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1.
Circ Cardiovasc Imaging ; 12(8): e008574, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31382765

RESUMO

BACKGROUND: Coronary 18F-fluoride positron emission tomography identifies ruptured and high-risk atherosclerotic plaque. The optimal method to identify, to quantify, and to categorize increased coronary 18F-fluoride uptake and determine its reproducibility has yet to be established. This study aimed to optimize the identification, quantification, categorization, and scan-rescan reproducibility of increased 18F-fluoride activity in coronary atherosclerotic plaque. METHODS: In a prospective observational study, patients with multi-vessel coronary artery disease underwent serial 18F-fluoride positron emission tomography. Coronary 18F-fluoride activity was visually assessed, quantified, and categorized with reference to maximal tissue to background ratios. Levels of agreement for both visual and quantitative methods were determined between scans and observers. RESULTS: Thirty patients (90% male, 20 patients with stable coronary artery disease, and 10 with recent type 1 myocardial infarction) underwent paired serial positron emission tomography-coronary computed tomography angiography imaging within an interval of 12±5 days. A mean of 3.7±1.8 18F-fluoride positive plaques per patient was identified after recent acute coronary syndrome, compared with 2.4±2.3 positive plaques per patient in stable coronary artery disease. The bias in agreement in maximum tissue to background ratio measurements in visually positive plaques was low between observers (mean difference, -0.01; 95% limits of agreement, -0.32 to 0.30) or between scans (mean difference, 0.06; 95% limits of agreement, -0.49 to 0.61). Good agreement in the categorization of focal 18F-fluoride uptake was achieved using visual assessment alone (κ=0.66) and further improved at higher maximum tissue to background ratio values. CONCLUSIONS: Coronary 18F-fluoride activity is a precise and reproducible metric in the coronary vasculature. The analytical performance of 18F-fluoride is sufficient to assess the prognostic utility of this radiotracer as a noninvasive imaging biomarker of plaque vulnerability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110303 and NCT02278211.

3.
BMJ Open ; 8(8): e021944, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30166303

RESUMO

INTRODUCTION: The major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist). METHODS AND ANALYSIS: Patients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland. ETHICS AND DISSEMINATION: MS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: NCT01910259; 2012-005394-31; ISRCTN28440672.

4.
Lancet ; 392(10151): 919-928, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30170853

RESUMO

BACKGROUND: High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome. METHODS: In this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6-12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123. FINDINGS: Between June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620). INTERPRETATION: Use of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. FUNDING: The British Heart Foundation.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Síndrome Coronariana Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Valor Preditivo dos Testes
5.
Pharm Stat ; 17(6): 854-865, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30215881

RESUMO

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. Before deciding on a particular design, it is generally advisable to carry out a simulation study to characterise the properties of candidate designs under a range of plausible assumptions. The implementation of such pre-trial simulation studies presents many challenges and requires considerable statistical programming effort and time. Despite the scale and complexity, there is little existing literature to guide the implementation of such projects using commonly available software. This Teacher's Corner article provides a practical step-by-step guide to implementing such simulation studies including how to specify and fit a Bayesian model in WinBUGS or OpenBUGS using SAS, and how results from the Bayesian analysis may be pulled back into SAS and used for adaptation of allocation probabilities before simulating subsequent stages of the trial. The interface between the two software platforms is described in detail along with useful tips and tricks. A key strength of our approach is that the entire exercise can be defined and controlled from within a single SAS program.

6.
BMJ Open ; 8(1): e019431, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29391369

RESUMO

OBJECTIVE: Simple forms of blood pressure (BP) telemonitoring require patients to text readings to central servers creating an opportunity for both entry error and manipulation. We wished to determine if there was an apparent preference for particular end digits and entries which were just below target BPs which might suggest evidence of data manipulation. DESIGN: Prospective cohort study SETTING: 37 socioeconomically diverse primary care practices from South East Scotland. PARTICIPANTS: Patients were recruited with hypertension to a telemonitoring service in which patients submitted home BP readings by manually transcribing the measurements into text messages for transmission ('patient-texted system'). These readings were compared with those from primary care patients with uncontrolled hypertension using a system in which readings were automatically transmitted, eliminating the possibility of manipulation of values ('automatic-transmission system'). METHODS: A generalised estimating equations method was used to compare BP readings between the patient-texted and automatic-transmission systems, while taking into account clustering of readings within patients. RESULTS: A total of 44 150 BP readings were analysed on 1068 patients using the patient-texted system compared with 20 705 readings on 199 patients using the automatic-transmission system. Compared with the automatic-transmission data, the patient-texted data showed a significantly higher proportion of occurrences of both systolic and diastolic BP having a zero end digit (OR 2.1, 95% CI 1.7 to 2.6) although incidence was <2% of readings. Similarly, there was a preference for systolic 134 and diastolic 84 (the threshold for alerts was 135/85) (134 systolic BP OR 1.5, 95% CI 1.3 to 1.8; 84 diastolic BP OR 1.5, 95% CI 1.3 to 1.9). CONCLUSION: End-digit preference for zero numbers and specific-value preference for readings just below the alert threshold exist among patients in self-reporting their BP using telemonitoring. However, the proportion of readings affected is small and unlikely to be clinically important. TRIAL REGISTRATION NUMBER: ISRCTN72614272; Post-results.


Assuntos
Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea , Hipertensão/fisiopatologia , Conceitos Matemáticos , Autocuidado , Telemedicina , Mensagem de Texto , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escócia , Autorrelato
7.
Acta Radiol ; 59(4): 418-424, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28707958

RESUMO

Background Dedicated blood-pool contrast agents combined with optimal angiographic protocols could improve the diagnostic accuracy of thoracic magnetic resonance angiography (MRA). Purpose To assess the clinical utility of Gadofesveset-enhanced imaging and compare an optimized steady-state (SS) sequence against conventional first-pass dynamic multi-phase (DMP) imaging. Material and Methods Twenty-nine patients (17 men, 12 women; mean age = 42.7, age range = 18-72 years) referred for MR thoracic venography were recruited. Imaging was performed on a 1.5T MRI system. A blood-pool contrast agent (Gadofesveset) was administered intravenously. Thirty temporal phases were acquired using DMP. This was immediately followed by a high-resolution SS sequence. Three radiologists in consensus reviewed seven thoracic vascular segments after randomizing the acquisition order. Image quality, stenoses, thromboses, and artifacts were graded using a categorical scoring system. The image quality for both approaches was compared using Wilcoxon's signed-rank test. McNemar's test was used to compare the proportions of stenosis grades, thrombus and artifacts. Results SS had significantly better image quality than DMP (3.14 ± 0.73 and 2.92 ± 0.60, respectively; P < 0.001). SS identified fewer stenoses (>50%) than DMP; the differences in stenosis categorizations was statistically significant ( P = 0.013). There was no significant difference in the proportions of vessels with thromboses ( P = 0.617). DMP produced more artifacts than SS (101 versus 85); however, the difference was not statistically significant ( P = 0.073). Conclusion Gadofesveset-enhanced thoracic angiography is clinically feasible. SS imaging produces better image quality and fewer artifacts than conventional DMP imaging.


Assuntos
Meios de Contraste , Gadolínio , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Compostos Organometálicos , Adolescente , Adulto , Idoso , Artefatos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tórax/irrigação sanguínea , Tórax/diagnóstico por imagem , Adulto Jovem
8.
Trials ; 18(1): 623, 2017 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-29282142

RESUMO

BACKGROUND: Few interventions are proven to increase recruitment in clinical trials. Recruitment to RESTART, a randomised controlled trial of secondary prevention after stroke due to intracerebral haemorrhage, has been slower than expected. Therefore, we sought to investigate an intervention to boost recruitment to RESTART. METHODS/DESIGN: We conducted a stepped-wedge, cluster randomised trial of a complex intervention to increase recruitment, embedded within the RESTART trial. The primary objective was to investigate if the PRIME complex intervention (a recruitment co-ordinator who conducts a recruitment review, provides access to bespoke stroke audit data exports, and conducts a follow-up review after 6 months) increases the recruitment rate to RESTART. We included 72 hospital sites located in England, Wales, or Scotland that were active in RESTART in June 2015. All sites began in the control state and were allocated using block randomisation stratified by hospital location (Scotland versus England/Wales) to start the complex intervention in one of 12 different months. The primary outcome was the number of patients randomised into RESTART per month per site. We quantified the effect of the complex intervention on the primary outcome using a negative binomial, mixed model adjusting for site, December/January months, site location, and background time trends in recruitment rate. RESULTS: We recruited and randomised 72 sites and recorded their monthly recruitment to RESTART over 24 months (March 2015 to February 2017 inclusive), providing 1728 site-months of observations for the primary analysis. The adjusted rate ratio for the number of patients randomised per month after allocation to the PRIME complex intervention versus control time before allocation to the PRIME complex intervention was 1.06 (95% confidence interval 0.55 to 2.03, p = 0.87). Although two thirds of respondents to the 6-month follow-up questionnaire agreed that the audit reports were useful, only six patients were reported to have been randomised using the audit reports. Respondents frequently reported resource and time pressures as being key barriers to running the audit reports. CONCLUSION: The PRIME complex intervention did not significantly improve the recruitment rate to RESTART. Further research is needed to establish if PRIME might be beneficial at an earlier stage in a prevention trial or for prevention dilemmas that arise more often in clinical practice.

9.
J Neurol Neurosurg Psychiatry ; 88(12): 1045-1051, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28912299

RESUMO

BACKGROUND: To validate a short cognitive test: the Test Your Memory for Mild Cognitive Impairment (TYM-MCI) in the diagnosis of patients with amnestic mild cognitive impairment or mild Alzheimer's disease (aMCI/AD). METHODS: Two hundred and two patients with mild memory problems were recruited. All had 'passed' the Mini-Mental State Examination (MMSE). Patients completed the TYM-MCI, the Test Your Memory test (TYM), MMSE and revised Addenbrooke's Cognitive Examination (ACE-R), had a neurological examination, clinical diagnostics and multidisciplinary team review. RESULTS: As a single test, the TYM-MCI performed as well as the ACE-R in the distinction of patients with aMCI/AD from patients with subjective memory impairment with a sensitivity of 0.79 and specificity of 0.91. Used in combination with the ACE-R, it provided additional value and identified almost all cases of aMCI/AD. The TYM-MCI correctly classified most patients who had equivocal ACE-R scores. Integrated discriminant improvement analysis showed that the TYM-MCI added value to the conventional memory assessment. Patients initially diagnosed as unknown or with subjective memory impairment who were later rediagnosed with aMCI/AD scored poorly on their original TYM-MCI. CONCLUSION: The TYM-MCI is a powerful short cognitive test that examines verbal and visual recall and is a valuable addition to the assessment of patients with aMCI/AD. It is simple and cheap to administer and requires minimal staff time and training.


Assuntos
Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Doença de Alzheimer/psicologia , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Rememoração Mental , Pessoa de Meia-Idade , Exame Neurológico , Reprodutibilidade dos Testes
10.
Int J Chron Obstruct Pulmon Dis ; 12: 1221-1231, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28458534

RESUMO

Telehealth programs to promote early identification and timely self-management of acute exacerbations of chronic obstructive pulmonary diseases (AECOPDs) have yielded disappointing results, in part, because parameters monitored (symptoms, pulse oximetry, and spirometry) are weak predictors of exacerbations. PURPOSE: Breathing rate (BR) rises during AECOPD and may be a promising predictor. Devices suitable for home use to measure BR have recently become available, but their accuracy, acceptability, and ability to detect changes in people with COPD is not known. PATIENTS AND METHODS: We compared five BR monitors, which used different monitoring technologies, with a gold standard (Oxycon Mobile®; CareFusion®, a subsidiary of Becton Dickinson, San Diego, CA, USA). The monitors were validated in 21 stable COPD patients during a 57-min "activities of daily living protocol" in a laboratory setting. The two best performing monitors were then tested in a 14-day trial in a home setting in 23 stable COPD patients to determine patient acceptability and reliability of signal. Acceptability was explored in qualitative interviews. The better performing monitor was then given to 18 patients recruited during an AECOPD who wore the monitor to observe BR during the recovery phase of an AECOPD. RESULTS: While two monitors demonstrated acceptable accuracy compared with the gold standard, some participants found them intrusive particularly when ill with an exacerbation, limiting their potential utility in acute situations. A reduction in resting BR during the recovery from an AECOPD was observed in some, but not in all participants and there was considerable day-to-day individual variation. CONCLUSION: Resting BR shows some promise in identifying exacerbations; however, further prospective study to assess this is required.


Assuntos
Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Testes de Função Respiratória/instrumentação , Mecânica Respiratória , Telemedicina/instrumentação , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Desenho de Equipamento , Exercício , Estudos de Viabilidade , Feminino , Frequência Cardíaca , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Pesquisa Qualitativa , Reprodutibilidade dos Testes , Testes de Função Respiratória/normas , Telemedicina/normas
12.
Trials ; 18(1): 94, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28253897

RESUMO

BACKGROUND: Promoting Recruitment using Information Management Efficiently (PRIME) is a stepped wedge, cluster randomised trial-within-a-trial of a complex intervention to help sites in the United Kingdom to attain their own target number of participants to recruit to the REstart or STop Antithrombotics Randomised Trial (RESTART, ISRCTN71907627). METHODS: Seventy-two hospital sites had opted into PRIME and were randomly allocated (using a computer-generated block randomisation algorithm, stratified by hospital location) to one of 12 months in which a complex intervention would be delivered. All sites began in the control state. The primary outcome is the total number of patients randomised into RESTART per month per site, which will be analysed in a negative binomial generalised linear mixed model. Secondary outcomes include the proportion of sites using stroke databases to identify potentially eligible patients before PRIME, frequency of using bespoke stroke audit data exports during PRIME, barriers to recruitment in PRIME, barriers to using the bespoke stroke audit data exports, and disadvantages of the bespoke stroke audit exports identified by PRIME sites. PRIME began in September 2015. The last intervention will be delivered in August 2016. Six-month follow-up will be complete in February 2017. This statistical analysis plan was written and submitted for publication before all sites received the PRIME intervention and before outcome data were known. DISCUSSION: Final results of PRIME will be analysed and disseminated in 2017. TRIAL REGISTRATION: Northern Ireland Hub for Trials Methodology Research SWAT repository (SWAT22).


Assuntos
Hemorragia Cerebral/prevenção & controle , Registros Eletrônicos de Saúde , Fibrinolíticos/administração & dosagem , Gestão da Informação , Seleção de Pacientes , Inibidores da Agregação de Plaquetas/administração & dosagem , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Protocolos Clínicos , Interpretação Estatística de Dados , Esquema de Medicação , Registros Eletrônicos de Saúde/estatística & dados numéricos , Fibrinolíticos/efeitos adversos , Humanos , Gestão da Informação/estatística & dados numéricos , Modelos Estatísticos , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Fatores de Risco , Tamanho da Amostra , Prevenção Secundária/estatística & dados numéricos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Reino Unido
13.
Trials ; 18(1): 22, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28245843

RESUMO

BACKGROUND: Research into methods to boost recruitment has been identified as the highest priority for randomised controlled trial (RCT) methodological research in the United Kingdom. Slow recruitment delays the delivery of research and inflates costs. Using electronic patient records has been shown to boost recruitment to ongoing RCTs in primary care by identifying potentially eligible participants, but this approach remains relatively unexplored in secondary care, and for stroke in particular. METHODS/DESIGN: The REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) is an ongoing RCT of secondary prevention after stroke due to intracerebral haemorrhage. Promoting Recruitment using Information Management Efficiently (PRIME) is a stepped-wedge cluster randomised trial of a complex intervention to help RESTART sites increase their recruitment and attain their own target numbers of participants. Seventy-two hospital sites that were located in England, Wales or Scotland and were active in RESTART in June 2015 opted into PRIME. Sites were randomly allocated (using a computer-generated block randomisation algorithm, stratified by hospital location in Scotland vs. England/Wales) to one of 12 months in which the intervention would be delivered. All sites began in the control state. The intervention was delivered by a recruitment co-ordinator via a teleconference with each site. The intervention involved discussing recruitment strategies, providing software for each site to extract from their own stroke audit data lists of patients who were potentially eligible for RESTART, and a second teleconference to review progress 6 months later. The recruitment co-ordinator was blinded to the timing of the intervention until 2 months before it was due at a site. Staff at RESTART sites were blinded to the nature and timing of the intervention. The primary outcome is the total number of patients randomised into RESTART per month per site and will be analysed in a negative binomial generalised linear mixed model. PRIME began in September 2015. The last intervention was delivered in August 2016. Six-month follow-up will be complete in February 2017. DISCUSSION: The final results of PRIME will be analysed and disseminated in 2017. TRIAL REGISTRATION: The PRIME study was registered in the Northern Ireland Hub for Trials Methodology Research Studies Within a Trial (SWAT) repository (SWAT22) on 23 December 2015.


Assuntos
Hemorragia Cerebral/prevenção & controle , Registros Eletrônicos de Saúde , Fibrinolíticos/administração & dosagem , Gestão da Informação , Seleção de Pacientes , Inibidores da Agregação de Plaquetas/administração & dosagem , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Protocolos Clínicos , Esquema de Medicação , Fibrinolíticos/efeitos adversos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Fatores de Risco , Tamanho da Amostra , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Reino Unido
14.
Stat Methods Med Res ; 26(6): 2681-2699, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26423728

RESUMO

It is often unclear what specific adaptive trial design features lead to an efficient design which is also feasible to implement. This article describes the preparatory simulation study for a Bayesian response-adaptive dose-finding trial design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of Dexamethasone in reducing excessive menstrual bleeding and to determine the best dose for further study. To maximise learning about the dose response, patients receive placebo or an active dose with randomisation probabilities adapting based on evidence from patients already recruited. The dose-response relationship is estimated using a flexible Bayesian Normal Dynamic Linear Model. Several competing design options were considered including: number of doses, proportion assigned to placebo, adaptation criterion, and number and timing of adaptations. We performed a fractional factorial study using SAS software to simulate virtual trial data for candidate adaptive designs under a variety of scenarios and to invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial results using Normal linear models to estimate the effects of each design feature on empirical type I error and statistical power. Our readily-implemented approach using widely available statistical software identified a final design which performed robustly across a range of potential trial scenarios.


Assuntos
Ensaios Clínicos Adaptados como Assunto/estatística & dados numéricos , Teorema de Bayes , Dexametasona/administração & dosagem , Menorragia/tratamento farmacológico , Ensaios Clínicos Adaptados como Assunto/métodos , Bioestatística/métodos , Simulação por Computador , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Humanos , Modelos Lineares , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Software
15.
PLoS One ; 11(12): e0168321, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27973556

RESUMO

INTRODUCTION: The Bland-Altman limits of agreement method is widely used to assess how well the measurements produced by two raters, devices or systems agree with each other. However, mixed effects versions of the method which take into account multiple sources of variability are less well described in the literature. We address the practical challenges of applying mixed effects limits of agreement to the comparison of several devices to measure respiratory rate in patients with chronic obstructive pulmonary disease (COPD). METHODS: Respiratory rate was measured in 21 people with a range of severity of COPD. Participants were asked to perform eleven different activities representative of daily life during a laboratory-based standardised protocol of 57 minutes. A mixed effects limits of agreement method was used to assess the agreement of five commercially available monitors (Camera, Photoplethysmography (PPG), Impedance, Accelerometer, and Chest-band) with the current gold standard device for measuring respiratory rate. RESULTS: Results produced using mixed effects limits of agreement were compared to results from a fixed effects method based on analysis of variance (ANOVA) and were found to be similar. The Accelerometer and Chest-band devices produced the narrowest limits of agreement (-8.63 to 4.27 and -9.99 to 6.80 respectively) with mean bias -2.18 and -1.60 breaths per minute. These devices also had the lowest within-participant and overall standard deviations (3.23 and 3.29 for Accelerometer and 4.17 and 4.28 for Chest-band respectively). CONCLUSIONS: The mixed effects limits of agreement analysis enabled us to answer the question of which devices showed the strongest agreement with the gold standard device with respect to measuring respiratory rates. In particular, the estimated within-participant and overall standard deviations of the differences, which are easily obtainable from the mixed effects model results, gave a clear indication that the Accelerometer and Chest-band devices performed best.


Assuntos
Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Pneumologia/instrumentação , Taxa Respiratória , Acelerometria , Análise de Variância , Humanos , Fotopletismografia/métodos , Reprodutibilidade dos Testes , Respiração , Índice de Gravidade de Doença
16.
BMC Public Health ; 16(1): 1033, 2016 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-27716297

RESUMO

BACKGROUND: Very brief interventions (VBIs) for physical activity are promising, but there is uncertainty about their potential effectiveness and cost. We assessed potential efficacy, feasibility, acceptability, and cost of three VBIs in primary care, in order to select the most promising intervention for evaluation in a subsequent large-scale RCT. METHODS: Three hundred and ninety four adults aged 40-74 years were randomised to a Motivational (n = 83), Pedometer (n = 74), or Combined (n = 80) intervention, delivered immediately after a preventative health check in primary care, or control (Health Check only; n = 157). Potential efficacy was measured as the probability of a positive difference between an intervention arm and the control arm in mean physical activity, measured by accelerometry at 4 weeks. RESULTS: For the primary outcome the estimated effect sizes (95 % CI) relative to the Control arm for the Motivational, Pedometer and Combined arms were respectively: +20.3 (-45.0, +85.7), +23.5 (-51.3, +98.3), and -3.1 (-69.3, +63.1) counts per minute. There was a73% probability of a positive effect on physical activity for each of the Motivational and Pedometer VBIs relative to control, but only 46 % for the Combined VBI. Only the Pedometer VBI was deliverable within 5 min. All VBIs were acceptable and low cost. CONCLUSIONS: Based on the four criteria, the Pedometer VBI was selected for evaluation in a large-scale trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02863077 . Retrospectively registered 05/10/2012.


Assuntos
Exercício , Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Atenção Primária à Saúde , Actigrafia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Resultado do Tratamento
18.
PLoS Med ; 13(7): e1002098, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27458809

RESUMO

BACKGROUND: Self-monitoring of blood glucose among people with type 2 diabetes not treated with insulin does not appear to be effective in improving glycemic control. We investigated whether health professional review of telemetrically transmitted self-monitored glucose results in improved glycemic control in people with poorly controlled type 2 diabetes. METHODS AND FINDINGS: We performed a randomized, parallel, investigator-blind controlled trial with centralized randomization in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated hemoglobin (HbA1c) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice-weekly morning and evening glucose for review by family practice clinicians who were not blinded to allocation group. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycemic or blood pressure control. HbA1c assessed at 9 mo was the primary outcome. Intention-to-treat analyses were performed. 160 people were randomized to the intervention group and 161 to the usual care group between June 6, 2011, and July 19, 2013. HbA1c data at follow-up were available for 146 people in the intervention group and 139 people in the control group. The mean (SD) HbA1c at follow-up was 63.0 (15.5) mmol/mol in the intervention group and 67.8 (14.7) mmol/mol in the usual care group. For primary analysis, adjusted mean HbA1c was 5.60 mmol/mol / 0.51% lower (95% CI 2.38 to 8.81 mmol/mol/ 95% CI 0.22% to 0.81%, p = 0·0007). For secondary analyses, adjusted mean ambulatory systolic blood pressure was 3.06 mmHg lower (95% CI 0.56-5.56 mmHg, p = 0.017) and mean ambulatory diastolic blood pressure was 2.17 mmHg lower (95% CI 0.62-3.72, p = 0.006) among people in the intervention group when compared with usual care after adjustment for baseline differences and minimization strata. No significant differences were identified between groups in weight, treatment pattern, adherence to medication, or quality of life in secondary analyses. There were few adverse events and these were equally distributed between the intervention and control groups. In secondary analysis, there was a greater number of telephone calls between practice nurses and patients in the intervention compared with control group (rate ratio 7.50 (95% CI 4.45-12.65, p < 0.0001) but no other significant differences between groups in use of health services were identified between groups. Key limitations include potential lack of representativeness of trial participants, inability to blind participants and health professionals, and uncertainty about the mechanism, the duration of the effect, and the optimal length of the intervention. CONCLUSIONS: Supported telemonitoring resulted in clinically important improvements in control of glycaemia in patients with type 2 diabetes in family practice. Current Controlled Trials, registration number ISRCTN71674628. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 71674628.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Telemedicina/métodos , Telemetria , Adulto , Idoso , Idoso de 80 Anos ou mais , Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Telemetria/métodos
19.
Eur Urol Focus ; 2(2): 158-171, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28723532

RESUMO

CONTEXT: In the absence of randomised controlled trials comparing the oncologic, toxicity, and functional outcomes of salvage radical prostatectomy (SRP), salvage high-intensity focused ultrasound (SHIFU), salvage brachytherapy (SBT), and salvage cryotherapy (SCT), controversy exists as to the optimal salvage modality in radiorecurrent prostate cancer. OBJECTIVE: We carried out a meta-regression analysis to determine whether there is a difference in oncologic, toxicity, and functional outcomes using data from original publications of salvage modalities in the postradiation setting. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline citations according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We included 63 articles in the analysis (25 on SRP, 8 on SHIFU, 16 on SCT, 14 on SBT). EVIDENCE SYNTHESIS: Median values of the following variables were extracted from each study: patient age, length of follow-up, prostate-specific antigen (PSA) before radiotherapy (RT), PSA before salvage therapy, Gleason score before RT, and time interval between RT and salvage therapy. Functional, toxicity, and oncologic outcomes were measured according to rates of impotence, incontinence, fistula formation, urethral strictures, and biochemical recurrence. Meta-regression adjusting for confounders found no significant difference in oncologic outcomes between SRP and nonsurgical salvage modalities. SBT, SCT, and SHIFU appeared to have better continence outcomes than SRP. No significant difference in toxicity outcomes between modalities was found, although limitations such as reporting, selection, and publication bias and between-study heterogeneity must also be considered with these conclusions. CONCLUSIONS: Oncologic outcomes are comparable for SRP and all three nonsurgical salvage modalities. We found no significant differences in toxicity outcomes among modalities; however, SRP appears to be associated with worse rates of urinary incontinence than SBT, SCT, and SHIFU. PATIENT SUMMARY: We performed a meta-regression analysis to compare oncologic, functional, and toxicity outcomes between salvage radical prostatectomy and nonsurgical salvage modalities. Oncologic and toxicity outcomes appear to be similar; however, all nonsurgical salvage modalities may be associated with better continence outcomes.

20.
Palliat Med ; 30(5): 504-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26494368

RESUMO

BACKGROUND: The dyspnea accompanying advanced cardiorespiratory disease is often refractory to palliation. It is disabling, distressing and associated with the diseases most common everywhere in the world. The hand-held fan, used to generate a draught across the face, is a simple, cost-effective, safe, and universally applicable palliative breathlessness intervention, consistently described as valuable in qualitative research. A previous crossover trial confirmed its benefit in patients breathless at rest, but the washout period was uncertain. AIM: To determine the washout period after use of the hand-held fan to inform accurate randomized controlled trial design. DESIGN: An observational methodological study. Breathlessness intensity was measured using 100 mm visual analog scale and numerical rating scale, and "relief of breathlessness" was measured on a 5-point scale. Those benefitting from the fan provided visual analog scale/numerical rating scale scores until (1) scores returned to baseline values or (2) until response had plateaued. The primary outcome measure was the time (in minutes) to reach either component of the primary study endpoint. SETTINGS/PARTICIPANTS: Four in-/out-patient hospice/hospital units; participants had chronic refractory breathlessness using the fan. RESULTS: Overall, 31 patients participated (mean age: 74.8 years; range: 49-98 years, standard deviation = 11.5 years); 64% were males. Approximately, half of the sample experienced benefit of moderate effect size. The relative reduction in breathlessness relative to the mean baseline score for the sample was 27% for the visual analog scale and 19% for the numerical rating scale. CONCLUSION: Feasibility work is essential, even for simple widely employed interventions.


Assuntos
Dispneia/terapia , Ventilação/instrumentação , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Hospitais para Doentes Terminais , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados (Cuidados de Saúde) , Cuidados Paliativos
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