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1.
Nature ; 583(7815): 211-214, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641814

RESUMO

The discovery of a radioactively powered kilonova associated with the binary neutron-star merger GW170817 remains the only confirmed electromagnetic counterpart to a gravitational-wave event1,2. Observations of the late-time electromagnetic emission, however, do not agree with the expectations from standard neutron-star merger models. Although the large measured ejecta mass3,4 could be explained by a progenitor system that is asymmetric in terms of the stellar component masses (that is, with a mass ratio q of 0.7 to 0.8)5, the known Galactic population of merging double neutron-star systems (that is, those that will coalesce within billions of years or less) has until now consisted only of nearly equal-mass (q > 0.9) binaries6. The pulsar PSR J1913+1102 is a double system in a five-hour, low-eccentricity (0.09) orbit, with an orbital separation of 1.8 solar radii7, and the two neutron stars are predicted to coalesce in [Formula: see text] million years owing to gravitational-wave emission. Here we report that the masses of the pulsar and the companion neutron star, as measured by a dedicated pulsar timing campaign, are 1.62 ± 0.03 and 1.27 ± 0.03 solar masses, respectively. With a measured mass ratio of q = 0.78 ± 0.03, this is the most asymmetric merging system reported so far. On the basis of this detection, our population synthesis analysis implies that such asymmetric binaries represent between 2 and 30 per cent (90 per cent confidence) of the total population of merging binaries. The coalescence of a member of this population offers a possible explanation for the anomalous properties of GW170817, including the observed kilonova emission from that event.

2.
Environ Health ; 22(1): 51, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415220

RESUMO

INTRODUCTION: Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI. METHODS: Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria. RESULTS: Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07-3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23-3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12-7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56-6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07-5.62], p ≤ 0.05) among those who met the GWI case criteria. CONCLUSION: These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population.


Assuntos
Apolipoproteínas E , Síndrome do Golfo Pérsico , Síndrome do Golfo Pérsico/genética , Humanos , Apolipoproteínas E/genética , Veteranos , Brometo de Piridostigmina/toxicidade , Praguicidas/toxicidade , Substâncias Perigosas/toxicidade , Masculino , Feminino , Pessoa de Meia-Idade , Fumaça/efeitos adversos
3.
Nature ; 531(7593): 202-5, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26934226

RESUMO

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

4.
Diabet Med ; 37(12): 2116-2123, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32510602

RESUMO

AIMS: To estimate the rate at which people with diabetes and a low risk of foot ulceration change diabetic foot ulceration risk status over time, and to estimate the rate of ulceration, amputation and death among this population. METHODS: We conducted an observational study of 10 421 people with diabetes attending foot screening in an outpatient setting in NHS Fife, UK, using routinely collected data from a national diabetes register, NHS SCI Diabetes. We estimated the proportion of people who changed risk status and the cumulative incidence of ulceration, amputation and death, respectively, among people with diabetes at low risk of diabetic foot ulceration at 2-year follow-up. RESULTS: At 2-year follow-up, 5.1% (95% CI 4.7, 5.6) of people with diabetes classified as low risk at their first visit had progressed to moderate risk. The cumulative incidence of ulceration, amputation and death was 0.4% (95% CI 0.3, 0.6), 0.1% (95% CI 0.1, 0.2) and 3.4% (95% CI 3.1, 3.8), respectively. CONCLUSIONS: At 2-year follow-up, 5% of people at low risk of diabetic foot ulceration changed clinical risk status and <1% of people experienced foot ulceration or amputation. These findings provide information which will help to inform the current debate regarding optimal foot screening intervals.


Assuntos
Amputação Cirúrgica/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Pé Diabético/epidemiologia , Mortalidade , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Medição de Risco , Reino Unido/epidemiologia
5.
Diabet Med ; 35(11): 1480-1493, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30102422

RESUMO

AIMS: Diabetes guidelines recommend screening for the risk of foot ulceration but vary substantially in the underlying evidence base. Our purpose was to derive and validate a prognostic model of independent risk factors for foot ulceration in diabetes using all available individual patient data from cohort studies conducted worldwide. METHODS: We conducted a systematic review and meta-analysis of individual patient data from 10 cohort studies of risk factors in the prediction of foot ulceration in diabetes. Predictors were selected for plausibility, availability and low heterogeneity. Logistic regression produced adjusted odds ratios (ORs) for foot ulceration by ulceration history, monofilament insensitivity, any absent pedal pulse, age, sex and diabetes duration. RESULTS: The 10 studies contained data from 16 385 participants. A history of foot ulceration produced the largest OR [6.59 (95% CI 2.49 to 17.45)], insensitivity to a 10 g monofilament [3.18 (95% CI 2.65 to 3.82)] and any absent pedal pulse [1.97 (95% CI 1.62 to 2.39)] were consistently, independently predictive. Combining three predictors produced sensitivities between 90.0% (95% CI 69.9% to 97.2%) and 95.3% (95% CI 84.5% to 98.7%); the corresponding specificities were between 12.1% (95% CI 8.2% to 17.3%) and 63.9% (95% CI 61.1% to 66.6%). CONCLUSIONS: This prognostic model of only three risk factors, a history of foot ulceration, an inability to feel a 10 g monofilament and the absence of any pedal pulse, compares favourably with more complex approaches to foot risk assessment recommended in clinical diabetes guidelines.


Assuntos
Pé Diabético/diagnóstico , Modelos Estatísticos , Técnicas de Apoio para a Decisão , Pé Diabético/epidemiologia , Humanos , Análise Multivariada , Prognóstico
6.
Nat Genet ; 1(5): 345-7, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1302033

RESUMO

Mutations at codon 717 in exon 17 of the beta-amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families. We have identified a double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which co-segregates with the disease in two large (probably related) early-onset Alzheimer's disease families from Sweden. Two base pair transversions (G to T, A to C) from the normal sequence predict Lys to Asn and Met to Leu amino acid substitutions at codons 670 and 671 of the APP transcript. This mutation occurs at the amino terminal of beta-amyloid and may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. Thus, pathogenic mutations in APP frame the beta-amyloid sequence.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Mutação Puntual , Doença de Alzheimer/patologia , Sequência de Aminoácidos , Sequência de Bases , Encéfalo/patologia , Códon/genética , Éxons , Feminino , Ligação Genética , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Linhagem , Transcrição Gênica
7.
Harmful Algae ; 117: 102286, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35944953

RESUMO

In southwest Florida, Karenia brevis (K. brevis) blooms occur frequently, can be very intense and persist over several years. Individuals living in coastal communities around the Gulf of Mexico are particularly vulnerable to brevetoxins released by K. brevis in seawater and carried inland within marine aerosol. Exposure to K. brevis occurs during residential, recreational, and occupational activities and has been associated with upper respiratory tract (URT) symptoms in healthy and medically vulnerable individuals. Additionally, ingestion of brevetoxin-contaminated seafood causes neurotoxic shellfish poisoning (NSP), and severe headaches prompting emergency department visits which occur in excess during K. brevis blooms. The current study examined a dose-response relationship between K. brevis in coastal waters and URT and NSP-like symptoms and headaches among southwest Florida residents. Data on past medical history (PMH) and medical symptoms were collected from the participants (n = 258) in five southwest Florida counties between June 2019 to August 2021. A dose-response relationship was observed between K. brevis blooms and reporting of URT and NSP-like symptoms and headaches. Reporting of NSP-like symptoms was higher among participants with a PMH of migraines, chronic fatigue syndrome (CFS) and mild memory loss, while the association of headaches with K. brevis blooms was accentuated among individuals with a PMH of migraines. These results suggest further investigations into the threshold of aerosolized brevetoxin dose required to elicit URT, headaches and/or NSP-like symptoms. These symptoms ultimately cause significant public health safety concerns, primarily among vulnerable populations with preexisting neurological conditions.


Assuntos
Dinoflagellida , Transtornos de Enxaqueca , Intoxicação por Frutos do Mar , Cefaleia , Humanos , Neurotoxinas , Sistema Respiratório
8.
Int J Geriatr Psychiatry ; 26(10): 1038-45, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21905098

RESUMO

BACKGROUND: Nilvadipine may lower rates of conversion from mild-cognitive impairment to Alzheimer's disease (AD), in hypertensive patients. However, it remains to be determined whether treatment with nilvadipine is safe in AD patients, given the higher incidence of orthostatic hypotension (OH) in this population, who may be more likely to suffer from symptoms associated with the further exaggeration of a drop in BP. OBJECTIVE: The aim of this study was to investigate the safety and tolerability of nilvadipine in AD patients. METHODS: AD patients in the intervention group (n = 56) received nilvadipine 8 mg daily over 6-weeks, compared to the control group (n = 30) who received no intervention. Differences in systolic (SBP) and diastolic (DBP) blood pressure, before and after intervention, was assessed using automated sphygmomanometer readings and ambulatory BP monitors (ABP), and change in OH using a finometer. Reporting of adverse events was monitored throughout the study. RESULTS: There was a significant reduction in the SBP of treated patients compared to non-treated patients but no significant change in DBP. Individuals with higher initial blood pressure (BP) had greater reduction in BP but individuals with normal BP did not experience much change in their BP. While OH was present in 84% of the patients, there was no further drop in BP recorded on active stand studies. There were no significant differences in adverse event reporting between groups. CONCLUSION: Nilvadipine was well tolerated by patients with AD. This study supports further investigation of its efficacy as a potential treatment for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Nifedipino/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/efeitos adversos
9.
J Exp Med ; 192(12): 1719-30, 2000 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-11120769

RESUMO

We recently described a novel way to isolate populations of antigen-reactive CD4(+) T cells with a wide range of reactivity to a specific antigen, using immunization with a fixed dose of nominal antigen and FACS((R)) sorting by CD4(high) expression. Phenotypic, FACS((R)), functional, antibody inhibition, and major histocompatibility complex-peptide tetramer analyses, as well as T cell receptor Vbeta sequence analyses, of the antigen-specific CD4(high) T cell populations demonstrated that a diverse sperm whale myoglobin 110-121-reactive CD4(+) T cell repertoire was activated at the beginning (day 3 after immunization) of the immune response. Within 6 d of immunization, lower affinity clones were lost from the responding population, leaving an expanded population of oligoclonal, intermediate affinity (and residual high affinity) T cells. This T cell subset persisted for at least 4 wk after immunization and dominated the secondary immune response. These data provide evidence that CD4(+) T cell repertoire selection occurs early in the immune response in vivo and suggest that persistence and expansion of a population of oligoclonal, intermediate affinity T cells is involved in CD4(+) T cell memory.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Regiões Determinantes de Complementaridade/genética , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Antígenos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células Clonais/imunologia , Regiões Determinantes de Complementaridade/imunologia , Citometria de Fluxo , Imunização , Memória Imunológica/imunologia , Cinética , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Mioglobina/imunologia , Fragmentos de Peptídeos/imunologia , Análise de Sequência
10.
Public Health ; 124(3): 125-30, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20207381

RESUMO

OBJECTIVES: To establish the theoretical and perceived links between area regeneration and health in a Scottish context in order to inform a comprehensive evaluation of regeneration activity. The evaluation will include health outcomes. STUDY DESIGN: Mixed method combining and comparing key informant interviews with policy analysis. METHODS: Analysis of identified links between elements of regeneration activity and health was undertaken of published policies and strategies which described regeneration for Scotland and the city of Glasgow. Interviews with key informants explored their understanding of the inputs to regeneration, and the pathways between regeneration and better health outcomes. RESULTS: The policy analysis and interviews revealed a holistic approach to a complex problem. Both identified a need for action to improve housing, neighbourhoods and services, education, employment, community participation and social issues. Improved health was identified as an emergent property. Interviewees identified a need to augment the established structural components with a more person-centred approach, fostering confidence and higher aspirations, but were uncertain how to achieve this. The interviews revealed a lack of confidence that current practice would deliver all the components of the holistic model. CONCLUSIONS: A holistic model of regeneration appears to inform policy, but is proving difficult to deliver. Improved health and reduced health inequalities were not primary objectives but emergent properties. In light of this, the ability of regeneration to actively maximize positive health impacts, particularly if this requires focused planning or opportunity costs to other activities, is questioned.


Assuntos
Política de Saúde , Promoção da Saúde/tendências , Disparidades nos Níveis de Saúde , Saúde Pública , Marketing Social , Promoção da Saúde/organização & administração , Humanos , Entrevistas como Assunto , Programas Nacionais de Saúde , Política , Avaliação de Programas e Projetos de Saúde , Habitação Popular , Escócia , Meios de Transporte
11.
Prim Dent Care ; 17(4): 161-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20887669

RESUMO

Sectional imaging is a useful tool for the dental practitioner, especially in the fields of oral surgery and implant dentistry. Until recently, the most readily available way to gain three-dimensional information has been computed tomography (CT). The main drawbacks to using this technique have been the substantial dose of ionising radiation and accessibility. Cone-beam computed tomography (CBCT) allows 3D imaging to be made using bespoke equipment designed for the dental practice environment. Exposure to ionising radiation is substantially lower than that for an average x-ray CT scan, but in most cases is still greater than when other dental radiographs are taken. Various guidelines are now in the public domain and these are referenced within this review of CBCT. The concepts of appropriate selection criteria and optimisation of imaging parameters are stressed, along with compliance with the regulations relating to the use of ionising radiation-Ionising Radiation Regulations 1999 and Ionising Radiation (Medical Exposure) Regulations 2000-and training requirements.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Consultórios Odontológicos , Radiografia Dentária/métodos , Fidelidade a Diretrizes , Humanos , Imageamento Tridimensional/métodos , Guias de Prática Clínica como Assunto , Doses de Radiação , Intensificação de Imagem Radiográfica
12.
Science ; 200(4341): 489-94, 1978 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-17839416

RESUMO

Atmospherically induced phase perturbations have for years limited the resolution of large optical astronomical telescopes. A prototype telescope system with six movable elements has successfully corrected these phase perturbations. This use of real-time image sharpening has restored stellar images to the diffraction limit (in one dimension) for a 30-centimeter telescope. The double-star image presented indicates that the bulk of the atmospherically induced wave-front phase change occurred within 2 kilometers of the telescope. This implies that, at least for conditions similar to those of our measurement, real-time correction can be accomplished simultaneously for a region at least several arc seconds in angular size. With the present apparatus the technique should be practical for objects as dim as fifth magnitude, and with improvements the technique holds the promise of active image restoration for objects as dim as ninth magnitude.

13.
Science ; 291(5508): 1537-40, 2001 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-11222857

RESUMO

Previous findings suggest that during cognate T cell-B cell interactions, major histocompatability complex (MHC) class II molecules transduce signals, leading to Src-family kinase activation, Ca2+ mobilization, and proliferation. Here, we show that antigen stimulation of resting B cells induces MHC class II molecules to associate with Immunoglobulin (Ig)-alpha/Ig-beta (CD79a/CD79b) heterodimers, which function as signal transducers upon MHC class II aggregation by the T cell receptor (TCR). The B cell receptor (BCR) and MHC class II/Ig-alpha/Ig-beta are distinct complexes, yet class II-associated Ig-alpha/beta appears to be derived from BCR. Hence, Ig-alpha/beta are used in a sequential fashion for transduction of antigen and cognate T cell help signals.


Assuntos
Antígenos CD/metabolismo , Linfócitos B/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Animais , Antígenos/imunologia , Linfócitos B/metabolismo , Antígenos CD79 , Células Cultivadas , Dimerização , Ativação Enzimática , Antígenos de Histocompatibilidade Classe II/imunologia , Immunoblotting , Ativação Linfocitária , Camundongos , Camundongos Transgênicos , Fosforilação , Fosfotirosina/metabolismo , Testes de Precipitina , Proteínas Tirosina Quinases/metabolismo , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transcrição Gênica
14.
Science ; 286(5448): 2352-5, 1999 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-10600748

RESUMO

Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Antígenos CD40/metabolismo , Glicoproteínas de Membrana/metabolismo , Microglia/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Antígenos CD40/biossíntese , Ligante de CD40 , Morte Celular , Células Cultivadas , Interferon gama/farmacologia , Interleucinas/farmacologia , Ligantes , Glicoproteínas de Membrana/farmacologia , Camundongos , Camundongos Transgênicos , Microglia/citologia , Microglia/imunologia , Neurônios/citologia , Fragmentos de Peptídeos/farmacologia , Fosforilação , Transdução de Sinais , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/farmacologia , Proteínas tau/metabolismo
15.
Cell Death Differ ; 14(3): 447-52, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16946732

RESUMO

The Bcl-2 family member Bax plays a critical role in apoptosis. In healthy resting cells, Bax resides in the cytoplasm and loosely attached to the mitochondrial membrane. Apoptotic stimuli induce Bax activation, which is characterized by translocation and multimerization on the mitochondrial membrane surface resulting in exposure of an amino terminal epitope recognized by the monoclonal antibody 6A7. To understand the structural changes that occur during Bax activation, we determined the crystal structure of a Bax peptide bound to the 6A7 Fab fragment to a resolution of 2.3 A. The structure reveals the conformation of the 6A7 peptide epitope on Bax in the activated form and elucidates the extensive structural changes that Bax must undergo during the conversion from its native to its activated conformation.


Assuntos
Fragmentos Fab das Imunoglobulinas/química , Peptídeos/química , Conformação Proteica , Proteína X Associada a bcl-2/química , Anticorpos , Sítios de Ligação , Linhagem Celular Tumoral , Cristalização , Epitopos/química , Epitopos/metabolismo , Humanos , Fragmentos Fab das Imunoglobulinas/metabolismo , Modelos Moleculares , Peptídeos/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Proteína X Associada a bcl-2/metabolismo
16.
Br J Dermatol ; 159(4): 773-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18834482

RESUMO

BACKGROUND: Placebo-controlled trials are useful in identifying effective treatments where none has existed, but their continued use once efficacy is established arguably contravenes ethical standards for medical research. OBJECTIVES: To consider whether sufficient evidence exists to recommend the abandonment of vehicle-controlled studies in trials of topical treatments for athlete's foot. METHODS: We searched nine electronic databases and bibliographies of review articles as part of an ongoing Cochrane systematic review from 1966 to 2007. Randomized controlled trials (RCTs) using a vehicle control design involving participants with a mycological diagnosis of a dermatophyte infection of the skin of the foot were included. RESULTS: Allylamines, azoles, ciclopiroxolamine, tolnaftate, butenafine and undecanoates were all more effective than vehicle controls. Evidence of the superiority of azole creams over vehicle controls was fairly consistent from 1975 onwards. Data from patients treated with allylamines have shown their superior effects relative to vehicle controls since 1991 for even short-term outcomes. CONCLUSIONS: The superiority of allylamines and azoles over vehicle in vehicle-controlled trials has been well established, and data demonstrating this fact have been available since the completion of early RCTs. These preparations are effective and safe, and investigators of RCTs evaluating topical treatments for athlete's foot need to choose potential comparators as control interventions in the light of this knowledge and to consider the ethics of withholding effective treatment from patients who seek treatment for this common foot infection.


Assuntos
Antifúngicos/administração & dosagem , Emolientes/administração & dosagem , Tinha dos Pés/tratamento farmacológico , Administração Tópica , Humanos , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
QJM ; 100(2): 65-86, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17277315

RESUMO

Clinical guidelines recommend that all patients with diabetes should be screened annually to establish their risk of foot ulceration. The aim of this systematic review was to quantify the predictive value of diagnostic tests, physical signs and elements from the patient's history in relation to diabetic foot ulcers. Observational studies were identified from: electronic databases (MEDLINE, EMBASE and CINAHL); bibliographies of studies meeting the inclusion criteria; review articles and clinical guidelines; direct contact with authors. Published reports of cohort and case-control studies were considered for inclusion. Pooled estimates were calculated from absolute numbers as weighted mean differences, standard mean differences or odds ratios. Adjusted odds ratios from published reports were also extracted. We identified five case-control and 11 cohort studies. The incidence of foot ulcers ranged from 8% to 17% in the cohort studies, with varying lengths of follow-up. Diagnostic tests and physical signs that detect peripheral neuropathy (biothesiometry, monofilaments and absent ankle reflexes), and those that detect excessive plantar pressure (peak plantar pressure and joint deformity) were all significantly associated with future diabetic foot ulceration. However, there was a paucity of evidence concerning the predictive value of symptoms and signs. Further research is needed to establish the independent factors associated with diabetic foot ulceration, particularly elements from a patient's history and physical examination.


Assuntos
Neuropatias Diabéticas/diagnóstico , Úlcera do Pé/etiologia , Neuropatias Diabéticas/complicações , Humanos , Sensibilidade e Especificidade
18.
Cochrane Database Syst Rev ; (3): CD001434, 2007 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-17636672

RESUMO

BACKGROUND: Fungal infections of the feet normally occur in the outermost layer of the skin (epidermis). The skin between the toes is a frequent site of infection which can cause pain and itchiness. Fungal infections of the nail (onychomycosis) can affect the entire nail plate. OBJECTIVES: To assess the effects of topical treatments in successfully treating (rate of treatment failure) fungal infections of the skin of the feet and toenails and in preventing recurrence. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE and EMBASE (from inception to January 2005). We screened the Science Citation Index, BIOSIS, CAB - Health and Healthstar, CINAHL DARE, NHS Economic Evaluation Database and EconLit (March 2005). Bibliographies were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) using participants who had mycologically diagnosed fungal infections of the skin and nails of the foot. DATA COLLECTION AND ANALYSIS: Two authors independently summarised the included trials and appraised their quality of reporting using a structured data extraction tool. MAIN RESULTS: Of the 144 identified papers, 67 trials met the inclusion criteria. Placebo-controlled trials yielded the following pooled risk ratios (RR) of treatment failure for skin infections: allylamines RR 0.33 (95% CI 0.24 to 0.44); azoles RR 0.30 (95% CI 0.20 to 0.45); ciclopiroxolamine RR 0.27 (95% CI 0.11 to 0.66); tolnaftate RR 0.19 (95% CI 0.08 to 0.44); butenafine RR 0.33 (95% CI 0.24 to 0.45); undecanoates RR 0.29 (95% CI 0.12 - 0.70). Meta-analysis of 11 trials comparing allylamines and azoles showed a risk ratio of treatment failure RR 0.63 (95% CI 0.42 to 0.94) in favour of allylamines. Evidence for the management of topical treatments for infections of the toenails is sparser. There is some evidence that ciclopiroxolamine and butenafine are both effective but they both need to be applied daily for prolonged periods (at least 1 year). The 6 trials of nail infections provided evidence that topical ciclopiroxolamine has poor cure rates and that amorolfine might be substantially more effective but more research is required. AUTHORS' CONCLUSIONS: Placebo-controlled trials of allylamines and azoles for athlete's foot consistently produce much higher percentages of cure than placebo. Allylamines cure slightly more infections than azoles and are now available OTC. Further research into the effectiveness of antifungal agents for nail infections is required.


Assuntos
Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Dermatoses do Pé/tratamento farmacológico , Onicomicose/tratamento farmacológico , Administração Tópica , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Community Dent Health ; 24(4): 233-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18246841

RESUMO

OBJECTIVES: Evaluation of advance telephone prompting on the response rate to a postal, self-completed questionnaire. To provide an estimate of the cost of such a strategy. METHOD: A sample of 315 GDPs was randomly selected from a randomised database of GDPs practicing in Scotland. 157 GDPs were randomly allocated to receive an advance telephone prompt, via the practice receptionist; 158 were allocated to a control group. Four days after prompting all trial participants were mailed identical questionnaires, cover letter and postage paid return envelope. RESULTS: Response rates: 53%--advance telephone prompt group and 40%--control group. The effect size, 13%, was found to be statistically significant, p = 0.026. Total estimated strategy costs: 74.00 pounds sterling. The incremental cost was estimated to be 4.93 pounds sterling for each additional response. CONCLUSIONS: Advance telephone prompting of GDP's, via the practice receptionist, statistically significantly improves the response rate to a postal self-completed questionnaire. This is estimated to be a cost effective strategy for improving response rates to postal questionnaires.


Assuntos
Odontologia Geral/estatística & dados numéricos , Sistemas de Alerta/estatística & dados numéricos , Telefone , Feminino , Humanos , Masculino , Sistemas de Alerta/economia , Escócia , Inquéritos e Questionários
20.
Pain Pract ; 7(3): 279-84, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17714108

RESUMO

INTRODUCTION: Implantable pain therapy devices for chronic pain include spinal cord stimulators (SCS) and intrathecal drug delivery systems (IDDS). A number of different complications can occur after implantation of these devices, but among the most serious is infection. Based on Centers for Disease Control and Prevention guidelines for prevention of surgical site infection, published literature on infection risk with implantable pain therapy devices, and recommendations from groups within our own our institution, we introduced infection control measures for all patients receiving either SCS or IDDS. METHODS: After approval from the Institutional Review Board, we performed a retrospective review of patients undergoing primary implantation of SCS or IDDS before and after introduction at our institution of safety measures designed to reduce device-related infection. We compared infection incidence and compliance to infection precautions before and after introduction of these measures. RESULTS: Thirty-four SCS or IDDS were implanted before implementation of the infection control measures and 58 were placed after. Five device-related infections occurred. Adherence to most infection precautions improved during the study period, but 100% compliance was seen only with venue used for implantation. Infection incidence declined after introduction of the safety measures, but the reduction was not statistically significant. CONCLUSIONS: Introduction of infection control measures for implantable pain therapy devices improved adherence to most infection precautions in our practice. Lack of specific documentation could have hindered practice surveillance within our group. A tool to document performance of infection control measures would be useful not only as a marker of compliance but could also serve as a reminder to perform certain safety measures.


Assuntos
Analgesia/métodos , Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Bombas de Infusão Implantáveis , Adulto , Analgesia/efeitos adversos , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/tendências , Infecção Hospitalar/microbiologia , Contaminação de Equipamentos/prevenção & controle , Feminino , Humanos , Controle de Infecções/tendências , Bombas de Infusão Implantáveis/efeitos adversos , Bombas de Infusão Implantáveis/microbiologia , Masculino , Pessoa de Meia-Idade , Dor/microbiologia , Manejo da Dor
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