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1.
Ultrasound Obstet Gynecol ; 64(2): 193-202, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38207160

RESUMEN

OBJECTIVE: Fetoscopic closure of spina bifida using heated and humidified carbon dioxide gas (hhCO2) has been associated with lower maternal morbidity compared with open closure. Fetal cardiovascular changes during these surgical interventions are poorly defined. Our objective was to compare fetal bradycardia (defined as fetal heart rate (FHR) < 110 bpm for 10 min) and changes in umbilical artery (UA) Doppler parameters during open vs fetoscopic closure. METHODS: This was a prospective cohort study of 22 open and 46 fetoscopic consecutive in-utero closures conducted between 2019 and 2023. Both cohorts had similar preoperative counseling and clinical management. FHR and UA Doppler velocimetry were obtained systematically during preoperative assessment, every 5 min during the intraoperative period, and during the postoperative assessment. FHR, UA pulsatility index (PI) and UA end-diastolic flow (EDF) were segmented into hourly periods during surgery, and the lowest values were averaged for analysis. Umbilical vein maximum velocity was measured in the fetoscopic cohort. At each timepoint at which FHR was recorded, maternal heart rate and systolic and diastolic blood pressure were measured. RESULTS: Fetal bradycardia occurred in 4/22 (18.2%) cases of open closure and 21/46 (45.7%) cases of fetoscopic closure (P = 0.03). FHR decreased gradually in both cohorts after administration of general anesthesia and decreased further during surgery. FHR was significantly lower during hour 2 of surgery in the fetoscopic-repair cohort compared with the open-repair cohort. The change in FHR from baseline in the final stage of fetal surgery was significantly more pronounced in the fetoscopic-repair cohort compared with the open-repair cohort (mean, -32.4 (95% CI, -35.7 to -29.1) bpm vs -23.5 (95% CI, -28.1 to -18.8) bpm; P = 0.002). Abnormal UA-EDF (defined as absent or reversed EDF) occurred in 3/22 (13.6%) cases in the open-repair cohort and 23/46 (50.0%) cases in the fetoscopic-repair cohort (P = 0.004). There were no differences in UA-EDF or UA-PI between closure techniques at the individual stages of assessment. CONCLUSIONS: We observed a decrease in FHR and abnormalities in UA Doppler parameters during both open and fetoscopic spina bifida closure. Fetal bradycardia was more prominent during fetoscopic closure following hhCO2 insufflation, but FHR recovered after cessation of hhCO2. Changes in FHR and UA Doppler parameters during in-utero spina bifida closure were transient, no cases required emergency delivery and no fetoscopic closure was converted to open closure. These observations should inform algorithms for the perioperative management of fetal bradycardia associated with in-utero spina bifida closure. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Bradicardia , Fetoscopía , Frecuencia Cardíaca Fetal , Disrafia Espinal , Arterias Umbilicales , Humanos , Femenino , Fetoscopía/métodos , Fetoscopía/efectos adversos , Embarazo , Estudios Prospectivos , Bradicardia/etiología , Bradicardia/embriología , Adulto , Disrafia Espinal/cirugía , Disrafia Espinal/embriología , Disrafia Espinal/diagnóstico por imagen , Disrafia Espinal/fisiopatología , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/fisiopatología , Ultrasonografía Prenatal , Velocidad del Flujo Sanguíneo , Flujo Pulsátil , Feto/cirugía
2.
Anaesthesia ; 79(4): 353-356, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38173353
3.
Ultrasound Obstet Gynecol ; 60(5): 666-672, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35751885

RESUMEN

OBJECTIVE: During in-utero spina bifida (SB) repair, closure of large defects is often challenging, requiring tissue graft for watertight skin closure. No prior studies have compared primary skin closure vs patch-based repair. Our objective was to compare neonatal and 1-year outcomes associated with these two types of skin closure for in-utero SB repair. METHODS: This was a prospective cohort study of 102 patients undergoing open prenatal SB repair from September 2011 to August 2021 at a single institution. All patients met the inclusion criteria of the Management of Myelomeningocele Study (MOMS), and the surgical procedure for in-utero SB repair was similar to that described in the MOMS trial. During the surgery, if primary skin approximation was not feasible due to the large size of the defect, the decision was at the discretion of the pediatric neurosurgeon to utilize a patch for closure. Neonatal outcomes at birth and 1-year outcomes were compared between the primary skin and patch-based closure groups. RESULTS: Of 102 patients included in the study, 70 (68.6%) underwent primary skin closure and 32 (31.4%) patch-based closure. The patch type included acellular bovine skin matrix (Durepair®; n = 31) and human acellular dermal matrix (Alloderm®; n = 1). Fetuses with myeloschisis were more likely to require patch-based repair than those with myelomeningocele. The median time of fetal repair was 4 min longer for patch-based compared with primary skin closure (37 vs 33 min; P = 0.001). Following patch-based repair, neonates had a longer length of stay in the neonatal intensive care unit (NICU) by 24 days (adjusted risk ratio, 2.40 (95% CI, 1.41-4.29)) compared to those that underwent primary skin closure. There was no difference between the two groups in the other neonatal outcomes, including the need for ventriculoperitoneal shunt placement and cerebrospinal fluid leakage. Outcome at 1 year of age was available for 90 infants. Need for wound revision within their first year after birth was more common in infants who underwent patch-based vs those with primary skin closure (19.4% vs 5.1%; P = 0.05). There was no difference between the two groups in other 1-year outcomes, including the need for ventriculoperitoneal shunt placement by 1 year of age and surgery for tethered cord. CONCLUSIONS: Patch-based closure during SB repair is often needed in fetuses with myeloschisis and is associated with prolonged fetal surgery time, long NICU stay and need for wound revision within the first year after birth. Further studies are required to identify optimal patches for SB repair or alternative methods to improve outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Meningomielocele , Espina Bífida Quística , Embarazo , Lactante , Femenino , Humanos , Animales , Bovinos , Niño , Meningomielocele/cirugía , Estudios Prospectivos , Edad Gestacional , Derivación Ventriculoperitoneal , Espina Bífida Quística/cirugía
4.
Int J Psychiatry Med ; 57(2): 91-102, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-33892599

RESUMEN

BACKGROUND: Patients with depressive symptoms are common in primary care. Brief, simple therapies are needed. AIM: Is a focussed acceptance and commitment therapy (FACT) intervention more effective than the control group for patients with depressive symptoms in primary care at one week follow up?Design and setting: A randomised, blinded controlled trial at a single primary care clinic in Auckland, New Zealand. METHODS: Patients presenting to their primary care practice for any reason were recruited from the clinic waiting room. Eligible patients who scored ≥2 on the PHQ-2 indicating potential depressive symptoms were randomised using a remote computer to intervention or control groups. Both groups received a psychosocial assessment using the "work-love-play" questionnaire. The intervention group received additional FACT-based behavioural activation activities. The primary outcome was the mean PHQ-8 score at one week. RESULTS: 57 participants entered the trial and 52 had complete outcome data after one week. Baseline PHQ-8 scores were similar for intervention (11.0) and control (11.7). After one week, the mean PHQ-8 score was significantly lower in the intervention group (7.4 vs 10.1 for control; p<0.039 one sided and 0.078 two sided). The number needed to treat to achieve a PHQ-8 score ≤6 was 4.0 on intention to treat analysis (p = 0.043 two sided). There were no significant differences observed on the secondary outcomes. CONCLUSION: This is the first effectiveness study to examine FACT in any population. The results suggest that it is effective compared with control, at one week, for patients with depressive symptoms in primary care.


Asunto(s)
Terapia de Aceptación y Compromiso , Análisis Costo-Beneficio , Depresión/psicología , Depresión/terapia , Humanos , Nueva Zelanda , Atención Primaria de Salud , Encuestas y Cuestionarios , Resultado del Tratamiento
5.
Anaesthesia ; 76(1): 19-26, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32406071

RESUMEN

Over 30,000 adult cardiac operations are carried out in the UK annually. A small number of these patients need to return to theatre in the first few days after the initial surgery, but the exact proportion is unknown. The majority of these resternotomies are for bleeding or cardiac tamponade. The Association of Cardiothoracic Anaesthesia and Critical Care carried out a 1-year national audit of resternotomy in 2018. Twenty-three of the 35 centres that were eligible participated. The overall resternotomy rate (95%CI) within the period of admission for the initial operation in these centres was 3.6% (3.37-3.85). The rate varied between centres from 0.69% to 7.6%. Of the 849 patients who required resternotomy, 127 subsequently died, giving a mortality rate (95%CI) of 15.0% (12.7-17.5). In patients who underwent resternotomy, the median (IQR [range]) length of stay on ICU was 5 (2-10 [0-335]) days, and time to tracheal extubation was 20 (12-48 [0-2880]) hours. A total of 89.3% of patients who underwent resternotomy were transfused red cells, with a median (IQR [range]) of 4 (2-7 [1-1144]) units of red blood cells. The rate (95%CI) of needing renal replacement therapy was 23.4% (20.6-26.5). This UK-wide audit has demonstrated that resternotomy after cardiac surgery is associated with prolonged intensive care stay, high rates of blood transfusion, renal replacement therapy and very high mortality. Further research into this area is required to try to improve patient care and outcomes in patients who require resternotomy in the first 24 h after cardiac surgery.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/mortalidad , Procedimientos Quirúrgicos Cardíacos/estadística & datos numéricos , Reoperación/mortalidad , Reoperación/estadística & datos numéricos , Esternotomía/mortalidad , Esternotomía/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Extubación Traqueal , Taponamiento Cardíaco/etiología , Taponamiento Cardíaco/cirugía , Cuidados Críticos/estadística & datos numéricos , Transfusión de Eritrocitos/mortalidad , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Humanos , Incidencia , Tiempo de Internación , Masculino , Auditoría Médica , Persona de Mediana Edad , Hemorragia Posoperatoria/cirugía , Terapia de Reemplazo Renal/mortalidad , Terapia de Reemplazo Renal/estadística & datos numéricos , Reino Unido/epidemiología
6.
J Opt Soc Am A Opt Image Sci Vis ; 37(12): 1950-1957, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33362138

RESUMEN

Monitoring strain is important in precision engineering applications that require maintaining the precise alignments of structures over time, such as those found in machine tools and metrology frames. We present a fiber-optic strain measurement technique based upon broadband interferometry that is variously configurable in terms of gauge length and sensitivity. This is achieved by the use of an unbalanced interrogation interferometer configuration that alleviates the cavity length limit imposed by the temporal coherence of the system. We also demonstrate that dispersion in fiber sensors based on intrinsic Fabry-Perot interferometers must be considered to optimize performance. The possibility of multisensor interrogation using the same optical system is also reported.

8.
Anaesthesia ; 75(5): 654-663, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32017012

RESUMEN

These guidelines aim to ensure that patients with adrenal insufficiency are identified and adequately supplemented with glucocorticoids during the peri-operative period. There are two major categories of adrenal insufficiency. Primary adrenal insufficiency is due to diseases of the adrenal gland (failure of the hormone-producing gland), and secondary adrenal insufficiency is due to deficient adrenocorticotropin hormone secretion by the pituitary gland, or deficient corticotropin-releasing hormone secretion by the hypothalamus (failure of the regulatory centres). Patients taking physiological replacement doses of corticosteroids for either primary or secondary adrenal insufficiency are at significant risk of adrenal crisis and must be given stress doses of hydrocortisone during the peri-operative period. Many more patients other than those with adrenal and hypothalamic-pituitary causes of adrenal failure are receiving glucocorticoids as treatment for other medical conditions. Daily doses of prednisolone of 5 mg or greater in adults and 10-15 mg.m-2 hydrocortisone equivalent or greater in children may result in hypothalamo-pituitary-adrenal axis suppression if administered for 1 month or more by oral, inhaled, intranasal, intra-articular or topical routes; this chronic administration of glucocorticoids is the most common cause of secondary adrenal suppression, sometimes referred to as tertiary adrenal insufficiency. A pragmatic approach to adrenal replacement during major stress is required; considering the evidence available, blanket recommendations would not be appropriate, and it is essential for the clinician to remember that adrenal replacement dosing following surgical stress or illness is in addition to usual steroid treatment. Patients with previously undiagnosed adrenal insufficiency sometimes present for the first time following the stress of surgery. Anaesthetists must be familiar with the symptoms and signs of acute adrenal insufficiency so that inadequate supplementation or undiagnosed adrenal insufficiency can be detected and treated promptly. Delays may prove fatal.


Asunto(s)
Insuficiencia Suprarrenal/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Atención Perioperativa/métodos , Insuficiencia Suprarrenal/epidemiología , Insuficiencia Suprarrenal/fisiopatología , Adulto , Niño , Glucocorticoides/efectos adversos , Glucocorticoides/farmacología , Guías como Asunto , Humanos , Prevalencia , Resultado del Tratamiento , Reino Unido
9.
Ultrasound Obstet Gynecol ; 56(5): 678-683, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31763720

RESUMEN

OBJECTIVES: Fetal surgery for repair of open neural tube defect (ONTD) typically results in decreased need for a ventriculoperitoneal shunt (VPS). Our objectives were to determine the trend in ventricle size (VS) during pregnancy and whether VS and change in VS, as assessed by ultrasound, were predictive of the need for VPS in pregnancy with ONTD. METHODS: This was a retrospective analysis of prospectively collected data of consecutive pregnancies with ONTD, evaluated in a single center from January 2012 to May 2018. Two groups were identified: the first consisted of pregnancies that underwent in-utero repair (IUR) and the second those that had postnatal repair (PNR). Penalized B splines were used to determine the trend in VS, across 2-week gestational-age (GA) epochs, between 24 and 36 weeks of gestation. VS at each GA epoch and the change in VS between each GA epoch were compared between the IUR and PNR groups. To determine whether VS at any GA was predictive of VPS, receiver-operating-characteristics (ROC) curves were used and the optimal cut-off at each GA epoch was identified. Univariate analysis and multiple logistic regression were used for further analysis. RESULTS: ONTD was diagnosed in 110 fetuses, of whom 69 underwent IUR and 41 had PNR. Fetuses in the IUR group were more likely to have Chiari II malformation (100.0% vs 82.9%; P < 0.01), lower GA at delivery (34.9 ± 3.2 vs 37.1 ± 2.1 weeks; P < 0.01) and lower rates of VPS within the first year postpartum (36.2% vs 61.0%; P = 0.02) compared with the PNR group. In both groups, VS increased steadily with GA from the initial evaluation to delivery. In the IUR group, there was a significant change in VS between the 24 + 0 to 25 + 6-week and the 26 + 0 to 27 + 6-week epochs (2.3 (95% CI, 0.4-4.1) mm; P = 0.02). There was a positive trend in the change in VS at later GAs, but this was not significant. Although there was no significant change in VS in the PNR group before 30 weeks, there was a positive trend after that time. On multivariate analysis, each week of advancing GA was associated with a mean increase of 0.74 mm in VS (P < 0.0001) in both groups. VS was not associated with the level or type of lesion, but presence of Chiari II malformation was associated with a mean increase of 5.88 mm (P < 0.0001) in VS in both the IUR and PNR groups. VS was modestly predictive of need for VPS in both groups, with area under ROC curves between 0.68 and 0.76 at the different GA epochs. Change in VS between the first and last measurements was also modestly predictive of the need for VPS, with better performance in the PNR group. CONCLUSIONS: VS increased with advancing GA in all fetuses with ONTD, although in the IUR group this increase occurred immediately after fetal surgery and in the PNR group it occurred after 30 weeks of gestation. In-utero surgery was associated with a decreased rate of VPS and was more predictive of need for VPS than was VS. Postnatal factors resulting in increased need for VPS in the PNR group need to be assessed further. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Asunto(s)
Ventrículos Cerebrales/diagnóstico por imagen , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/cirugía , Ultrasonografía Prenatal/estadística & datos numéricos , Derivación Ventriculoperitoneal/estadística & datos numéricos , Adulto , Ventrículos Cerebrales/embriología , Femenino , Terapias Fetales/estadística & datos numéricos , Edad Gestacional , Humanos , Lactante , Recién Nacido , Defectos del Tubo Neural/embriología , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Curva ROC , Estudios Retrospectivos , Resultado del Tratamiento
10.
Appl Radiat Isot ; 156: 108951, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31790976

RESUMEN

With the advancement of high-precision radiotherapy and the increasing use of higher intensity beams, the risk to the patient increases should the radiotherapy machine malfunction. Hence more accurate treatment verification is required. In this paper we provide a solution for real-time monitoring of X-ray beams from radiotherapy linear accelerators using monolithic active pixel sensors. We show that leaf errors can be detected with high precision in static fields and IMRT step and shoot, and accurate leaf tracking is possible in Volumetric Modulated Arc Therapy. The prototype MAPS detector meets the criteria of 1% attenuation acceptable for clinical use.


Asunto(s)
Radioterapia de Intensidad Modulada/métodos , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Silicio/química
11.
Anaesthesia ; 75(1): 21-26, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31236918

RESUMEN

Previous studies on the safety of peri-operative transoesophageal echocardiography seem to suggest a low rate of associated morbidity and mortality. That said, there has been a paucity of prospective multicentre studies in this important area of clinical practice. We carried out a one-year prospective study in 2017, co-ordinated by the Association of Cardiothoracic Anaesthesia and Critical Care, to determine the rate and severity of complications associated with peri-operative transoesophageal echocardiography in anaesthetised cardiology and cardiac surgical patients. With the help of clinicians from 28 centres across the UK and Ireland, we recorded the total number of examinations conducted in anaesthetised patients during the study period. All major complications at each centre were prospectively reported and recorded. Of the 22,314 examinations, there were 17 patients diagnosed with a major complication which caused either palatal injury or gastro-oesophageal disruption. This corresponds to an incidence of 0.08% (95%CI 0.05-0.13%) or approximately 1:1300 examinations. There were seven deaths reported during the study period which were directly attributed to these complications, corresponding to an incidence of 0.03% (95%CI 0.01-0.07%) or approximately 1:3000. These figures are higher than previously reported and suggest a high probability of death following the development of a complication (~40%). Most complications occurred in patients without known risk factors for transoesophageal echocardiography associated gastro-oesophageal injury. We suggest clinicians and departments review their procedural guidelines, especially in relation to probe insertion techniques, together with the information communicated to patients when the risks and benefits of such examinations are discussed.


Asunto(s)
Anestesia en Procedimientos Quirúrgicos Cardíacos , Procedimientos Quirúrgicos Cardíacos , Ecocardiografía Transesofágica/efectos adversos , Auditoría Médica/estadística & datos numéricos , Atención Perioperativa/efectos adversos , Anciano , Ecocardiografía Transesofágica/estadística & datos numéricos , Femenino , Humanos , Irlanda , Masculino , Atención Perioperativa/métodos , Atención Perioperativa/estadística & datos numéricos , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sociedades Médicas , Reino Unido
12.
Acta Neuropathol Commun ; 7(1): 30, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30823891

RESUMEN

TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knock-in mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation.


Asunto(s)
Senescencia Celular/fisiología , Desarrollo de Músculos/fisiología , Enfermedades Musculares/genética , Enfermedades Musculares/patología , Mioblastos/patología , Factores de Transcripción/genética , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Anciano , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Musculares/metabolismo , Mioblastos/metabolismo , Linaje , Factores de Transcripción/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
13.
J Intensive Care Soc ; 20(1): 11-17, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30792757

RESUMEN

Metabolic acidosis is considered deleterious but is common in post-surgical patients admitted to intensive care unit. We evaluated the prevalence and time course of metabolic acidosis in elective major surgery, and generated hypotheses about causes, by hourly arterial blood sampling in 92 patients. Metabolic acidosis began before incision and most had occurred by the next hour. Seventy-eight per cent of patients had a significant metabolic acidosis post-operatively. Two overlapping phases were observed. The early phase started before incision, characterised by a rising chloride and falling anion gap, unrelated to saline use. The late phase was partly associated with lactate, related to surgery type, and early fluids appeared protective. There was a trend towards longer intensive care unit (+1.3 days) and hospital (+3.2 days) stay with metabolic acidosis. This is the first large study of the evolution of this common finding, demonstrating a pre-incision component. The early phase appears unavoidable or unpredictable, but the late phase might be modified by early fluid administration. It remains unclear whether acidosis of this type should be avoided.

14.
Appl Ergon ; 74: 1-9, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30487087

RESUMEN

Human visual inspection skills remain superior for ensuring product quality and conformance to standards in the manufacturing industry. However, at present these skills cannot be formally shared with other workers or used to develop and implement new solutions or assistive technologies because they involve a high level of tacit knowledge which only exists in skilled operators' internal cognitions. Industry needs reliable methods for the capture and analysis of this tacit knowledge so that it can be shared and not lost but also so that it can be best utilised in the transfer of manual work to automated systems and introduction of new technologies and processes. This paper describes two UK manufacturing case studies that applied systematic task analysis methods to capture and scrutinise the tacit knowledge and skills being applied in the visual inspection of aerospace components. Results reveal that the method was effective in eliciting tacit knowledge, and showed that tacit skills are particularly needed when visual inspection standards lack specification or the task requires greater subjective interpretation. The implications of these findings for future research and for developments in the manufacturing industry are discussed.


Asunto(s)
Ergonomía/métodos , Análisis y Desempeño de Tareas , Adulto , Femenino , Humanos , Conocimiento , Masculino , Instalaciones Industriales y de Fabricación
15.
Neuropharmacology ; 135: 284-296, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29578034

RESUMEN

S 47445 is a positive modulator of glutamate AMPA-type receptors, possessing neurotrophic and enhancing synaptic plasticity effects as well as pro-cognitive and anti-stress properties. Here, the drug was assessed in the perinatal stress (PRS) rat model, known to have a high predictive validity with monoaminergic antidepressants. The effects of a chronic treatment (i.p.) with S 47445 were investigated on risk-taking, motivational and cognitive behavior. S 47445 (1 and 10 mg/kg) increased the exploration of the elevated-plus maze and light/dark box as well as the time spent grooming in the splash test, and improved social memory in PRS rats. Also, the effects of S 47445 were examined on the synaptic neurotransmission. The reduced depolarization-evoked glutamate release induced by PRS was corrected with S 47445 (10 mg/kg). Remarkably, the reduction in glutamate release induced by PRS and corrected by S 47445 chronic treatment was correlated with all the behavioral changes. S 47445 at 10 mg/kg also normalized the lower levels of synaptic vesicle-associated proteins in ventral hippocampus in PRS rats. Finally, S 47445 reversed the decrease of mGlu5 receptors, GR and OXTR induced by PRS. Collectively, in an animal model of stress-related disorders, S 47445 corrected the imbalance between excitatory and inhibitory neurotransmission by regulating glutamate-evoked release that is predictive of PRS behavioral alterations, and also normalized the reduction of trafficking of synaptic vesicles induced by PRS. These results support the interest of glutamatergic-based therapeutic strategies to alleviate stress-related disorders.


Asunto(s)
Benzoxazinas/farmacología , Cognición/efectos de los fármacos , Emociones/efectos de los fármacos , Ácido Glutámico/metabolismo , Efectos Tardíos de la Exposición Prenatal/prevención & control , Estrés Psicológico/metabolismo , Triazinas/farmacología , Animales , Femenino , Hipocampo/metabolismo , Masculino , Proteínas del Tejido Nervioso/metabolismo , Embarazo , Ratas , Receptor del Glutamato Metabotropico 5/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Oxitocina/metabolismo
16.
J Med Screen ; 25(2): 88-98, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-28530513

RESUMEN

Objectives To measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women. Methods A two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking. In Phase 2, non-attenders at six months were randomized to one of: vaginal self-sample kits sent unrequested or offered; timed appointments; nurse navigator; or the choice between nurse navigator or self-sample kits. Primary outcome was uplift in intervention vs. control practices, at 3 and 12 months post invitation. Results Phase 1 randomized 20,879 women. Neither pre-invitation leaflet nor online booking increased screening uptake by three months (18.8% pre-invitation leaflet vs. 19.2% control and 17.8% online booking vs. 17.2% control). Uptake was higher amongst human papillomavirus vaccinees at three months (OR 2.07, 95% CI 1.69-2.53, p < 0.001). Phase 2 randomized 10,126 non-attenders, with 32-34 clusters for each intervention and 100 clusters as controls. Sending self-sample kits increased uptake at 12 months (OR 1.51, 95% CI 1.20-1.91, p = 0.001), as did timed appointments (OR 1.41, 95% CI 1.14-1.74, p = 0.001). The offer of a nurse navigator, a self-sample kits on request, and choice between timed appointments and nurse navigator were ineffective. Conclusions Amongst non-attenders, self-sample kits sent and timed appointments achieved an uplift in screening over the short term; longer term impact is less certain. Prior human papillomavirus vaccination was associated with increased screening uptake.


Asunto(s)
Detección Precoz del Cáncer , Infecciones por Papillomavirus/prevención & control , Participación del Paciente , Neoplasias del Cuello Uterino/prevención & control , Frotis Vaginal/estadística & datos numéricos , Adulto , Inglaterra , Femenino , Humanos , Lactante , Persona de Mediana Edad , Papillomaviridae/inmunología , Infecciones por Papillomavirus/diagnóstico , Vacunas contra Papillomavirus/administración & dosificación , Medicina Estatal , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico , Adulto Joven
17.
18.
Br J Anaesth ; 119(3): 394-401, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28969306

RESUMEN

BACKGROUND: A simple and accurate scoring system to predict risk of transfusion for patients undergoing cardiac surgery is lacking. METHODS: We identified independent risk factors associated with transfusion by performing univariate analysis, followed by logistic regression. We then simplified the score to an integer-based system and tested it using the area under the receiver operator characteristic (AUC) statistic with a Hosmer-Lemeshow goodness-of-fit test. Finally, the scoring system was applied to the external validation dataset and the same statistical methods applied to test the accuracy of the ACTA-PORT score. RESULTS: Several factors were independently associated with risk of transfusion, including age, sex, body surface area, logistic EuroSCORE, preoperative haemoglobin and creatinine, and type of surgery. In our primary dataset, the score accurately predicted risk of perioperative transfusion in cardiac surgery patients with an AUC of 0.76. The external validation confirmed accuracy of the scoring method with an AUC of 0.84 and good agreement across all scores, with a minor tendency to under-estimate transfusion risk in very high-risk patients. CONCLUSIONS: The ACTA-PORT score is a reliable, validated tool for predicting risk of transfusion for patients undergoing cardiac surgery. This and other scores can be used in research studies for risk adjustment when assessing outcomes, and might also be incorporated into a Patient Blood Management programme.


Asunto(s)
Transfusión Sanguínea/estadística & datos numéricos , Procedimientos Quirúrgicos Cardíacos , Reacción a la Transfusión/epidemiología , Factores de Edad , Anciano , Superficie Corporal , Creatinina/sangre , Femenino , Hemoglobinas , Humanos , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Reacción a la Transfusión/sangre
19.
PLoS One ; 12(9): e0183926, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28910330

RESUMEN

BACKGROUND: Patients with advanced chronic kidney disease (CKD) experience complex functional and structural changes of the cardiopulmonary and musculoskeletal system. This results in reduced exercise tolerance, quality of life and ultimately premature death. We investigated the relationship between subjective measures of health related quality of life and objective, standardised functional measures for cardiovascular and pulmonary health. METHODS: Between April 2010 and January 2013, 143 CKD stage-5 or CKD5d patients (age 46.0±1.1y, 62.2% male), were recruited prospectively. A control group of 83 healthy individuals treated for essential hypertension (HTN; age 53.2±0.9y, 48.22% male) were recruited at random. All patients completed the SF-36 health survey questionnaire, echocardiography, vascular tonometry and cardiopulmonary exercise testing. RESULTS: Patients with CKD had significantly lower SF-36 scores than the HTN group; for physical component score (PCS; 45.0 vs 53.9, p<0.001) and mental component score (MCS; 46.9 vs. 54.9, p<0.001). CKD subjects had significantly poorer exercise tolerance and cardiorespiratory performance compared with HTN (maximal oxygen uptake; VO2peak 19.9 vs 25.0ml/kg/min, p<0.001). VO2peak was a significant independent predictor of PCS in both groups (CKD: b = 0.35, p = 0.02 vs HTN: b = 0.27, p = 0.001). No associations were noted between PCS scores and echocardiographic characteristics, vascular elasticity and cardiac biomarkers in either group. No associations were noted between MCS and any variable. The interaction effect of study group with VO2peak on PCS was not significant (ΔB = 0.08; 95%CI -0.28-0.45, p = 0.7). However, overall for a given VO2peak, the measured PCS was much lower for patients with CKD than for HTN cohort, a likely consequence of systemic uremia effects. CONCLUSION: In CKD and HTN, objective physical performance has a significant effect on quality of life; particularly self-reported physical health and functioning. Therefore, these quality of life measures are indeed a good reflection of physical health correlating highly with objective physical performance measures.


Asunto(s)
Hipertensión/fisiopatología , Fallo Renal Crónico/fisiopatología , Calidad de Vida , Encuestas y Cuestionarios , Adulto , Electrocardiografía , Hipertensión Esencial , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
Expert Opin Biol Ther ; 17(1): 15-30, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27805416

RESUMEN

INTRODUCTION: Antisense nucleic acid analogues can interact with pre-mRNA motifs and influence exon or splice site selection and thereby alter gene expression. Design of antisense molecules to target specific motifs can result in either exon exclusion or exon inclusion during splicing. Novel drugs exploiting the antisense concept are targeting rare, life-limiting diseases; however, the potential exists to treat a wide range of conditions by antisense-mediated splice intervention. Areas covered: In this review, the authors discuss the clinical translation of novel molecular therapeutics to address the fatal neuromuscular disorders Duchenne muscular dystrophy and spinal muscular atrophy. The review also highlights difficulties posed by issues pertaining to restricted participant numbers, variable phenotype and disease progression, and the identification and validation of study endpoints. Expert opinion: Translation of novel therapeutics for Duchenne muscular dystrophy and spinal muscular atrophy has been greatly advanced by multidisciplinary research, academic-industry partnerships and in particular, the engagement and support of the patient community. Sponsors, supporters and regulators are cooperating to deliver new drugs and identify and define meaningful outcome measures. Non-conventional and adaptive trial design could be particularly suited to clinical evaluation of novel therapeutics and strategies to treat serious, rare diseases that may be problematic to study using more conventional clinical trial structures.


Asunto(s)
Exones/genética , Terapia Genética/tendencias , Distrofia Muscular de Duchenne/tratamiento farmacológico , Oligonucleótidos Antisentido/uso terapéutico , Empalme del ARN/genética , Investigación Biomédica Traslacional/métodos , Animales , Terapia Biológica/métodos , Terapia Biológica/tendencias , Distrofina/genética , Exones/efectos de los fármacos , Expresión Génica , Regulación de la Expresión Génica , Terapia Genética/métodos , Humanos , Atrofia Muscular Espinal/tratamiento farmacológico , Atrofia Muscular Espinal/genética , Distrofia Muscular de Duchenne/genética , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/farmacología , Empalme del ARN/efectos de los fármacos , Investigación Biomédica Traslacional/tendencias
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