RESUMO
Sanfilippo syndrome results from inherited mutations in genes encoding lysosomal enzymes that catabolise heparan sulfate (HS), leading to early childhood-onset neurodegeneration. This study explores the therapeutic potential of photobiomodulation (PBM), which is neuroprotective and anti-inflammatory in several neurodegenerative diseases; it is also safe and PBM devices are readily available. We investigated the effects of 10-14 days transcranial PBM at 670 nm (2 or 4 J/cm2/day) or 904 nm (4 J/cm2/day) in young (3 weeks) and older (15 weeks) Sanfilippo or mucopolysaccharidosis type IIIA (MPS IIIA) mice. Although we found no PBM-induced changes in HS accumulation, astrocyte activation, CD206 (an anti-inflammatory marker) and BDNF expression in the brains of Sanfilippo mice, there was a near-normalisation of microglial activation in older MPS IIIA mice by 904 nm PBM, with decreased IBA1 expression and a return of their morphology towards a resting state. Immune cell immunophenotyping of peripheral blood with mass cytometry revealed increased pro-inflammatory signalling through pSTAT1 and p-p38 in NK and T cells in young but not older MPS IIIA mice (5 weeks of age), and expansion of NK, B and CD8+ T cells in older affected mice (17 weeks of age), highlighting the importance of innate and adaptive lymphocytes in Sanfilippo syndrome. Notably, 670 and 904 nm PBM both reversed the Sanfilippo-induced increase in pSTAT1 and p-p38 expression in multiple leukocyte populations in young mice, while 904 nm reversed the increase in NK cells in older mice. In conclusion, this is the first study to demonstrate the beneficial effects of PBM in Sanfilippo mice. The distinct reduction in microglial activation and NK cell pro-inflammatory signalling and number suggests PBM may alleviate neuroinflammation and lymphocyte activation, encouraging further investigation of PBM as a standalone, or complementary therapy in Sanfilippo syndrome.
Assuntos
Encéfalo , Células Matadoras Naturais , Terapia com Luz de Baixa Intensidade , Microglia , Mucopolissacaridose III , Animais , Microglia/efeitos da radiação , Microglia/metabolismo , Camundongos , Mucopolissacaridose III/radioterapia , Mucopolissacaridose III/patologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos da radiação , Células Matadoras Naturais/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Raios Infravermelhos/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , FemininoRESUMO
INTRODUCTION: Two-week wait (TWW) volume and colorectal cancer (CRC) detection pose an increasing challenge for NHS cancer services. Primary aims were to assess the introduction of faecal immunochemical tests (FIT) into clinical practice at our centre, the impact on TWW referral volume and CRC diagnoses, and to provide an update to previously published work. A secondary aim was to correlate FIT value and investigation. METHODS: TWW CRC data following incorporation of FIT into clinical practice were analysed (1 June 2019-31 July 2021). Parameters assessed were monthly referral volume, CRC detection, primary care FIT volume and secondary care investigations. Referrals and CRC detection rates were compared with previously published data (2009-2019). Data relating to primary care FIT were collated from Berkshire and Surrey Pathology Services. RESULTS: TWW referrals increased 360% (2009-2020). CRC incidence decreased from 8.87% to 3.24%. Following incorporation into clinical practice, primary care FIT requests have increased to >450/month and accompanied 1,722/4,796 referrals. CRC incidence is static (3-4%). Patients with FIT <10µg Hb/g faeces undergo radiological imaging more commonly, whereas FIT-positive patients are more likely to undergo endoscopy, although the difference is not statistically significant. CONCLUSIONS: No significant change in CRC diagnosis was observed, despite increasing TWW referrals. Increasing utilisation of FIT in both primary and secondary care has helped maintain CRC detection while avoiding diagnostic delay. This study supports growing evidence highlighting the value of FIT in triage, referral and TWW investigation. FIT appears increasingly important for allocating secondary care resources (endoscopy), while guiding primary care referral. Additional low-cost strategies to determine prioritisation or reassurance (e.g. repeat FIT) require further evaluation.
Assuntos
Neoplasias Colorretais , Humanos , Sensibilidade e Especificidade , Neoplasias Colorretais/patologia , Diagnóstico Tardio , Colonoscopia , Fezes/química , Detecção Precoce de Câncer/métodos , Hemoglobinas/análiseRESUMO
INTRODUCTION: A wandering spleen occurs when laxity or absence of the suspensory ligaments allows migration throughout the abdomen. Gastric outlet obstruction resulting from this abnormality is rare. We present a systematic literature search and a case that was managed successfully with surgical intervention at our centre. METHODS: A systematic search of the PubMed, Embase™, Medline® and Google Scholar™ databases was carried out employing the combined search terms "gastric outlet obstruction" AND "wandering spleen". Six results were included for final analysis. RESULTS: All six search results described a single case each. Patients underwent surgical management (open or laparoscopic) after initial investigation utilising a range of modalities. There were no mortalities reported at 90 days. The single case we present was complicated by gastric perforation; the patient made a successful recovery following open splenopexy and stapled wedge resection of the stomach. CONCLUSIONS: A wandering spleen is a rare diagnosis and there are only six reported cases of gastric outlet obstruction secondary to a wandering spleen in the literature. None report associated gastric perforation. There are a variety of presenting symptoms, intraoperative findings and operative techniques used to address the gastrosplenic abnormality. The case reported by our centre adds to this limited evidence base and demonstrates a successful outcome from definitive surgical management. We highlight the need to seek early gastro-oesophageal expertise if any gastric pathology is found together with anatomical abnormality of the spleen.
Assuntos
Obstrução da Saída Gástrica , Laparoscopia , Baço Flutuante , Humanos , Obstrução da Saída Gástrica/etiologia , Obstrução da Saída Gástrica/cirurgia , Laparoscopia/métodos , Esplenectomia/métodos , Baço Flutuante/complicações , Baço Flutuante/diagnóstico por imagem , Baço Flutuante/cirurgia , Relatos de Casos como AssuntoRESUMO
Alloimmunization to red blood cell (RBC) antigens post-allogeneic stem cell transplantation (allo-SCT) appears to be quite rare. The D antigen (RhD) is considered the most immunogenic RBC antigen with possibly a third of RhD-negative individuals exposed to RhD-positive RBC transfusions becoming alloimmunized. Though variable, most are detectable within a year of exposure, and the median time between exposure and detection is estimated to be about a month. We report the detection of anti-D in an allogeneic bone marrow transplant (allo-BMT) recipient about five years following last exposure to RhD-positive RBC.
Assuntos
Anemia Hemolítica Autoimune , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Medula Óssea , Transfusão de Eritrócitos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , HumanosRESUMO
AIM: Postoperative anastomotic leakage (AL) or bleeding (AB) significantly impacts on patient outcome following colorectal resection. To minimize such complications, surgeons can utilize different techniques perioperatively to assess anastomotic integrity. We aim to assess published anastomotic complication rates following left-sided colonic resection, comparing the use of intra-operative flexible endoscopy (FE) against conventional tests used to assess anastomotic integrity. METHODS: PubMed/MEDLINE and Embase online databases were searched for non-randomized and randomized case-control studies that investigated postoperative AL and/or AB rates in left-sided colonic resections, comparing intra-operative FE against conventional tests. Data from eligible studies were pooled, and a meta-analysis using Review Manager 5.3 software was performed to assess for differences in AL and AB rates. RESULTS: Data from six studies were analysed to assess the impact of FE on postoperative AL and AB rates (1084 and 751 patients respectively). Use of FE was associated with reduced postoperative AL and AB rates, from 6.9% to 3.5% and 5.8% to 2.4% respectively. Odds ratios favoured intra-operative FE: 0.37 (95% CI 0.21-0.68, P = 0.001) for AL and 0.35 (95% CI 0.15-0.82, P = 0.02) for AB. CONCLUSION: This meta-analysis showed that the use of intra-operative FE is associated with a reduced rate of postoperative AL and AB, compared to conventional anastomotic testing methods.
Assuntos
Colectomia/métodos , Colonoscopia/instrumentação , Colostomia/efeitos adversos , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Estudos de Casos e Controles , Colo/cirurgia , Colonoscopia/métodos , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Reto/cirurgiaRESUMO
BACKGROUND: Recently published clinical trials have resulted in a significant change in the guidelines used to manage patients suffering an acute ischaemic stroke. New neuro-interventional techniques have revolutionised stroke outcomes. Currently, such services are only available in two specialist centres. AIMS: We attempted to evaluate the need for the provision of routine computed tomography (CT) angiography and neuro-interventional services at a university teaching hospital in Limerick. METHODS: A retrospective study was performed based on data collated by the stroke service, University Hospital Limerick (UHL). All patients with a suspected acute ischaemic stroke of anterior circulation and known evolution were included. Baseline clinical and imaging characteristics, thrombolysis data, stroke unit admission rates and discharge destinations were recorded. RESULTS: All 141 patients were suitable for CT angiography and should be performed in accordance with guidelines. Additionally, 165 patients excluded from the study due to an unknown stroke evolution timeframe may have benefitted. Non-contrast CT scan confirmed just 12 anterior circulation strokes. The need for neuro-interventional services proved more difficult to assess, primarily due to the lack of provision of routine CT angiography, employed to confirm anterior circulation occlusion. Secondary results showed a thrombolysis rate of 10.8% and confirmed that time efficiencies result in higher thrombolysis eligibility rates. Stroke unit admissions and discharge destinations were also recorded. CONCLUSION: UHL should provide routine CT angiography to all patients presenting with acute ischaemic stroke in line with current guidelines. The need for provision of neuro-interventional services on-site proved more difficult to assess and requires further analysis.
Assuntos
Angiografia/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. MATERIALS AND METHODS: Ruptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155µm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5µm) and multi-detector CT resolution (744µm) was also made. RESULTS: Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200µm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155µm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155µm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. CONCLUSION: The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk.
Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Dissecção Aórtica/diagnóstico por imagem , Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , RiscoRESUMO
Dormia baskets are commonly used during endoscopic retrograde cholangiopancreatography (ERCP). One complication is basket retention, through impaction with a gallstone or wire fracture. We describe a case where the external handle of the basket snapped causing retained basket plus large gallstone impacted in the common bile duct (CBD). Following laparoscopic cholecystectomy, laparoscopic CBD exploration allowed direct stone fragmentation under vision with the choledochoscope. Fragments were removed using a choledochoscopic basket and Fogarty catheter, and the basket was withdrawn. Literature search identified 114 cases of retained baskets with management including shockwave lithotripsy (27%), papillary balloon dilatation (22%), open CBD exploration (11%), and one laparoscopic case.
RESUMO
OBJECTIVE/BACKGROUND: Carotid artery stenting (CAS) in calcified arteries carries a higher peri-operative risk. This study investigates the relationship between the stretching limits of carotid plaque samples and calcification in order to determine a stretch tolerance criterion for endovascular intervention. METHODS: Seventeen carotid plaque samples were acquired from standard endarterectomy procedures. The maximum stretch capability of the global plaque was determined by circumferentially extending the tissue to complete failure. Quantitative assessment of calcification was performed using high resolution computed tomography, including measures of percent calcification volume fraction (%CVF) and calcification configuration. Maximum stretch properties were then related to calcification measures in order to evaluate the predictive power of calcification for determining plaque stretching limits. RESULTS: A strong negative correlation was found between %CVF and stretch ratio with respect to specific calcification configuration types. All plaques with < 70% stenosis superseded the minimum required stretch threshold. Severe stenosis (> 70%) warrants a stretch of at least 2.33 during revascularisation and only plaques containing concentric calcifications with < 20% CVF successfully reached this minimum required stretch threshold. CONCLUSION: The addition of calcification measures to the stenosis classification may help in guiding endovascular intervention techniques to achieve a balance between an acceptable residual patency level while avoiding plaque rupture in calcified carotid plaques.
Assuntos
Calcinose/patologia , Estenose das Carótidas/patologia , Estenose das Carótidas/cirurgia , Elasticidade , Placa Aterosclerótica/patologia , Placa Aterosclerótica/cirurgia , Idoso , Angioplastia/efeitos adversos , Calcinose/complicações , Calcinose/cirurgia , Endarterectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Stents/efeitos adversos , Técnicas de Cultura de TecidosRESUMO
BACKGROUND: The UK Supreme Court recently ruled that when consenting patients for treatments or procedures, clinicians must also discuss any associated material risks. We surveyed medical staff at a large UK teaching hospital in order to ascertain knowledge of consent law and current understanding of this change. MATERIALS AND METHODS: Email survey sent to medical staff in all specialities at Norfolk and Norwich University Hospital in February 2016. RESULTS: 245 responses (141 Consultants and 104 junior doctors, response rate 32%). 82% consent patients for procedures at least monthly and 23% daily. 31% were not familiar with the concept of material risk. 35% were familiar with the recent change in consent law, 41% were not. 18% were "very uncertain" and 64% "a little uncertain" that their consenting process meets current legal requirements. >92% think that landmark cases and changes in law should be discussed through professional bodies and circulated better locally. CONCLUSION: The majority were not familiar with the concept of material risk and recent legal changes. A majority were not confident that their practice meets current requirements, suggesting that recent changes in consent law may not be widely understood at this hospital. We suggest more guidance and education may be necessary than is currently available. Increased understanding of recent changes to consent law will reduce the risk taken by NHS trusts and offer patients a service compliant with Supreme Court guidance.
RESUMO
BACKGROUND AND AIMS: High-density lipoprotein (HDL) cholesterol efflux capacity in adults may be a measure of the atheroprotective property of HDL. Little however, is known about HDL cholesterol efflux capacity in childhood. We aimed to investigate the relationship between HDL cholesterol efflux capacity and childhood anthropometrics in a longitudinal study. METHODS AND RESULTS: Seventy-five children (mean age = 9.4 ± 0.4 years) were followed from birth until the age of 9 years. HDL cholesterol efflux capacity was determined at age 9 by incubating serum-derived HDL-supernatants with 3H-cholesterol labeled J774 macrophages and percentage efflux determined. Mothers provided dietary information by completing food frequency questionnaires in early pregnancy and then 5 years later on behalf of themselves and their children. Pearson's correlations and multiple regression analyses were conducted to confirm independent associations with HDL efflux. There was a negative correlation between HDL cholesterol efflux capacity and waist circumference at age 5 (r = -0.3, p = 0.01) and age 9 (r = -0.24, p = 0.04) and BMI at age 5 (r = -0.45, p = 0.01) and age 9 (r = -0.19, p = 0.1). Multiple regression analysis showed that BMI at age 5 remained significantly associated with reduced HDL cholesterol efflux capacity (r = -0.45, p < 0.001). HDL-C was negatively correlated with energy-adjusted fat intake (r = -0.24, p = 0.04) and positively correlated with energy-adjusted protein (r = 0.24, p = 0.04) and starch (r = 0.29, p = 0.01) intakes during pregnancy. HDL-C was not significantly correlated with children dietary intake at age 5. There were no significant correlations between maternal or children dietary intake and HDL cholesterol efflux capacity. CONCLUSIONS: This novel analysis shows that efflux capacity is negatively associated with adiposity in early childhood independent of HDL-C.
Assuntos
Adiposidade , Fenômenos Fisiológicos da Nutrição Infantil , HDL-Colesterol/sangue , Dieta , Macrófagos/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Biomarcadores/sangue , Índice de Massa Corporal , Linhagem Celular , Criança , Pré-Escolar , Dieta/efeitos adversos , Registros de Dieta , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Exposição Materna/efeitos adversos , Avaliação Nutricional , Gravidez , Análise de Regressão , Inquéritos e Questionários , Fatores de TempoRESUMO
This study assesses the relationship between body mass index (BMI) and adult chronic diseases (diabetes mellitus type 2 [DM2], cardiovascular diseases [CVD] and cancers), in grandparents in the Lifeways Cross-Generation Cohort Study. BMI was either measured or reported, at baseline or 10-year follow-up, in 1,244 grandparents. Cumulative morbidity data were recorded at baseline, 3 and 10-year follow-up through questionnaires, General Practice note search, or both. Just over 42% of grandparents were overweight and 32.1% obese. In the multivariate analysis BMI showed a strong linear association with both DM2 (ptrend <0.001) and CVD (ptrend <0.001). There were no significant associations with cancers, but case numbers were small. Results were similar for waist circumference. This prospective study presents novel Irish data and confirms other recent Irish cross-sectional reports on adiposity and adult chronic disease, highlighting the need for effective health promotion interventions in older adults.
RESUMO
OBJECTIVE: To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid-trimester sonographic cervical length (CL) ≤ 25 mm. METHODS: This was an updated systematic review and meta-analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid-trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. RESULTS: Five trials involving 974 women were included. A meta-analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52-0.83); P = 0.0005; five studies; 974 women). Meta-analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at < 28 to < 36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95% CI, 0.27-0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95% CI, 0.38-0.91)), birth weight < 1500 g (RR, 0.52 (95% CI, 0.34-0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95% CI, 0.50-0.91)). There were no significant differences in neurodevelopmental outcomes at 2 years of age between the vaginal progesterone and placebo groups. CONCLUSION: This updated systematic review and meta-analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid-trimester CL ≤ 25 mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18-24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤ 25 mm. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Assuntos
Colo do Útero/efeitos dos fármacos , Nascimento Prematuro/prevenção & controle , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Administração Intravaginal , Medida do Comprimento Cervical , Colo do Útero/patologia , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado do TratamentoRESUMO
A 58-year-old woman was referred to our cardiology service with chest pain, exertional dyspnoea and palpitations on a background of known Fabry disease diagnosed with genetic testing in 1994. ECG showed sinus rhythm, shortened PR interval, widespread t wave inversion, q waves in the lateral leads and left ventricular hypertrophy (LVH). Coronary angiogram showed only mild atheroma. Transthoracic echocardiogram showed anterolateral LVH and reduced left ventricular cavity size in keeping with Fabry cardiomyopathy. Cardiac MRI demonstrated asymmetric hypertrophy with evidence of diffuse myocardial fibrosis in the maximally hypertrophied segments from base to apex with late gadolinium enhancement in the anterior and anteroseptal walls. This was quite an atypical appearance for Fabry cardiomyopathy. This case highlights the heterogeneity of patterns of cardiac involvement that may be associated with this rare X-linked lysosomal disorder.
Assuntos
Doença de Fabry/complicações , Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/etiologia , Dor no Peito/etiologia , Angiografia Coronária , Diagnóstico Diferencial , Dispneia/etiologia , Ecocardiografia , Eletrocardiografia , Doença de Fabry/genética , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
We compared the cost-effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality-adjusted-life-years (QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four decision-making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost-effectiveness ratio (ICER) of £28,137 per additional QALY gained for HBeAg-negative patients. For HBeAg-positive patients, using Fibroscan was the most cost-effective option with an ICER of £23,345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥ F2 prevalence and the benefit of treatment in patients with F0-F1. For HBeAg-negative patients, strategies excluding NITs were the most cost-effective: treating all patients regardless of fibrosis level if the high cost-effectiveness threshold of £30,000 is accepted; watchful waiting if not. For HBeAg-positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost-effective option.
Assuntos
Análise Custo-Benefício , Testes Diagnósticos de Rotina/economia , Custos de Cuidados de Saúde , Cirrose Hepática/diagnóstico , Cirrose Hepática/economia , Antivirais/uso terapêutico , Erros de Diagnóstico/economia , Erros de Diagnóstico/estatística & dados numéricos , Antígenos E da Hepatite B/sangue , Hepatite B Crônica , Humanos , Cirrose Hepática/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida , Reino Unido , Carga ViralRESUMO
Eight captive female Magellanic penguins (Spheniscus magellanicus) were monitored over a 10week period, commencing at 5weeks prior to egg lay (EL), to increase our understanding of the species' reproductive biology. Females in cordoned nest sites underwent cloacal artificial insemination (AI) every 4-7days with different semen donors for each insemination. The EL interval was 97.9±3.6h (range: 84-108h) and paternity analyses revealed that conceptive inseminations occurred from 11.5 to 4.5days before oviposition. A biphasic pattern of estradiol, testosterone, progesterone and the biochemical analytes triglyceride, iron, calcium and phosphorus occurred in relation to EL, with values increasing (P<0.05) to maximal concentrations during the three weeks preceding oviposition, then decreasing (P<0.05) rapidly after oviposition completion. In comparison with post-lay (baseline) values, concentrations of estradiol and testosterone relative to the first oviposition were elevated at Week-5, and those of triglyceride, a yolk formation index, as well as iron, calcium and phosphorus, became elevated at Week-4 (P<0.05). Collective data indicate an estimated total egg formation interval of 29days, with oviducal transit of the ovulated ovum occurring over the majority of the â¼4day EL interval. These findings indicate that egg formation is prolonged with folliculogenesis initiated at 5weeks or more prior to oviposition. Consequently, the period of folliculogenesis and egg formation is estimated to overlap with the final â¼3weeks that wild females spend at sea prior to returning to land for breeding.