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Foster, Katharine, James D. Anholm, Gary Foster, Suman Thapamagar, and Prajan Subedi. Effects of naltrexone on sleep quality and periodic breathing at high altitude. High Alt Med Biol. 00:000-000, 2024. Objective: This study examined the effects of naltrexone on breathing and sleep at high altitude. Mu-opioid receptor (MOR) agonists have a depressive effect on respiration. Naltrexone is known to block the MOR. We hypothesized that MOR blockade with naltrexone would result in higher nocturnal oxygen saturations, fewer apneas, and improved sleep at high altitude. Methods: This double-blind, placebo-controlled, crossover study included nine healthy volunteers (four females, five males) aged 27.9 (4.6) (mean [standard deviation]) years. Two overnight trips spaced at least 2 weeks apart took participants from Loma Linda, CA (355 m) to the Barcroft Laboratory, CA (3,810 m) for each arm. Participants ingested either 50 mg naltrexone or matching placebo at bedtime. Sleep metrics were recorded using an ambulatory physiological sleep monitor (APSM). Subjective data were measured with the Groningen Sleep Quality Scale, Stanford Sleepiness Scale, and the 2018 Lake Louise Score (LLS) for acute mountain sickness (AMS). Results: Mean overnight SpO2 was lower after taking naltrexone, 81% (6) versus 83% (4) (mean difference 1.9% [2.1, 95% confidence interval or CI = 0.1-3.6, p = 0.040]). The lowest overnight SpO2 (nadir) was lower on naltrexone 70% (6) versus 74% (4) (dif. 4.6% [4.3], CI = 1.0-8.2, p = 0.020). Total sleep time and total apnea-hypopnea index were unchanged. Subjective sleep quality was significantly worse on naltrexone measured via the Groningen Sleep Quality Scale (p = 0.033) and Stanford Sleepiness Scale (p = 0.038). AMS measured via LLS was significantly worse while taking naltrexone (p = 0.025). Conclusion: Contrary to our hypothesis, this study demonstrated a significant decrease in nocturnal oxygen saturation, worse sleep quality, and AMS scores. Further characterization of the MOR's effects on sleep and AMS is needed to evaluate potential exacerbating mechanisms for AMS and poor sleep quality at altitude.
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Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m. Participants (6 males/10 females; age, 27 ± 4 yr old) received either a placebo or 400 mg of pentoxifylline orally the night before and again 2 h before testing. We assessed arterial blood gases, venous hemorheology (blood viscosity, red blood cell deformability, and aggregation), and inflammation (TNF-α) in room air (end-tidal oxygen partial pressure, â¼52 mmHg). Global cerebral blood flow (gCBF), ventilation, and pulmonary artery systolic pressure (PASP) were measured in room air and again after 8-10 min of isocapnic hypoxia (end-tidal oxygen partial pressure, 40 mmHg). Pentoxifylline did not alter arterial blood gases, TNF-α, or hemorheology compared with placebo. Pentoxifylline did not affect gCBF or ventilation during room air or isocapnic hypoxia compared with placebo. However, in females, PASP was reduced with pentoxifylline during room air (placebo, 19 ± 3; pentoxifylline, 16 ± 3 mmHg; P = 0.021) and isocapnic hypoxia (placebo, 22 ± 5; pentoxifylline, 20 ± 4 mmHg; P = 0.029), but not in males. Acute pentoxifylline administration in lowlanders at 3,800 m had no impact on arterial blood gases, hemorheology, inflammation, gCBF, or ventilation. Unexpectedly, however, pentoxifylline reduced PASP in female participants, indicating a potential effect of sex on the pulmonary vascular responses to pentoxifylline.NEW & NOTEWORTHY We conducted a double-blind, placebo-controlled study on the rheological, cardiorespiratory and cerebrovascular effects of acute pentoxifylline in healthy lowlanders after 11-14 days at 3,800 m. Although red blood cell deformability was reduced and blood viscosity increased compared with low altitude, acute pentoxifylline administration had no impact on arterial blood gases, hemorheology, inflammation, cerebral blood flow, or ventilation. Pentoxifylline decreased pulmonary artery systolic pressure in female, but not male, participants.
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Pentoxifilina , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Pentoxifilina/farmacología , Pentoxifilina/uso terapéutico , Hemorreología , Factor de Necrosis Tumoral alfa , Hipoxia , Oxígeno , Aclimatación/fisiología , Inflamación/complicaciones , Gases , Circulación Cerebrovascular , AltitudRESUMEN
Isolated central nervous system (CNS) presentations of haemophagocytic lymphohistiocytosis (HLH), traditionally a systemic inflammatory condition, have been reported in adults and children. We identified nine patients with a diagnosis of isolated CNS familial hemophagocytic lymphohistiocytosis (fHLH) with symptom onset <18 years of age, and one asymptomatic sibling. Children with atypical chronic/recurrent CNS inflammation should be considered for immunological and genetic panel testing for fHLH even in the absence of any systemic inflammatory features. Despite haematopoietic stem cell transplantation (HSCT) being a mainstay of treatment, treatment failure and high morbidity and mortality post-HSCT suggest that alternative immune therapies may be worth considering.
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Enfermedades Desmielinizantes , Linfohistiocitosis Hemofagocítica , Adulto , Sistema Nervioso Central , Niño , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/terapiaAsunto(s)
Colágeno Tipo IV/genética , Genes Recesivos , Homocigoto , Mutación Missense , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Imagen por Resonancia Magnética , Masculino , FenotipoAsunto(s)
Asma/diagnóstico , Infecciones por Coronavirus/diagnóstico , Eccema/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Trastornos del Olfato/diagnóstico , Pandemias , Neumonía Viral/diagnóstico , Rinitis Alérgica/diagnóstico , Sinusitis/diagnóstico , Adulto , Factores de Edad , Anciano , Asma/complicaciones , Asma/epidemiología , Asma/fisiopatología , Betacoronavirus/patogenicidad , COVID-19 , Estudios de Cohortes , Comorbilidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Eccema/complicaciones , Eccema/epidemiología , Eccema/fisiopatología , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Olfato/complicaciones , Trastornos del Olfato/epidemiología , Trastornos del Olfato/fisiopatología , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Pronóstico , Rinitis Alérgica/complicaciones , Rinitis Alérgica/epidemiología , Rinitis Alérgica/fisiopatología , Medición de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Sinusitis/complicaciones , Sinusitis/epidemiología , Sinusitis/fisiopatologíaAsunto(s)
Asma/complicaciones , Betacoronavirus , Infecciones por Coronavirus/terapia , Intubación Intratraqueal , Neumonía Viral/terapia , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Factores de Tiempo , Adulto JovenRESUMEN
Retinoic acid receptor beta (RARB) variants are heavily linked to pathologies of neural crest cell migration. The purpose of this report is to present a 23-month-old male with the previously described R387C RARB gain-of-function variant whose gastrointestinal issues and long-term constipation lead to the discovery of colonic hypoganglionosis. This case further delineates the pattern of malformation associated with RARB variants. The findings are also consistent with the known etiology of aganglionic colon due to failed neural crest cell migration.
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Enfermedades Funcionales del Colon/diagnóstico , Enfermedades Funcionales del Colon/etiología , Estreñimiento/diagnóstico , Estreñimiento/etiología , Predisposición Genética a la Enfermedad , Variación Genética , Receptores de Ácido Retinoico/genética , Alelos , Exoma , Humanos , Lactante , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Mutación con Pérdida de Función , Masculino , Radiografía , Secuenciación del ExomaRESUMEN
BACKGROUND: A tool for diagnosing childhood cerebellar tumours using magnetic resonance (MR) spectroscopy peak height measurement has been developed based on retrospective analysis of single-centre data. OBJECTIVE: To determine the diagnostic accuracy of the peak height measurement tool in a multicentre prospective study, and optimise it by adding new prospective data to the original dataset. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) and single-voxel MR spectroscopy were performed on children with cerebellar tumours at three centres. Spectra were processed using standard scanner software and peak heights for N-acetyl aspartate, creatine, total choline and myo-inositol were measured. The original diagnostic tool was used to classify 26 new tumours as pilocytic astrocytoma, medulloblastoma or ependymoma. These spectra were subsequently combined with the original dataset to develop an optimised scheme from 53 tumours in total. RESULTS: Of the pilocytic astrocytomas, medulloblastomas and ependymomas, 65.4% were correctly assigned using the original tool. An optimized scheme was produced from the combined dataset correctly assigning 90.6%. Rare tumour types showed distinctive MR spectroscopy features. CONCLUSION: The original diagnostic tool gave modest accuracy when tested prospectively on multicentre data. Increasing the dataset provided a diagnostic tool based on MR spectroscopy peak height measurement with high levels of accuracy for multicentre data.
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Neoplasias Cerebelosas/diagnóstico por imagen , Espectroscopía de Resonancia Magnética/métodos , Biomarcadores de Tumor/metabolismo , Neoplasias Cerebelosas/metabolismo , Niño , Diagnóstico Diferencial , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Advances in magnetic resonance imaging and the introduction of clinical decision support systems has underlined the need for an analysis tool to extract and analyze relevant information from magnetic resonance imaging data to aid decision making, prevent errors, and enhance health care. OBJECTIVE: The aim of this study was to design and develop a modular medical image region of interest analysis tool and repository (MIROR) for automatic processing, classification, evaluation, and representation of advanced magnetic resonance imaging data. METHODS: The clinical decision support system was developed and evaluated for diffusion-weighted imaging of body tumors in children (cohort of 48 children, with 37 malignant and 11 benign tumors). Mevislab software and Python have been used for the development of MIROR. Regions of interests were drawn around benign and malignant body tumors on different diffusion parametric maps, and extracted information was used to discriminate the malignant tumors from benign tumors. RESULTS: Using MIROR, the various histogram parameters derived for each tumor case when compared with the information in the repository provided additional information for tumor characterization and facilitated the discrimination between benign and malignant tumors. Clinical decision support system cross-validation showed high sensitivity and specificity in discriminating between these tumor groups using histogram parameters. CONCLUSIONS: MIROR, as a diagnostic tool and repository, allowed the interpretation and analysis of magnetic resonance imaging images to be more accessible and comprehensive for clinicians. It aims to increase clinicians' skillset by introducing newer techniques and up-to-date findings to their repertoire and make information from previous cases available to aid decision making. The modular-based format of the tool allows integration of analyses that are not readily available clinically and streamlines the future developments.
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BACKGROUND: Pediatric retroperitoneal tumors in the renal bed are often large and heterogeneous, and their diagnosis based on conventional imaging alone is not possible. More advanced imaging methods, such as diffusion-weighted (DW) MRI and the use of intravoxel incoherent motion (IVIM), have the potential to provide additional biomarkers that could facilitate their noninvasive diagnosis. PURPOSE: To assess the use of an IVIM model for diagnosis of childhood malignant abdominal tumors and discrimination of benign from malignant lesions. STUDY TYPE: Retrospective. POPULATION: Forty-two pediatric patients with abdominal lesions (n = 32 malignant, n = 10 benign), verified by histopathology. FIELD STRENGTH/SEQUENCE: 1.5T MRI system and a DW-MRI sequence with six b-values (0, 50, 100, 150, 600, 1000 s/mm2 ). ASSESSMENT: Parameter maps of apparent diffusion coefficient (ADC), and IVIM maps of slow diffusion coefficient (D), fast diffusion coefficient (D*), and perfusion fraction (f) were computed using a segmented fitting model. Histograms were constructed for whole-tumor regions of each parameter. STATISTICAL TESTS: Comparison of histogram parameters of and their diagnostic performance was determined using Kruskal-Wallis, Mann-Whitney U, and receiver-operating characteristic (ROC) analysis. RESULTS: IVIM parameters D* and f were significantly higher in neuroblastoma compared to Wilms' tumors (P < 0.05). The ROC analysis showed that the best diagnostic performance was achieved with D* 90th percentile (area under the curve [AUC] = 0.935; P = 0.002; cutoff value = 32,376 × 10-6 mm2 /s) and f mean values (AUC = 1.00; P < 0.001; cutoff value = 14.7) in discriminating between neuroblastoma (n = 11) and Wilms' tumors (n = 8). Discrimination between tumor types was not possible with IVIM D or ADC parameters. Malignant tumors revealed significantly lower ADC, D, and higher D* values than in benign lesions (all P < 0.05). DATA CONCLUSION: IVIM perfusion parameters could distinguish between malignant childhood tumor types, providing potential imaging biomarkers for their diagnosis. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1475-1486.
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Neoplasias Abdominales/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador/métodos , Movimiento (Física) , Pediatría/métodos , Adolescente , Algoritmos , Biomarcadores/metabolismo , Niño , Preescolar , Diagnóstico por Computador , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Perfusión , Curva ROC , Estudios RetrospectivosRESUMEN
OBJECTIVES: This UK-wide study defines the natural history of argininosuccinic aciduria and compares long-term neurological outcomes in patients presenting clinically or treated prospectively from birth with ammonia-lowering drugs. METHODS: Retrospective analysis of medical records prior to March 2013, then prospective analysis until December 2015. Blinded review of brain MRIs. ASL genotyping. RESULTS: Fifty-six patients were defined as early-onset (n = 23) if symptomatic < 28 days of age, late-onset (n = 23) if symptomatic later, or selectively screened perinatally due to a familial proband (n = 10). The median follow-up was 12.4 years (range 0-53). Long-term outcomes in all groups showed a similar neurological phenotype including developmental delay (48/52), epilepsy (24/52), ataxia (9/52), myopathy-like symptoms (6/52) and abnormal neuroimaging (12/21). Neuroimaging findings included parenchymal infarcts (4/21), focal white matter hyperintensity (4/21), cortical or cerebral atrophy (4/21), nodular heterotopia (2/21) and reduced creatine levels in white matter (4/4). 4/21 adult patients went to mainstream school without the need of additional educational support and 1/21 lives independently. Early-onset patients had more severe involvement of visceral organs including liver, kidney and gut. All early-onset and half of late-onset patients presented with hyperammonaemia. Screened patients had normal ammonia at birth and received treatment preventing severe hyperammonaemia. ASL was sequenced (n = 19) and 20 mutations were found. Plasma argininosuccinate was higher in early-onset compared to late-onset patients. CONCLUSIONS: Our study further defines the natural history of argininosuccinic aciduria and genotype-phenotype correlations. The neurological phenotype does not correlate with the severity of hyperammonaemia and plasma argininosuccinic acid levels. The disturbance in nitric oxide synthesis may be a contributor to the neurological disease. Clinical trials providing nitric oxide to the brain merit consideration.
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Aciduria Argininosuccínica/patología , Aciduria Argininosuccínica/terapia , Adolescente , Adulto , Amoníaco/metabolismo , Ácido Argininosuccínico/sangre , Aciduria Argininosuccínica/sangre , Aciduria Argininosuccínica/genética , Niño , Preescolar , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Hiperamonemia/metabolismo , Hiperamonemia/patología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Mutación/genética , Fenotipo , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
AIMS: To estimate the effectiveness of pregnancy smoking cessation support delivered by short message service (SMS) text message and key parameters needed to plan a definitive trial. DESIGN: Multi-centre, parallel-group, single-blinded, individual randomized controlled trial. SETTING: Sixteen antenatal clinics in England. PARTICIPANTS: Four hundred and seven participants were randomized to the intervention (n = 203) or usual care (n = 204). Eligible women were < 25 weeks gestation, smoked at least one daily cigarette (> 5 pre-pregnancy), were able to receive and understand English SMS texts and were not already using text-based cessation support. INTERVENTION: All participants received a smoking cessation leaflet; intervention participants also received a 12-week programme of individually tailored, automated, interactive, self-help smoking cessation text messages (MiQuit). OUTCOME MEASUREMENTS: Seven smoking outcomes, including validated continuous abstinence from 4 weeks post-randomization until 36 weeks gestation, design parameters for a future trial and cost-per-quitter. FINDINGS: Using the validated, continuous abstinence outcome, 5.4% (11 of 203) of MiQuit participants were abstinent versus 2.0% (four of 204) of usual care participants [odds ratio (OR) = 2.7, 95% confidence interval (CI) = 0.93-9.35]. The Bayes factor for this outcome was 2.23. Completeness of follow-up at 36 weeks gestation was similar in both groups; provision of self-report smoking data was 64% (MiQuit) and 65% (usual care) and abstinence validation rates were 56% (MiQuit) and 61% (usual care). The incremental cost-per-quitter was £133.53 (95% CI = -£395.78 to 843.62). CONCLUSIONS: There was some evidence, although not conclusive, that a text-messaging programme may increase cessation rates in pregnant smokers when provided alongside routine NHS cessation care.
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Evaluación de Programas y Proyectos de Salud/métodos , Autocuidado/métodos , Cese del Hábito de Fumar/métodos , Envío de Mensajes de Texto , Adolescente , Adulto , Teorema de Bayes , Inglaterra , Femenino , Conductas Relacionadas con la Salud , Humanos , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Embarazo , Autocuidado/estadística & datos numéricos , Método Simple Ciego , Fumadores , Fumar/terapia , Cese del Hábito de Fumar/estadística & datos numéricos , Adulto JovenRESUMEN
Imaging is central to management of solid tumours in children. Conventional magnetic resonance imaging (MRI) is the standard imaging modality for tumours of the central nervous system (CNS) and limbs and is increasingly used in the abdomen. It provides excellent structural detail, but imparts limited information about tumour type, aggressiveness, metastatic potential or early treatment response. MRI based functional imaging techniques, such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, probe tissue properties to provide clinically important information about metabolites, structure and blood flow. This review describes the role of and evidence behind these functional imaging techniques in paediatric oncology and implications for integrating them into routine clinical practice.
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Imagen por Resonancia Magnética/métodos , Neoplasias/diagnóstico por imagen , Biomarcadores de Tumor/análisis , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Niño , Imagen de Difusión por Resonancia Magnética/métodos , Humanos , Espectroscopía de Resonancia MagnéticaRESUMEN
BACKGROUND: Smoking in pregnancy is a public health problem. Self-help smoking cessation support can help pregnant women to stop smoking, but the effects of delivering this kind of support via SMS text message are not known. A previous randomised controlled trial (RCT) demonstrated the feasibility and acceptability of providing such support to pregnant smokers using an automated, tailored text message intervention called MiQuit. This larger RCT will estimate key parameters for and will test the feasibility of delivering a major trial run within the United Kingdom National Health Service settings aimed at providing definitive evidence on the utility of MiQuit for helping pregnant smokers to stop. METHODS/DESIGN: This will be a multi-centre, parallel group RCT. Participants are being identified in 16 English antenatal care settings and must be >16 years old, pregnant, <25 weeks gestation, smoke >1 daily cigarette, have smoked >5 daily cigarettes before pregnancy, and able to understand texts in English. After consenting and the collection of baseline data, participants are randomised to control or intervention groups in a 1:1 ratio; randomisation is stratified by trial site and gestation and employs computer-generated pseudo-random code using random permuted blocks of randomly varying size, and held on a secure server. All participants receive a National Health Service (NHS) leaflet aimed at helping them to stop smoking. Intervention group women also receive the 12-week MiQuit programme of tailored, supportive, interactive text message, self-help cessation support. Women are followed up by telephone 4 weeks after randomisation and at 36 weeks gestation. The study aims to recruit 400 women, and with this sample we will be able to estimate trial centres' recruitment rates to within +/-1% (margin of error = half width of 95% confidence interval); individual trial groups' ascertainment of rates for smoking outcomes between 4 weeks after randomisation until approximately 36 weeks gestation to within +/-4%, and across both groups, the combined cessation rate at 36 weeks +/-3%. DISCUSSION: Pilot trial completion will provide data to facilitate planning for a definitive trial investigating whether MiQuit works for smoking cessation in pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02043509 Registered 14 January 2014.
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Protocolos Clínicos , Cese del Hábito de Fumar/métodos , Envío de Mensajes de Texto , Femenino , Humanos , Proyectos Piloto , Embarazo , Método Simple Ciego , Estadística como AsuntoRESUMEN
OBJECTIVE: To report a case of nonischemic dilated cardiomyopathy associated with autoimmune polyglandular syndrome (APS) type III. METHODS: A review of our patient's medical records was undertaken, and her clinical history, investigations, and outcome are described. In addition, a literature review of nonischemic dilated cardiomyopathy occurring in association with autoimmune polyendocrinopathies was performed. RESULTS: APS is diagnosed once a patient has developed at least 2 organ specific autoimmune diseases. APS III involves a combination of autoimmune diabetes and Graves' disease without adrenal insufficiency. Autoimmune cardiomyopathies are not described as a feature of this condition; however, there are a few reported cases of patients with autoimmune polyendocrinopathies developing a nonischemic dilated cardiomyopathy. In this case, a 30-year-old female developed vitiligo, Graves' disease, and latent autoimmune diabetes of the adult (LADA) over a 5-year period before presenting with conscious ventricular tachycardia (VT). This evolved into acute severe biventricular failure within a few weeks, which failed to resolve after adequate treatment of her other autoimmune conditions. CONCLUSION: Although nonischemic cardiomyopathies have been associated with APS in a few published cases, this is the first case to our knowledge in a patient with APS III.
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BACKGROUND: Cellulitis (erysipelas) is a recurring and debilitating bacterial infection of the skin and underlying tissue. We assessed the cost-effectiveness of prophylactic antibiotic treatment to prevent the recurrence of cellulitis using low dose penicillin V in patients following a first episode (6 months prophylaxis) and more recurrent cellulitis (12 months prophylaxis, or 6 months in those declining 12 months). METHODS: Within-trial cost-effectiveness analysis was conducted using the findings of two randomised placebo-controlled multicentre trials (PATCH I and PATCH II), in which patients recruited in the UK and Ireland were followed-up for up to 3 years. Incremental cost, reduction in recurrence, cost per recurrence prevented and cost/QALY were estimated. National unit and reference costs for England in 2010 were applied to resource use, exploring NHS and societal perspectives. A total of 397 patients from the two trials contributed to the analysis. RESULTS: There was a 29% reduction in the number of recurrences occurring within the trial (IRR: 0.71 95%CI: 0.53 to 0.90, pâ=â0.02), corresponding to an absolute reduction of recurrence of 0.31 recurrences/patient (95%CI: 0.05 to 0.59, pâ=â0.02). Incremental costs of prophylaxis suggested a small cost saving but were not statistically significant, comparing the two groups. If a decision-maker is willing to pay up to £25,000/QALY then there is a 66% probability of antibiotic prophylaxis being cost-effective from an NHS perspective, rising to 76% probability from a secondary, societal perspective. CONCLUSION: Following first episode or recurrent cellulitis of the leg, prophylactic low dose penicillin is a very low cost intervention which, on balance, is effective and cost-effective at preventing subsequent attacks. Antibiotic prophylaxis reduces cellulitis recurrence by nearly a third but is not associated with a significant increase in costs.
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Antibacterianos/economía , Antibacterianos/uso terapéutico , Profilaxis Antibiótica/economía , Celulitis (Flemón)/tratamiento farmacológico , Celulitis (Flemón)/prevención & control , Pierna/patología , Anciano , Antibacterianos/farmacología , Celulitis (Flemón)/economía , Análisis Costo-Beneficio , Costos y Análisis de Costo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Prevención Secundaria , Resultado del TratamientoRESUMEN
OBJECTIVES: Placental chorioangioma is a relatively rare condition that often results in serious prenatal complications and adverse pregnancy outcome. We report a case of a large chorioangioma that was prenatally diagnosed at 23 weeks with polyhydramnios and fetal anemia. With prenatal monitoring, transplacental therapy with a COX-2 inhibitor and intrauterine transfusion, the pregnancy resulted in the live birth at 30 weeks. Due to the paucity of evidence relating to the management protocols in cases of placental chorioangiomas, we have conducted a systematic review of the literature. METHODS: All reported cases in the English language were captured using the electronic databases. Bibliographies of relevant articles were manually searched. RESULTS: Sixty-four articles were included reporting 112 cases of placental chorioangioma. In 79, there was no prenatal treatment and in 33 there was in-utero treatment. A systematic comparison of antenatal complications and pregnancy outcomes was performed. No strong conclusion could be made due to the low number and quality of the reported cases. CONCLUSION: Placenta chorioangioma represents a challenge with its potentially serious complications adversely affecting pregnancy outcome. An international registry of pregnancies with this rare complication and documentation of pregnancy outcomes will improve the evidence base for prospective management.
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Hemangioma/diagnóstico , Enfermedades Placentarias/diagnóstico , Diagnóstico Prenatal , Adulto , Femenino , Terapias Fetales/métodos , Hemangioma/terapia , Humanos , Enfermedades Placentarias/terapia , Embarazo , Diagnóstico Prenatal/métodosRESUMEN
BACKGROUND: Cellulitis of the leg is a common bacterial infection of the skin and underlying tissue. We compared prophylactic low-dose penicillin with placebo for the prevention of recurrent cellulitis. METHODS: We conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only. RESULTS: A total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50). CONCLUSIONS: In patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research; PATCH I Controlled-Trials.com number, ISRCTN34716921.).
Asunto(s)
Antibacterianos/uso terapéutico , Celulitis (Flemón)/tratamiento farmacológico , Penicilinas/uso terapéutico , Anciano , Antibacterianos/efectos adversos , Celulitis (Flemón)/prevención & control , Método Doble Ciego , Femenino , Estudios de Seguimiento , Costos de la Atención en Salud , Servicios de Salud/economía , Servicios de Salud/estadística & datos numéricos , Humanos , Pierna , Masculino , Persona de Mediana Edad , Penicilinas/efectos adversos , Prevención SecundariaRESUMEN
OBJECTIVE: Changing trends in multiple sclerosis (MS) epidemiology may first be apparent in the childhood population affected with first onset acquired demyelinating syndromes (ADSs). We aimed to determine the incidence, clinical, investigative and magnetic resonance imaging (MRI) features of childhood central nervous system ADSs in the British Isles for the first time. METHODS: We conducted a population active surveillance study. All paediatricians, and ophthalmologists (n = 4095) were sent monthly reporting cards (September 2009-September 2010). International Paediatric MS Study Group 2007 definitions and McDonald 2010 MS imaging criteria were used for acute disseminated encephalomyelitis (ADEM), clinically isolated syndrome (CIS) and neuromyelitis optica (NMO). Clinicians completed a standard questionnaire and provided an MRI copy for review. RESULTS: Card return rates were 90%, with information available for 200/222 positive notifications (90%). After exclusion of cases, 125 remained (age range 1.3-15.9), with CIS in 66.4%, ADEM in 32.0% and NMO in 1.6%. The female-to-male ratio in children older than 10 years (n = 63) was 1.52:1 (p = 0.045). The incidence of first onset ADS in children aged 1-15 years old was 9.83 per million children per year (95% confidence interval [CI] 8.18-11.71). A trend towards higher incidence rates of ADS in children of South Asian and Black ethnicity was observed compared with White children. Importantly, a number of MRI characteristics distinguished ADEM from CIS cases. Of CIS cases with contrast imaging, 26% fulfilled McDonald 2010 MS diagnostic criteria. CONCLUSIONS: We report the highest surveillance incidence rates of childhood ADS. Paediatric MS diagnosis at first ADS presentation has implications for clinical practice and clinical trial design.