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[This corrects the article DOI: 10.1177/20458940211053196.].
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RATIONALE: Disturbances in dynamic cerebral autoregulation after ischemic stroke may have important implications for prognosis. Recent meta-analyses have been hampered by heterogeneity and small samples. AIM AND/OR HYPOTHESIS: The aim of study is to undertake an individual patient data meta-analysis (IPD-MA) of dynamic cerebral autoregulation changes post-ischemic stroke and to determine a predictive model for outcome in ischemic stroke using information combined from dynamic cerebral autoregulation, clinical history, and neuroimaging. SAMPLE SIZE ESTIMATES: To detect a change of 2% between categories in modified Rankin scale requires a sample size of â¼1500 patients with moderate to severe stroke, and a change of 1 in autoregulation index requires a sample size of 45 healthy individuals (powered at 80%, α = 0.05). Pooled estimates of mean and standard deviation derived from this study will be used to inform sample size calculations for adequately powered future dynamic cerebral autoregulation studies in ischemic stroke. METHODS AND DESIGN: This is an IPD-MA as part of an international, multi-center collaboration (INFOMATAS) with three phases. Firstly, univariate analyses will be constructed for primary (modified Rankin scale) and secondary outcomes, with key co-variates and dynamic cerebral autoregulation parameters. Participants clustering from within studies will be accounted for with random effects. Secondly, dynamic cerebral autoregulation variables will be validated for diagnostic and prognostic accuracy in ischemic stroke using summary receiver operating characteristic curve analysis. Finally, the prognostic accuracy will be determined for four different models combining clinical history, neuroimaging, and dynamic cerebral autoregulation parameters. STUDY OUTCOME(S): The outcomes for this study are to determine the relationship between clinical outcome, dynamic cerebral autoregulation changes, and baseline patient demographics, to determine the diagnostic and prognostic accuracy of dynamic cerebral autoregulation parameters, and to develop a prognostic model using dynamic cerebral autoregulation in ischemic stroke. DISCUSSION: This is the first international collaboration to use IPD-MA to determine prognostic models of dynamic cerebral autoregulation for patients with ischemic stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/complicaciones , Homeostasis , Humanos , Neuroimagen , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
OBJECTIVE: The gain and phase of the arterial blood pressure (BP)-cerebral blood flow velocity (CBFV) relationship, assessed by transfer function analysis (TFA), are widely used dynamic cerebral autoregulation (CA) metrics, but their reliability depend on the statistical significance of the magnitude squared coherence (MSC) function. We tested a new approach, based on inter-subject data, to estimate the confidence limits of MSC. APPROACH: Five minute beat-to-beat time series of mean arterial BP (MAP, Finometer) and CBFV (transcranial Doppler) were used for intra-subject (MAP and CBFV from same subject) and inter-subject (BP and CBFV swapped between subjects) estimates of MSC. The 95% confidence limit of MSC was obtained by non-parametric methods for the cases of single frequency harmonics in the range (0.02-0.50 Hz), and also from the mean value of all possible frequency intervals in this range. MAIN RESULTS: Intra-subject estimates of MSC were obtained from 100 healthy subjects (48 female, age range: 21-82 years old) allowing calculation of 9900 inter-subject estimates, with 95% confidence limits in excellent agreement with classical values derived from surrogate random data. Confidence limits of MSC, derived from mean values, decreased asymptotically to around 0.16 with the increasing number of harmonics averaged. SIGNIFICANCE: Replacing estimates of MSC at a single frequency harmonic by the mean calculated over the range (0.02-0.30 Hz) could lead to more robust studies of dynamic CA with greater acceptance of recordings, an important consideration in clinical studies where measurements tend to be more susceptible to noise and artefacts.
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Circulación Cerebrovascular/fisiología , Homeostasis , Adulto , Anciano , Anciano de 80 o más Años , Presión Arterial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
OBJECTIVE: Cerebral blood flow (CBF) is influenced by changes in arterial CO2 (PaCO2). Recently, cerebral haemodynamic parameters were demonstrated to follow a four parameter logistic curve offering simultaneous assessment of dCA and CO2 vasoreactivity. However, the effects of sex on cerebral haemodynamics have yet to be described over a wide range of PaCO2. APPROACH: CBF velocity (CBFV, transcranial Doppler), blood pressure (BP, Finometer) and end-tidal CO2 (EtCO2, capnography) were measured in healthy volunteers at baseline, and in response to hypo- (-5 mmHg and -10 mmHg below baseline) and hypercapnia (5% and 8% CO2), applied in random order. MAIN RESULTS: Forty-five subjects (19 male, 26 female, mean age 37.5 years) showed significant differences between males and females in CBFV (50.9 ± 10.4 versus 61.5 ± 12.3 cm · s-1, p = 0.004), EtCO2 (39.2 ± 2.8 versus 36.9 ± 3.0 mmHg, p = 0.005), RAP (1.16 ± 0.23 versus 0.94 ± 0.40 mmHg cm · s-1, p = 0.005) and systolic BP (125.2 ± 8.0 versus 114.6 ± 12.4 mmHg, p = 0.0372), respectively. Significant differences between sexes were observed in the four logistic parameters: y min, y max, k (exponential coefficient) and x (EtCO2 level) across the haemodynamic variables. Significant differences included the CBFV-EtCO2 and ARI-EtCO2 relationship; ARImin (p = 0.036) and CBFVmax (p = 0.001), respectively. Furthermore, significant differences were observed for both CrCPmin (p = 0.045) and CrCPmax (p = 0.005) and RAPmin (p < 0.001) and RAPmax (p < 0.001). SIGNIFICANCE: This is the first study to examine sex individually within the context of a multi-level CO2 protocol. The demonstration that the logistic curve parameters are influenced by sex, highlights the need to take into account sex differences between participants in both physiological and clinical studies.
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Dióxido de Carbono/metabolismo , Circulación Cerebrovascular/fisiología , Hemodinámica/fisiología , Caracteres Sexuales , Adulto , Anciano , Presión Sanguínea/fisiología , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Procesamiento de Señales Asistido por Computador , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
OBJECTIVE: Arterial CO2 (PaCO2) has a strong effect on cerebral blood flow (CBF), but its influence on CBF regulatory mechanisms and circulatory systemic variables has not been fully described over the entire physiological range of PaCO2. APPROACH: CBF velocity (CBFV, transcranial Doppler), blood pressure (BP, Finometer) and end-tidal CO2 (EtCO2, capnography) were measured in 45 healthy volunteers (19 male, mean age 37.5 years, range 21-71) at baseline, and in response to hypo- (-5 mm Hg and -10 mm Hg below baseline) and hypercapnia (5% and 8% CO2), applied in random order. MAIN RESULTS: CBFV, cerebral dynamic autoregulation index (ARI), heart rate (HR), arterial blood pressure (ABP), critical closing pressure (CrCP) and resistance-area product (RAP) changed significantly (all p < 0.0001) for hypo- and hyper-capnia. These parameters were shown to follow a logistic curve relationship representing a 'dose-response' curve for the effects of PaCO2 on the cerebral and systemic circulations. The four logistic model parameters describing each 'dose-response' curve were specific to each of the modelled variables (ANOVA p < 0.0001). SIGNIFICANCE: The ability to model the CBFV, ARI, HR, ABP, CrCP and RAP dependency of PaCO2 over its entire physiological range is a powerful tool for physiological and clinical studies, including the need to perform adjustments in disease populations with differing values of baseline PaCO2.
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Arterias/metabolismo , Dióxido de Carbono/metabolismo , Circulación Cerebrovascular , Hemodinámica , Modelos Biológicos , Adulto , Anciano , Arterias/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Objective The progressive rise in demand on NHS emergency care resources is partly attributable to increases in attendances of children and older people. A quality gap exists in the care provision for the old and the young. The Five Year Forward View suggested new models of care but that the "answer is not one-size-fits-all". This article discusses the urgent need for person-centred outcome measures to bridge the gap that exists between demand and provision. Design This review is based on evidence gathered from literature searching across several platforms using a variety of search terms to account for the obvious heterogeneity, drawing on key 'think-tank' evidence. Settings Qualitative and quantitative studies examining approaches to caring for individuals at the extremes of age. Participants Individuals at the extremes of age (infants and older people). Main Outcome Measures Understanding similarities and disparities in the care of individuals at the extremes of age in an emergency and non-emergency context. Results There exists several similarities and disparities in the care of individuals at the extremes of age. The increasing burden of health disease on the economy must acknowledge the challenges that exist in managing patients in emergency settings at the extremes of age and build systems to acknowledge the traits these individuals exhibit. Conclusion Commissioners of services must optimise the models of care delivery by appreciating the similarities and differences between care requirements in these two large groups seeking emergency care.
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Atención a la Salud/organización & administración , Urgencias Médicas , Servicios Médicos de Urgencia/organización & administración , Calidad de Vida , Humanos , Evaluación de Resultado en la Atención de SaludRESUMEN
Medical engagement is increasingly important in ensuring that organizations deliver safe and effective patient care. The recent wave of encouragement for junior doctors to become 'change agents' is fundamental to embedding this culture. However, the mechanisms by which junior doctors engage in complex health-care systems are not well developed. The authors describe the process of setting up a doctors in training committee and its role in a large NHS trust as a way of improving junior doctor engagement.
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Cuerpo Médico de Hospitales/organización & administración , Medicina Estatal/organización & administración , Humanos , Cuerpo Médico de Hospitales/educación , Reino UnidoRESUMEN
OBJECTIVE: PaCO2 affects cerebral blood flow (CBF) and its regulatory mechanisms, but the effects of CO2 measurement technique on cerebrovascular parameters are unknown. In order to determine if the two most commonly used approaches, face mask (FM) or nasal cannulae (NC), are interchangeable or not, we tested the hypothesis that the use of FM versus NC does not lead to significant differences in CO2-related systemic and cerebrovascular parameters. APPROACH: Recordings of CBF velocity (CBFV), blood pressure (BP), heart rate, and end-tidal CO2 (EtCO2) were performed in 42 subjects during normocapnia (FM or NC) and 5% CO2 inhalation (FM) or hyperventilation (NC). Dynamic cerebral autoregulation was assessed with the autoregulation index (ARI), derived by transfer function analysis from the CBFV response to a hypothetical step change in BP. MAIN RESULTS: Significant differences in physiological parameters were seen between FM and NC: EtCO2 (37.40 versus 35.26 mmHg, p = 0.001) and heart rate (69.6 versus 66.7 bpm, p = 0.001) respectively. No differences were observed for mean BP, CBFV or the ARI index. SIGNIFICANCE: Use of FM or NC for measurement of EtCO2 leads to physiological changes and differences in parameter values that need to be taken into consideration when interpreting and/or comparing results in studies of cerebral haemodynamics.
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Cánula , Dióxido de Carbono/metabolismo , Cara , Hemodinámica , Máscaras , Monitoreo Fisiológico/instrumentación , HumanosRESUMEN
Stroke medicine has seen rapid developments in diagnosis and management, and consequently improved prognosis. Management of ischaemic stroke, in particular, has benefited from these advances. The approach to management has evolved from one of historical passivity to active intervention with time of the essence following stroke onset. The last decade has seen the comparative effectiveness of several pharmacological agents being tested, creating significant randomised controlled trial evidence to support the management of common clinical problems following acute stroke. While several of these interventions are widely available, some remain less accessible. This review will discuss the latest developments in clinical stroke medicine, based on a symposium presentation at the Royal College of Physicians of Edinburgh, and reference key randomised controlled trial evidence in an effort to provide a balanced perspective on our current understanding of acute ischaemic and haemorrhagic stroke.
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Isquemia Encefálica/complicaciones , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapia , Enfermedad Aguda , Hemorragia Cerebral/complicaciones , Ambulación Precoz , Humanos , Hipertensión/tratamiento farmacológico , Posicionamiento del Paciente , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Trombectomía , Terapia TrombolíticaRESUMEN
OBJECTIVE: To determine if the use of sitagliptin in newly treated patients with type 2 diabetes is associated with any changes in clinical outcomes. DESIGN: Retrospective population based cohort study. SETTING: Large national commercially insured US claims and integrated laboratory database. PARTICIPANTS: Inception cohort of new users of oral antidiabetic drugs between 2004 and 2009 followed until death, termination of medical insurance, or December 31 2010. MAIN OUTCOME MEASURE: Composite endpoint of all cause hospital admission and all cause mortality, assessed with time varying Cox proportional hazards regression after adjustment for demographics, clinical and laboratory data, pharmacy claims data, healthcare use, and time varying propensity scores. RESULTS: The cohort included 72,738 new users of oral antidiabetic drugs (8032 (11%) used sitagliptin; 7293 (91%) were taking it in combination with other agents) followed for a total of 182,409 patient years. The mean age was 52 (SD 9) years, 54% (39,573) were men, 11% (8111) had ischemic heart disease, and 9% (6378) had diabetes related complications at the time their first antidiabetic drug was prescribed. 14,215 (20%) patients met the combined endpoint. Sitagliptin users showed similar rates of all cause hospital admission or mortality to patients not using sitagliptin (adjusted hazard ratio 0.98, 95% confidence interval 0.91 to 1.06), including patients with a history of ischemic heart disease (adjusted hazard ratio 1.10, 0.94 to 1.28) and those with estimated glomerular filtration rate below 60 mL/min (1.11, 0.88 to 1.41). CONCLUSIONS: Sitagliptin use was not associated with an excess risk of all cause hospital admission or death compared with other glucose lowering agents among newly treated patients with type 2 diabetes. Most patients prescribed sitagliptin in this cohort were concordant with clinical practice guidelines, in that it was used as add-on treatment.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hospitalización/estadística & datos numéricos , Hipoglucemiantes/uso terapéutico , Pirazinas/uso terapéutico , Triazoles/uso terapéutico , Investigación sobre la Eficacia Comparativa , Factores de Confusión Epidemiológicos , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/farmacología , Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/epidemiología , Guías de Práctica Clínica como Asunto , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Pirazinas/farmacología , Estudios Retrospectivos , Fosfato de Sitagliptina , Factores de Tiempo , Resultado del Tratamiento , Triazoles/farmacología , Estados Unidos/epidemiologíaRESUMEN
Water deficit during male meiosis in wheat (Triticum aestivum L.) causes pollen sterility. With a view to identifying the internal trigger for this failure, it was found that water stress specifically impairs the activities of vacuolar and cell-wall invertases in anthers prior to the arrest of pollen development. The enzymes are affected only when water deficit occurs around meiosis. Three invertase cDNAs, two encoding the cell-wall (Ivr1, Ivr3) and one the vacuolar (Ivr5) isoform, were isolated from an anther cDNA library. RNA gel-blot analysis using floral organs of well-watered plants revealed that these genes were expressed preferentially, though not exclusively, in anthers. Semi-quantitative RT-PCR demonstrated that transitory water deficit during meiosis selectively down-regulated the transcription of two of the three genes, one encoding the vacuolar (Ivr5) and the other a cell-wall (Ivr1) isoform, without affecting the Ivr3 message. Their expression did not recover upon resumption of watering. Another homologue of Ivr1 was also down-regulated, but only during the post-stress period. The stress effects on invertase transcripts were consistent with those on the developmental profiles of the corresponding enzyme activities. In situ hybridization revealed that the stress-sensitive invertase genes, unlike an insensitive one, were expressed within the microspores. No evidence for an invertase inhibitor under stress was found. Together the results show that the decline in invertase activity is probably regulated primarily at the transcriptional level in a gene- and cell-specific manner.