and 0.02 µm pore size inorganic membranes were used to retain and subsequently analyze smaller particle size nanoparticles (>20 nm) released from the DPFMs. Particles and fibers in the micro- and nanoscale were found in all six DPFM brands. SEM with energy-dispersive spectroscopy analysis revealed the presence of particles containing different heavy metals like lead, mercury, and arsenic. Inductively coupled plasma mass spectrometry analysis confirmed the leaching of trace heavy metals to water (antimony up to 2.41 µg/L and copper up to 4.68 µg/L). Liquid chromatography-mass spectrometry analysis identified polar organic species related to plastic additives and contaminants such as polyamide-66 monomers and oligomers.

5.
Int J Tuberc Lung Dis ; 23(5): 606-611, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31097070

RESUMO

SETTING A free, national smoking cessation service for adults based on behavioural and pharmaceutical support in Wales, UK. OBJECTIVE To establish whether the Fagerström score at the assessment session could be used to predict subsequent treatment attendance. Non-attendance affects the individual's health and the efficiency of the service. DESIGN Anonymised data from 39 967 Stop Smoking Wales assessment session attendees were assessed using logistic regression. The outcome variable was subsequent attendance/non-attendance for at least one treatment session. Fagerström scores were grouped into 'very low' (0-2), 'low' (3-4), 'medium' (5) and 'high' (6-10). RESULTS People with medium (OR 1.15, 95%CI 1.08-1.24) or low Fagerström scores (OR 1.07, 95%CI 1.00-1.14) were more likely to attend treatment sessions than people with very low (OR 1.03, 95%CI 0.94-1.12) or high (baseline) Fagerström scores. The final model comprised nine other statistically significant covariates: current age, sex, residential deprivation level, number of previous quit attempts, type of appointment (group or one-to-one), time of appointment, appointment season, time spent waiting for an appointment and distance from home to the clinic. CONCLUSION The Fagerström score at the assessment session could be used to identify smokers at an increased risk of not attending subsequent treatment. Further research is required to evaluate the impact of targeting those with the highest and lowest Fagerström scores at the assessment session upon treatment attendance. .


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fumantes/estatística & dados numéricos , Abandono do Hábito de Fumar/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Cooperação do Paciente/estatística & dados numéricos , País de Gales
6.
Sci Justice ; 59(3): 322-331, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31054821

RESUMO

Human provenance studies employing isotopic analysis have become an essential tool in forensic and archaeological sciences, with multi-isotope approaches providing more specific location estimates compared to single isotope studies. This study reports on the human provenancing capability of neodymium isotopes (143Nd/144Nd), a relatively conservative tracer in the environment. Neodymium isotope ratios have only recently been determined on human remains due to low concentrations in human dental enamel (ppb range), requiring thermal ionisation mass spectrometry (TIMS) using 1013â€¯Ω resistors. Dental elements (third molars) from 20 individuals born and raised in the Netherlands were analysed for Nd concentration (n = 12) and Nd isotope ratios (n = 15). The geological control on Nd isotope composition was examined using coupled Nd-Sr isotope analysis of the same third molar. Teeth from different geological environments were also analysed (Caribbean, Columbian, and Icelandic, n = 5). Neodymium elemental concentrations in dental elements ranged between 0.1 and 7.9 ppb (median 0.5 ppb). The Dutch 143Nd/144Nd ratios of the provinces of Limburg and Friesland were between 0.5118 and 0.5121, with Dutch 87Sr/86Sr ratios in agreement with the previously established local range (0.708-0.710). The current findings were compared to previously published results on Nd concentration and composition from Dutch individuals. The concentration of Nd and 143Nd/144Nd ratios were weakly correlated (R2 = 0.47, n = 17) in Dutch human dental enamel. The majority (n = 25, 83.3%) of individuals had Nd and Sr isotope values isotopically indistinguishable from the geological environment in which their third molars formed and mineralised. However, the Nd isotope ratios of the Icelandic individual and several Dutch individuals (n = 4) suggested that Nd in enamel is not solely influenced by geological environment. In order for neodymium isotopes to be quantitatively applied in forensic and archaeological settings further analyses of individuals from various geographical regions with well-defined dietary Nd isotope data are required.


Assuntos
Esmalte Dentário/química , Isótopos/análise , Espectrometria de Massas , Dente Serotino/química , Neodímio/análise , Radioisótopos/análise , Adolescente , Região do Caribe , Criança , Colômbia , Dieta , Impedância Elétrica , Odontologia Legal/métodos , Humanos , Islândia , Países Baixos , Dinâmica Populacional , Isótopos de Estrôncio/análise
7.
Int J Tuberc Lung Dis ; 12(2): 128-38, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18230244

RESUMO

SETTING: Current treatment for pulmonary tuberculosis (TB) might be shortened by the incorporation of fluoroquinolones (FQs). OBJECTIVES: A Phase II study aimed to assess the sterilising activities of three novel regimens containing FQs before a Phase III trial of a 4-month regimen containing gatifloxacin (GFX). DESIGN: A total of 217 newly diagnosed smear-positive patients were randomly allocated to one of four regimens: isoniazid (INH), pyrazinamide and rifampicin (RMP) with either ethambutol, GFX, moxifloxacin (MFX) or ofloxacin (OFX) for 2 months. At the end of the study, RMP and INH were given for 4 months. The rates of elimination of Mycobacterium tuberculosis were compared in the regimens using non-linear mixed effects modelling of the serial sputum colony counts (SSCC) during the first 8 weeks. RESULTS: After adjustment for covariates, MFX substitution appeared superior during the early phase of a bi-exponential fall in colony counts, but significant and similar acceleration of bacillary elimination during the late phase occurred with both GFX and MFX (P = 0.002). Substitution of OFX had no effect. These findings were supported by estimates of time to conversion, using Cox regression, but there were no significant differences in proportions culture-negative at 8 weeks. CONCLUSIONS: GFX and MFX improve the sterilising activity of regimens and might shorten treatment; their progression into Phase III trials therefore seems warranted.


Assuntos
Antibacterianos/uso terapêutico , Antituberculosos/uso terapêutico , Compostos Aza/uso terapêutico , Fluoroquinolonas/uso terapêutico , Ofloxacino/uso terapêutico , Quinolinas/uso terapêutico , Adolescente , Adulto , Idoso , Contagem de Colônia Microbiana , Quimioterapia Combinada , Feminino , Gatifloxacina , Humanos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Dinâmica não Linear , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Escarro/microbiologia
8.
Anal Bioanal Chem ; 390(2): 465-76, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18080118

RESUMO

This paper reviews the problems encountered in eleven studies of Sr isotope analysis using laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICPMS) in the period 1995-2006. This technique has been shown to have great potential, but the accuracy and precision are limited by: (1) large instrumental mass discrimination, (2) laser-induced isotopic and elemental fractionations and (3) molecular interferences. The most important isobaric interferences are Kr and Rb, whereas Ca dimer/argides and doubly charged rare earth elements (REE) are limited to sample materials which contain substantial amounts of these elements. With modern laser (193 nm) and MC-ICPMS equipment, minerals with >500 ppm Sr content can be analysed with a precision of better than 100 ppm and a spatial resolution (spot size) of approximately 100 microm. The LA MC-ICPMS analysis of 87Sr/86Sr of both carbonate material and plagioclase is successful in all reported studies, although the higher 84Sr/86Sr ratios do suggest in some cases an influence of Ca dimer and/or argides. High Rb/Sr (>0.01) materials have been successfully analysed by carefully measuring the 85Rb/87Rb in standard material and by applying the standard-sample bracketing method for accurate Rb corrections. However, published LA-MC-ICPMS data on clinopyroxene, apatite and sphene records differences when compared with 87Sr/86Sr measured by thermal ionisation mass spectrometry (TIMS) and solution MC-ICPMS. This suggests that further studies are required to ensure that the most optimal correction methods are applied for all isobaric interferences.

9.
J Neurol Neurosurg Psychiatry ; 77(9): 1036-9, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16793860

RESUMO

BACKGROUND AND OBJECTIVE: The onset of multiple sclerosis is relapsing remitting or primary progressive. An improved understanding of the causes of early progressive disability in primary progressive multiple sclerosis (PPMS) could provide mechanistic targets for therapeutic intervention. METHODS: Five magnetic resonance imaging (MRI) parameters that could potentially cause progressive disability were investigated in 43 patients with early PPMS and in 37 patients with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both grey matter and white matter; intrinsic abnormality in brain, both grey matter and white matter (measured by the magnetisation transfer ratio (MTR)); and atrophy of the upper cervical spinal cord. Both groups were also compared with controls. RESULTS: Patients with PPMS were older and more likely to be men. Both patient groups had atrophy of brain grey matter and white matter, and intrinsic abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2; controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of all five MRI parameters, age and sex. CONCLUSION: Grey matter and white matter of the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant in PPMS treatment trials.


Assuntos
Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Medula Espinal/patologia , Adulto , Idoso , Atrofia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva
10.
Int J Tuberc Lung Dis ; 10(9): 1023-9, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16964795

RESUMO

SETTING: Various methods have been used to estimate the prevalence of Mycobacterium tuberculosis infection from tuberculin survey data. All are complicated by prior sensitisation to environmental mycobacteria and bacille Calmette-Guérin (BCG) vaccination. Mixture analysis has recently been proposed as a means of overcoming misclassification and improving infection prevalence estimates. OBJECTIVE: To compare conventional and mixture model estimates of M. tuberculosis infection prevalence. DESIGN: Mixture models with two or three univariate normal components were fitted to the results of 53 909 tuberculin tests conducted in northern Malawi during 1980-1984. Data were stratified by BCG status, sex and age and corrected for digit preference. Prevalence estimates derived from mixture models were compared with those of conventional methods. RESULTS: The optimal model was age-dependent, with three- and one-component solutions preferred in younger and older age groups, respectively. In contrast with findings from elsewhere, a component corresponding to BCG vaccination was indistinguishable from that attributable to environmental mycobacterial exposure, and infection prevalence estimates in younger individuals with a BCG scar were inflated, irrespective of the method used. CONCLUSION: The validity of infection prevalence and incidence estimates based on mixture modelling is probably locale-dependent, and the assumptions underlying mixture models may not realistically reflect underlying immunological processes.


Assuntos
Teste Tuberculínico/estatística & dados numéricos , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Teste Tuberculínico/métodos
11.
Int J Tuberc Lung Dis ; 20(12): 13-17, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28240567

RESUMO

Predicting the required duration of treatment necessary to yield an acceptable risk of recurrence is a key question facing Phase III trials in both drug-susceptible (DS) and multidrug-resistant tuberculosis (MDR-TB). Data on treatment duration from animal models are increasingly a focus of such studies, but they have not been calibrated against human clinical trials and are lacking in MDR-TB. Empirical meta-regression models based on clinical trials in DS-TB suggest that early bacteriological results and treatment duration may have value in predicting relapse, and have been prospectively validated against the results of three large randomised controlled trials in DS-TB. While few trials have been conducted in MDR-TB to date, and observational cohort data should be interpreted carefully due to bias and confounding, these models also appeared to perform well in two recent cohort studies of MDR-TB. Applying these insights in practice may require innovations in clinical trial design, such as more extensive selection, adaptation and use of multiple durations during Phases II and III. While several studies have identified important individual level prognostic variables that could improve the accuracy of relapse prediction, attempts to stratify treatment duration for individual patients based on these factors have so far met with limited success.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/prevenção & controle , Protocolos Clínicos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Coortes , Pesquisa Empírica , Humanos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva
12.
Int J Tuberc Lung Dis ; 20(8): 1004-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27393531

RESUMO

The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert(®) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.


Assuntos
Antituberculosos/uso terapêutico , Testes Diagnósticos de Rotina/normas , Monitoramento de Medicamentos/normas , Técnicas de Diagnóstico Molecular/normas , Kit de Reagentes para Diagnóstico/normas , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Humanos , Valor Preditivo dos Testes , Avaliação de Programas e Projetos de Saúde , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Tuberculose/epidemiologia , Tuberculose/transmissão
13.
Thromb Res ; 143: 130-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27240111

RESUMO

BACKGROUND: Exercise is well established to lead to exercise-induced hypercoagulability, as demonstrated by kinetic coagulation markers. It remains unclear as to whether exercise-induces changes lead in clot development and increased polymerisation. Fractal dimension (df) has been shown to act as a marker of clot microstructure and mechanical properties, and may provide a more meaningful method of determining the relationship between exercise-induced hypercoagulability and potential clot development. METHODS: df was measured in 24 healthy individuals prior to, after 5min of submaximal exercise, following maximal exercise, 45min of passive recovery and following 60min of recovery. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. RESULTS: Significantly increased df was observed following exercise, returning to resting values following 60min of recovery. The relationship between df and mature clot microstructure was confirmed by SEM: higher df was associated with dense clots formed of smaller fibrin fibres immediately following exercise compared to at rest. Conventional markers of coagulation confirmed findings of previous studies. CONCLUSION: This study demonstrates that df is a sensitive technique which quantifies the structure and properties of blood clots following exercise. In healthy individuals, the haemostatic balance between coagulation and fibrinolysis is maintained in equilibrium following exercise. In individuals with underlying vascular damage who participate in exercise, this equilibrium may be displaced and lead to enhanced clot formation and a prothrombotic state. df may therefore have the potential to not only quantify hypercoagulability, but may also be useful in screening these individuals.


Assuntos
Coagulação Sanguínea , Exercício Físico , Adulto , Testes de Coagulação Sanguínea , Feminino , Fibrina/ultraestrutura , Frequência Cardíaca , Humanos , Masculino , Trombofilia/sangue , Trombofilia/diagnóstico , Adulto Jovem
14.
Nat Commun ; 7: 11201, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-27062914

RESUMO

Simulations predict that hot super-Earth sized exoplanets can have their envelopes stripped by photoevaporation, which would present itself as a lack of these exoplanets. However, this absence in the exoplanet population has escaped a firm detection. Here we demonstrate, using asteroseismology on a sample of exoplanets and exoplanet candidates observed during the Kepler mission that, while there is an abundance of super-Earth sized exoplanets with low incident fluxes, none are found with high incident fluxes. We do not find any exoplanets with radii between 2.2 and 3.8 Earth radii with incident flux above 650 times the incident flux on Earth. This gap in the population of exoplanets is explained by evaporation of volatile elements and thus supports the predictions. The confirmation of a hot-super-Earth desert caused by evaporation will add an important constraint on simulations of planetary systems, since they must be able to reproduce the dearth of close-in super-Earths.

15.
J Neurol ; 252(9): 1037-44, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15834645

RESUMO

Abnormalities within normal-appearing grey and white matter (NAGM and NAWM) occur early in the clinical course of multiple sclerosis (MS) and can be detected in-vivo using the magnetisation transfer ratio (MTR). To better characterize the rates of change in both tissues and to ascertain when such changes begin, we serially studied a cohort of minimally disabled, early relapsing-remitting MS patients, using NAGM and NAWM MTR histograms. Twenty-three patients with clinically definite early relapsing-remitting MS (mean disease duration at baseline 1.9 years), and 19 healthy controls were studied. A magnetisation transfer imaging sequence was acquired yearly for two years. Twenty-one patients and 10 controls completed followup. NAWM and NAGM MTR histograms were derived and mean MTR calculated. A hierarchical regression analysis, adjusting for brain parenchymal fraction,was used to assess MTR change over time. MS NAWM and NAGM MTR were significantly reduced in comparison with controls at baseline and, in patients, both measures decreased further during follow-up: (-0.10 pu/year, p=0.001 and -0.18 pu/year, p<0.001 respectively). The rate of MTR decrease was significantly greater in NAGM than NAWM (p=0.004). Under the assumption that such changes are linear, backward extrapolation of the observed rates of change suggested that NAWM abnormality began before symptom onset. We conclude that increasing MTR abnormalities in NAWM and NAGM are observed early in the course of relapsing-remitting MS. It is now important to investigate whether these measures are predictive of future disability, and consequently, whether MTR could be used as a surrogate marker in therapeutic trials.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiografia
16.
Aust Dent J ; 50(1): 6-15; quiz 56, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15881300

RESUMO

This article is a review of the recent literature pertaining to the oral sequelae of eating disorders (EDs). Dentists are recognized as being some of the first health care professionals to whom a previously undiagnosed eating disorder patient (EDP) may present. However, despite the prevalence (up to 4 per cent) of such conditions in teenage girls and young adult females, there is relatively little published in the recent literature regarding the oral sequelae of EDs. This compares unfavourably with the attention given recently in the dental literature to conditions such as diabetes mellitus, which have a similar prevalence in the adult population. The incidence of EDs is increasing and it would be expected that dentists who treat patients in the affected age groups would encounter more individuals exhibiting EDs. Most of the reports in the literature concentrate on the obvious clinical features of dental destruction (perimolysis), parotid swelling and biochemical abnormalities particularly related to salivary and pancreatic amylase. However, there is no consistency in explanation of the oral phenomena and epiphenomena seen in EDs. Many EDPs are nutritionally challenged; there is a relative lack of information pertaining to non-dental, oral lesions associated with nutritional deficiencies.


Assuntos
Cárie Dentária/etiologia , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Doenças da Boca/etiologia , Erosão Dentária/etiologia , Adolescente , Adulto , Perda do Osso Alveolar/etiologia , Transtornos de Deglutição/etiologia , Feminino , Humanos , Doenças Periodontais/etiologia , Doenças das Glândulas Salivares/etiologia , Distúrbios do Paladar/etiologia
17.
Int J Tuberc Lung Dis ; 19(6): 626-34, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25946350

RESUMO

Drug development for tuberculosis (TB) faces numerous practical obstacles, including the need for combination treatment with at least three drugs, reliance on possibly unrepresentative animal models which may not reproduce key features of human disease and the lack of a well-validated surrogate endpoint for stable cure. Pivotal Phase III trials are large, lengthy and expensive, and the funding and capacity to conduct them are limited worldwide. More rational methods for the selection of priority regimens for Phase III are urgently needed to avoid costly late-stage failures. We examine the suitability of adaptive clinical trial designs for drug development in TB, focusing on designs for Phase IIB and III trials, where we believe the biggest gains in efficiency can be made. Key areas that may be addressed by such designs are improvements in the selection of doses and combinations of drugs in early clinical development and in maximising the power of confirmatory trials in multidrug-resistant TB, where patient numbers and complexity pose practical limitations. We encourage trialists and regulators in this area to consider the advantages that may be offered by these designs and their potential to more effectively and rapidly identify better treatment regimens for TB patients worldwide.


Assuntos
Antituberculosos/uso terapêutico , Ensaios Clínicos Fase II como Assunto/métodos , Descoberta de Drogas/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Tuberculose/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/métodos , Interpretação Estatística de Dados , Descoberta de Drogas/estatística & dados numéricos , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
19.
Sci Total Environ ; 506-507: 149-63, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25460949

RESUMO

In human risk assessment, ingestion of soil is considered a major route of toxic Pb exposure. A large body of research has focussed on the measurement of the 'total' Pb contents in sediment, soil and dust as a measure for the exposure to lead. We report that Pb bioaccessibility (i.e. the maximum bioavailability), determined with an in vitro test, does not necessarily depend on the total Pb content. In contrast, the Pb bioaccessibility is initially controlled by the chemical form and particle size of the Pb source, which in turn determine its solubility. Furthermore, when anthropogenic Pb resides within the soil, it may form new, more stable, minerals and/or binds to organic matter, clay, reactive iron or other reactive phases, changing its bioaccessibility. The bioaccessible Pb fraction of 28 soils, polluted with various Pb sources (including residues of Pb bullets and pellets, car battery Pb, city waste and diffuse Pb), was determined with an in vitro-test and varied from 0.5% to 79.0% of total Pb. The highest Pb bioaccessibility (60.7% to 79.0%) was measured in soils polluted with residues of Pb bullets and pellets (shooting range), while the lowest Pb bioaccessibility (0.5%-8.3%) was measured in soils polluted with city waste (including remnants of Pb glazed potsherds and rooftiles, Pb based paint flakes, and Pb sheets). Bioaccessibility of Pb was correlated with pH, organic matter and reactive Fe. These results indicate that soil characteristics play an important role in the oral bioaccessibility of lead in polluted soils. Instead of basing human risk assessment solely on total Pb contents we propose to incorporate in vitro bioaccessibility tests, taking factors such as soil pH, organic matter content and reactive iron content into account. This approach will result in a better insight into the actual risks of Pb polluted soils to children.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluição Ambiental/estatística & dados numéricos , Chumbo/análise , Poluentes do Solo/análise , Humanos , Solo/química
20.
Int J Tuberc Lung Dis ; 19(8): 904-11, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26162355

RESUMO

SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to anti-tuberculosis treatment. OBJECTIVES: To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS: The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti-tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS: Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/efeitos adversos , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Longitudinais , Malaui/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Tuberculose Pulmonar/sangue , Vitamina D/sangue , Deficiência de Vitamina D/etiologia
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