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1.
Clin Radiol ; 79(5): 371-377, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38341344

RESUMO

AIM: To evaluate and compare the rates of local recurrence in hepatocellular carcinoma (HCC) patients who undergo selective transarterial radioembolisation (TARE) or transarterial chemoembolisation (TACE) and achieve a complete response (CR) radiologically. MATERIALS AND METHODS: All patients undergoing treatment with TARE or TACE at a single academic institution were reviewed retrospectively. Those who had been treated previously, presented with multifocal disease, had non-selective TARE or TACE, or did not achieve a complete response (CR) radiologically were excluded. RESULTS: In total 110 patients were included (TACE n=60 [54.5%]; TARE n=50 [45.5%]). TARE patients were older (66.4 ± 9.4 versus 61.2 ± 5.6 years, p<0.001) and had larger tumours (4.4 ± 2.2 versus 3 ± 1.4 cm, p=0.002). TACE patients were significantly more likely to suffer a local recurrence (31/60, 51.7% versus 9/50, 18%, p<0.001) and had a significantly shorter time to recurrence (median 8.3 {interquartile range [IQR]}: 12 versus median 17.9 [IQR: 23.5] months, p=0.001). A local time to progression (TTP) Kaplan-Meier curve demonstrated TACE patients had a significantly shorter local TTP (hazard ratio [HR]: 7.2; 95% confidence interval [CI]: 3.64-14.24; p<0.001) and treatment modality (TACE or TARE; HR: 0.05; 95% CI: 0.005-0.5; p=0.01) was found to be associated with local recurrences on multivariate Cox proportional HR analysis. When overall TTP was evaluated, again TACE patients were found to have a significantly shorter TTP (HR: 2.13 [1.28-3.53], p=0.004). CONCLUSION: In HCC patients undergoing selective treatment who achieve a CR radiologically, those treated with TARE may be less likely to suffer recurrence, either local or general, than those treated with TACE.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/etiologia , Estudos Retrospectivos , Quimioembolização Terapêutica/efeitos adversos , Modelos de Riscos Proporcionais , Resposta Patológica Completa , Resultado do Tratamento
2.
J Appl Physiol (1985) ; 132(1): 187-198, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34855522

RESUMO

Simulated military operational stress (SMOS) provides a useful model to better understand resilience in humans as the stress associated with caloric restriction, sleep deficits, and fatiguing exertion degrades physical and cognitive performance. Habitual physical activity may confer resilience against these stressors by promoting favorable use-dependent neuroplasticity, but it is unclear how physical activity, resilience, and corticospinal excitability (CSE) relate during SMOS. To examine associations between corticospinal excitability, physical activity, and physical performance during SMOS. Fifty-three service members (age: 26 ± 5 yr, 13 women) completed a 5-day and -night intervention composed of familiarization, baseline, SMOS (2 nights/days), and recovery days. During SMOS, participants performed rigorous physical and cognitive activities while receiving half of normal sleep (two 2-h blocks) and caloric requirements. Lower and upper limb CSE were determined with transcranial magnetic stimulation (TMS) stimulus-response curves. Self-reported resilience, physical activity, military-specific physical performance (TMT), and endocrine factors were compared in individuals with high (HIGH) and low CSE based on a median split of lower limb CSE at baseline. HIGH had greater physical activity and better TMT performance throughout SMOS. Both groups maintained physical performance despite substantial psychophysiological stress. Physical activity, resilience, and TMT performance were directly associated with lower limb CSE. Individual differences in physical activity coincide with lower (but not upper) limb CSE. Such use-dependent corticospinal excitability directly relates to resilience and physical performance during SMOS. Future studies may use noninvasive neuromodulation to clarify the interplay among CSE, physical activity, and resilience and improve physical and cognitive performance.NEW & NOTEWORTHY We demonstrate that individual differences in physical activity levels coincide with lower limb corticospinal excitability. Such use-dependent corticospinal excitability directly relates to resilience and physical performance during a 5-day simulation of military operational stress with caloric restriction, sleep restriction and disruption, and heavy physical and cognitive exertion.


Assuntos
Militares , Córtex Motor , Adulto , Potencial Evocado Motor , Feminino , Humanos , Desempenho Físico Funcional , Tratos Piramidais , Estimulação Magnética Transcraniana , Adulto Jovem
3.
Brain Res ; 1761: 147395, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33662340

RESUMO

Transcranial magnetic stimulation (TMS) is increasingly used to examine lower extremity corticospinal excitability (CSE) in clinical and sports research. Because CSE is task-specific, there is growing emphasis on the use of ecological tasks. Nevertheless, the comparative reliability of CSE measurements during established (e.g. knee extensions; KE) and more recent ecological (e.g. squats; SQT) lower extremity tasks has received less attention. The aim of this study was to compare the test-retest reliability of CSE, force, and muscle activity (EMG) during isometric SQT and KE. 19 right-footed men (age: 25 ± 5 yrs) with similar fitness and body composition performed SQT (N = 7) or KE (N = 12) on two consecutive days. Force and EMG were recorded during maximum voluntary isometric contractions (MVC). Corticospinal excitability was determined in the dominant leg during light (15% MVC) contractions based on motor evoked potential (MEP) stimulus-response-curves (SRC). Test-retest reliability, absolute agreement, and consistency were determined for force, EMG, and SRC MEP maximum (MEPMAX) and rising phase midpoint (V50). As a secondary analysis, all outcomes were compared between groups with mixed-methods ANCOVAs (Task × Time, covariate: body-fat-percentage). Compared with SQT, KE displayed better test-retest reliability and agreement for MEPMAX whereas V50, force, and EMG were similarly reliable. Force (p = 0.01) and MEPMAX (p = 0.02) were also greater during KE despite a similar V50 (p = 0.11). Differences in test-retest reliability, absolute agreement, and between-group comparisons highlight the need to carefully select lower limb TMS assessment tasks and encourage future efforts to balance ecological validity with statistical sensitivity.

4.
Exp Brain Res ; 239(4): 1099-1110, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33547521

RESUMO

INTRODUCTION: The double-cone coil (D-CONE) is frequently used in transcranial magnetic stimulation (TMS) experiments that target the motor cortex (M1) lower-limb representation. Anecdotal evidence and modeling studies have shed light on the off-target effects of D-CONE TMS but the physiological extent remains undetermined. PURPOSE: To characterize the off-target effects of D-CONE TMS based on bilateral corticospinal responses in the legs and hands. METHODS: Thirty (N = 30) participants (9 women, age: 26 ± 5yrs) completed a stimulus-response curve procedure with D-CONE TMS applied to the dominant vastus lateralis (cVL) and motor-evoked potentials (MEPs) recorded in each active VL and resting first dorsal interosseous (FDI). As a positive control (CON), the dominant FDI was directly targeted with a figure-of-eight coil and MEPs were similarly recorded in each active FDI and resting VL. MEPMAX, V50 and MEP latencies were compared with repeated-measures ANOVAs or mixed-effects analysis and Bonferroni-corrected pairwise comparisons. RESULTS: Off-target responses were evident in all muscles, with similar MEPMAX in the target (cVL) and off-target (iVL) leg (p = 0.99) and cFDI compared with CON (p = 0.99). cFDI and CON MEPMAX were greater than iFDI (p < 0.01). A main effect of target (p < 0.001) indicated that latencies were shorter with CON but similar in all muscles with D-CONE. DISCUSSION: Concurrent MEP recordings in bilateral upper- and lower-extremity muscles confirm that lower-limb D-CONE TMS produces substantial distance-dependent off-target effects. In addition to monitoring corticospinal responses in off-target muscles to improve targeting accuracy in real-time, future studies may incorporate off-target information into statistical models post-hoc.


Assuntos
Córtex Motor , Estimulação Magnética Transcraniana , Pré-Escolar , Potencial Evocado Motor , Feminino , Mãos , Humanos , Extremidade Inferior , Músculo Esquelético
6.
AJNR Am J Neuroradiol ; 40(9): 1438-1444, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31371359

RESUMO

BACKGROUND AND PURPOSE: Working memory impairment is one of the most troubling and persistent symptoms after mild traumatic brain injury (MTBI). Here we investigate how working memory deficits relate to detectable WM microstructural injuries to discover robust biomarkers that allow early identification of patients with MTBI at the highest risk of working memory impairment. MATERIALS AND METHODS: Multi-shell diffusion MR imaging was performed on a 3T scanner with 5 b-values. Diffusion metrics of fractional anisotropy, diffusivity and kurtosis (mean, radial, axial), and WM tract integrity were calculated. Auditory-verbal working memory was assessed using the Wechsler Adult Intelligence Scale, 4th ed, subtests: 1) Digit Span including Forward, Backward, and Sequencing; and 2) Letter-Number Sequencing. We studied 19 patients with MTBI within 4 weeks of injury and 20 healthy controls. Tract-Based Spatial Statistics and ROI analyses were performed to reveal possible correlations between diffusion metrics and working memory performance, with age and sex as covariates. RESULTS: ROI analysis found a significant positive correlation between axial kurtosis and Digit Span Backward in MTBI (Pearson r = 0.69, corrected P = .04), mainly present in the right superior longitudinal fasciculus, which was not observed in healthy controls. Patients with MTBI also appeared to lose the normal associations typically seen in fractional anisotropy and axonal water fraction with Letter-Number Sequencing. Tract-Based Spatial Statistics results also support our findings. CONCLUSIONS: Differences between patients with MTBI and healthy controls with regard to the relationship between microstructure measures and working memory performance may relate to known axonal perturbations occurring after injury.


Assuntos
Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/psicologia , Encéfalo/diagnóstico por imagem , Memória de Curto Prazo , Adolescente , Adulto , Idoso , Axônios/metabolismo , Biomarcadores , Água Corporal/metabolismo , Imagem de Difusão por Ressonância Magnética , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Testes Neuropsicológicos , Estudos Prospectivos , Escalas de Wechsler , Substância Branca/diagnóstico por imagem , Adulto Jovem
7.
J Eur Acad Dermatol Venereol ; 33(7): 1325-1330, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30977217

RESUMO

BACKGROUND: Patients with psoriasis are at risk of a co-morbid diagnosis of depression and/or anxiety. It is therefore essential for dermatologists to have valid and effective instruments that can screen and monitor depression and anxiety symptoms in psoriasis patients. OBJECTIVE: The aim of this study was to validate the Mental Health Inventory (MHI-5) as a brief measure that can be used to evaluate psychological distress related to anxiety and depression in psoriasis patients. METHODS: The sample included 76 adult dermatological outpatients diagnosed with psoriasis. Participants completed the MHI-5, the Hospital Anxiety and Depression Scale (HADS) and six subscales of the Self-Compassion Scale (SCS). Confirmatory factor analysis (CFA) was applied to examine the factor structure of MHI-5. Convergent validity was examined by applying correlations among all measures. Discriminant validity was examined by applying hierarchical regression models. Reliability was examined by calculating Cronbach's alpha coefficient. RESULTS: Confirmatory factor analysis showed that the proposed one-factor model has a good fit to the data. The MHI-5 demonstrated satisfactory convergent validity by yielding significant moderate to strong correlations with the HADS and with the positive and negative subscales of the SCS. Discriminant validity was also evident with being at risk of anxiety predicting MHI-5 scores above and beyond the effect of gender and age. Hierarchical regressions were not performed because a very small number of participants (n = 3) were classified at risk of depression. The MHI-5 showed high internal consistency (α = 0.84). CONCLUSION: This investigation provided evidence that MHI-5 is a reliable and valid instrument that can be used to effectively capture psychological distress in psoriasis patients.


Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Psoríase/psicologia , Angústia Psicológica , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Ansiedade/etiologia , Depressão/etiologia , Análise Fatorial , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
8.
Diagn Interv Imaging ; 100(1): 39-46, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30082184

RESUMO

PURPOSE: The goal of this retrospective review was to determine the clinical relevance of one-month post-treatment imaging in the selective internal radiation therapy (SIRT) patient population by reporting the incidence of change in clinical management. MATERIALS AND METHODS: Between January 2012 and January 2016, 85 patients underwent 109 SIRT treatments for either primary or secondary hepatic malignancies. There were 59 men and 26 women with a mean age of 62.4 years (range: 39-89 years). Patients' medical records were retrospectively reviewed for procedural, historical, laboratory and imaging information. The imaging study was considered to have changed patients' clinical management if it resulted in the addition of a new procedure, canceling of a planned procedure or change in systemic therapy. RESULTS: The one-month post-treatment imaging findings led to management changes in 10 of 109 (9.2%) of treatments. When evaluated by cancer type, 2/61 (3.3%) hepatocellular carcinoma (HCC) treatments had management changed while 8/48 (16.7%) non-HCC treatments underwent management change (P=0.03). This difference was also significant at multivariate analysis (P=0.03; odds ratio: 0.17 [0.03-082]). CONCLUSION: Management is rarely changed by one-month post-SIRT imaging in patients with HCC and thus is likely unwarranted. Conversely, in non-HCC patients, one month post-SIRT imaging led to a significant percentage of clinical management changes suggesting that one month imaging in this setting is likely warranted.


Assuntos
Tomada de Decisão Clínica , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Feminino , Humanos , Masculino , Microesferas , Pessoa de Meia-Idade , Estudos Retrospectivos , Radioisótopos de Ítrio
9.
AJNR Am J Neuroradiol ; 39(12): 2200-2204, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30498019

RESUMO

BACKGROUND AND PURPOSE: Mild traumatic brain injury is a leading cause of death and disability worldwide with 42 million cases reported annually, increasing the need to understand the underlying pathophysiology because this could help guide the development of targeted therapy. White matter, particularly the corpus callosum, is susceptible to injury. Animal models suggest stretch-induced mechanoporation of the axonal membrane resulting in ionic shifts and altered sodium ion distribution. The purpose of this study was to compare the distribution of total sodium concentration in the corpus callosum between patients with mild traumatic brain injury and controls using sodium (23Na) MR imaging. MATERIALS AND METHODS: Eleven patients with a history of mild traumatic brain injury and 10 age- and sex-matched controls underwent sodium (23Na) MR imaging using a 3T scanner. Total sodium concentration was measured in the genu, body, and splenium of the corpus callosum with 5-mm ROIs; total sodium concentration of the genu-to-splenium ratio was calculated and compared between patients and controls. RESULTS: Higher total sodium concentration in the genu (49.28 versus 43.29 mmol/L, P = .01) and lower total sodium concentration in the splenium (which was not statistically significant; 38.35 versus 44.06 mmol/L, P = .08) was seen in patients with mild traumatic brain injury compared with controls. The ratio of genu total sodium concentration to splenium total sodium concentration was also higher in patients with mild traumatic brain injury (1.3 versus 1.01, P = .001). CONCLUSIONS: Complex differences are seen in callosal total sodium concentration in symptomatic patients with mild traumatic brain injury, supporting the notion of ionic dysfunction in the pathogenesis of mild traumatic brain injury. The total sodium concentration appears to be altered beyond the immediate postinjury phase, and further work is needed to understand the relationship to persistent symptoms and outcome.


Assuntos
Concussão Encefálica/metabolismo , Corpo Caloso/química , Sódio/análise , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
10.
J Diabetes Res ; 2018: 3061620, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30599002

RESUMO

Precision medicine, the concept that specific treatments can be targeted to groups of individuals with specific genetic, cellular, or molecular features, is a key aspect of modern healthcare, and its use is rapidly expanding. In diabetes, the application of precision medicine has been demonstrated in monogenic disease, where sulphonylureas are used to treat patients with neonatal diabetes due to mutations in ATP-dependent potassium (KATP) channel genes. However, diabetes is highly heterogeneous, both between and within polygenic and monogenic subtypes. Making the correct diagnosis and using the correct treatment from diagnosis can be challenging for clinicians, but it is crucial to prevent long-term morbidity and mortality. To facilitate precision medicine in diabetes, research is needed to develop a better understanding of disease heterogeneity and its impact on potential treatments for specific subtypes. Animal models have been used in diabetes research, but they are not translatable to humans in the majority of cases. Advances in molecular genetics and functional laboratory techniques and availability and sharing of large population data provide exciting opportunities for human studies. This review will map the key elements of future diabetes research in humans and its potential for clinical translation to promote precision medicine in all diabetes subtypes.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Medicina de Precisão , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Humanos
11.
Diagn Interv Imaging ; 99(2): 99-104, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28844611

RESUMO

PURPOSE: To evaluate the effect of catheter connections on drainage catheters' flow rate. MATERIALS AND METHOD: The in vitro model used commercially available catheters (8.5-F, 10.2-F, 12-F, and 14-F), connections - Luer-lok (2.33mm inner diameter), and stopcocks (1.33mm, 2.00mm, and 2.67mm inner diameters), water, ultrasound gel, textured vegetable protein (TVP) 2-mm particles, and collection bags. Plain water, viscous fluid (30% ultrasound gel solution in water), or water/viscous fluid with TVP were placed in collection bags and drained by gravity through each of the catheters and each connection. The flow rate was measured, recorded, and compared for each catheter and each connection as well as to the control flow rate of the catheters without connections. Ten one-minute trials were performed, and the mean flow rates were analyzed using Student t-test and Pearson correlation coefficient. RESULTS: Flow rate was significantly decreased in the 12-F and 14-F catheters with all stopcock and Luer-Lok connections with both water and viscous fluids. There was no significant reduction in flow for the 8.5-F and 10.2-F catheters with the 2.00-mm, 2.33-mm, and 2.67-mm connections; flow rate was significantly decreased in the 8.5-F and 10.2-F catheters with the 1.33-mm connection. A majority of trials with particulate fluid became occluded, and no consistent pattern between connections could be made. CONCLUSION: This in vitro study suggests that stopcock and Luer-Lok connections limit catheter flow rate when their inner diameter is less than that of the drainage catheter.


Assuntos
Catéteres , Drenagem/instrumentação , Reologia , Desenho de Equipamento , Humanos , Teste de Materiais
13.
Pediatr Diabetes ; 18(4): 320-323, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28318089

RESUMO

Congenital hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or it may present as part of a wider syndrome. For approximately 40%-50% of individuals with this condition, sequence analysis of the known HH genes identifies a causative mutation. Identifying the underlying genetic aetiology in the remaining cases is important as a genetic diagnosis will inform on recurrence risk, may guide medical management and will provide valuable insights into ß-cell physiology. We sequenced the exome of a child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay as well as the unaffected parents. This analysis identified a de novo mutation, p.G403D, in the proband's CACNA1D gene. CACNA1D encodes the main L-type voltage-gated calcium channel in the pancreatic ß-cell, a key component of the insulin secretion pathway. The p.G403D mutation had been reported previously as an activating mutation in an individual with primary hyper-aldosteronism, neuromuscular abnormalities, and transient hypoglycaemia. Sequence analysis of the CACNA1D gene in 60 further cases with HH did not identify a pathogenic mutation. Identification of an activating CACNA1D mutation in a second patient with congenital HH confirms the aetiological role of CACNA1D mutations in this disorder. A genetic diagnosis is important as treatment with a calcium channel blocker may be an option for the medical management of this patient.


Assuntos
Canais de Cálcio Tipo L/genética , Cardiopatias Congênitas/genética , Hiperinsulinismo/genética , Hipoglicemia/genética , Mutação , Doenças Neuromusculares/genética , Substituição de Aminoácidos , Insuficiência da Valva Aórtica/etiologia , Canais de Cálcio Tipo L/química , Canais de Cálcio Tipo L/metabolismo , Análise Mutacional de DNA , Deficiências do Desenvolvimento/etiologia , Feminino , Macrossomia Fetal/etiologia , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/fisiopatologia , Humanos , Hiperinsulinismo/metabolismo , Hiperinsulinismo/fisiopatologia , Hipoglicemia/metabolismo , Hipoglicemia/fisiopatologia , Recém-Nascido , Hipotonia Muscular/etiologia , Doenças Neuromusculares/metabolismo , Doenças Neuromusculares/fisiopatologia
14.
Diabet Med ; 34(7): 1000-1004, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28173619

RESUMO

BACKGROUND: Children with neonatal diabetes often present with diabetic ketoacidosis and hence are at risk of cerebral oedema and subsequent long-term neurological deficits. These complications are difficult to identify because neurological features can also occur as a result of the specific genetic aetiology causing neonatal diabetes. CASE REPORTS: We report two cases of neonatal diabetes where ketoacidosis-related cerebral oedema was the major cause of their permanent neurological disability. Case 1 (male, 18 years, compound heterozygous ABCC8 mutation) and case 2 (female, 29 years, heterozygous KCNJ11 mutation) presented with severe diabetic ketoacidosis at 6 and 16 weeks of age. Both had reduced consciousness, seizures and required intensive care for cerebral oedema. They subsequently developed spastic tetraplegia. Neurological examination in adulthood confirmed spastic tetraplegia and severe disability. Case 1 is wheelchair-bound and needs assistance for transfers, washing and dressing, whereas case 2 requires institutional care for all activities of daily living. Both cases have first-degree relatives with the same mutation with diabetes, who did not have ketoacidosis at diagnosis and do not have neurological disability. DISCUSSION: Ketoacidosis-related cerebral oedema at diagnosis in neonatal diabetes can cause long-term severe neurological disability. This will give additional neurological features to those directly caused by the genetic aetiology of the neonatal diabetes. Our cases highlight the need for increased awareness of neonatal diabetes and earlier and better initial treatment of the severe hyperglycaemia and ketoacidosis often seen at diagnosis of these children.


Assuntos
Edema Encefálico/etiologia , Deficiências do Desenvolvimento/etiologia , Diabetes Mellitus/fisiopatologia , Cetoacidose Diabética/etiologia , Neuropatias Diabéticas/etiologia , Hiperglicemia/etiologia , Quadriplegia/etiologia , Adolescente , Adulto , Edema Encefálico/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Cetoacidose Diabética/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Pessoas com Deficiência , Saúde da Família , Feminino , Humanos , Hiperglicemia/fisiopatologia , Masculino , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Quadriplegia/fisiopatologia , Qualidade de Vida , Índice de Gravidade de Doença , Receptores de Sulfonilureias/genética
15.
Diabetes ; 65(7): 2094-2099, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27207547

RESUMO

Distinguishing patients with monogenic diabetes from those with type 1 diabetes (T1D) is important for correct diagnosis, treatment, and selection of patients for gene discovery studies. We assessed whether a T1D genetic risk score (T1D-GRS) generated from T1D-associated common genetic variants provides a novel way to discriminate monogenic diabetes from T1D. The T1D-GRS was highly discriminative of proven maturity-onset diabetes of young (MODY) (n = 805) and T1D (n = 1,963) (receiver operating characteristic area under the curve 0.87). A T1D-GRS of >0.280 (>50th T1D centile) was indicative of T1D (94% specificity, 50% sensitivity). We then analyzed the T1D-GRS of 242 white European patients with neonatal diabetes (NDM) who had been tested for all known NDM genes. Monogenic NDM was confirmed in 90, 59, and 8% of patients with GRS <5th T1D centile, 50-75th T1D centile, and >75th T1D centile, respectively. Applying a GRS 50th T1D centile cutoff in 48 NDM patients with no known genetic cause identified those most likely to have a novel monogenic etiology by highlighting patients with probable early-onset T1D (GRS >50th T1D centile) who were diagnosed later and had less syndromic presentation but additional autoimmune features compared with those with proven monogenic NDM. The T1D-GRS is a novel tool to improve the use of biomarkers in the discrimination of monogenic diabetes from T1D.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Predisposição Genética para Doença , Mutação , Adolescente , Adulto , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Diagnóstico Diferencial , Feminino , Genótipo , Humanos , Masculino , Adulto Jovem
16.
Diabet Med ; 33(10): 1387-91, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27086753

RESUMO

AIMS: Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the pancreatic KATP channel, cause neonatal diabetes. KCNJ11 is also expressed in the brain, and ~ 20% of those affected have neurological features, which may include features suggestive of psychiatric disorder. No previous studies have systematically characterized the psychiatric morbidity in people with KCNJ11 neonatal diabetes. We aimed to characterize the types of psychiatric disorders present in children with KCNJ11 mutations, and explore their impact on families. METHODS: The parents and teachers of 10 children with neonatal diabetes due to KCNJ11 mutations completed the Strengths and Difficulties Questionnaire and the Development and Wellbeing Assessment. Strengths and Difficulties Questionnaire scores were compared with normative data. Diagnoses from the Development and Wellbeing Assessment were compared with known clinical diagnoses. RESULTS: Strengths and Difficulties Questionnaire scores indicated high levels of psychopathology and impact. Psychiatric disorder(s) were present in all six children with the V59M or R201C mutation, and the presence of more than one psychiatric disorder was common. Only two children had received a formal clinical diagnosis, with a further one awaiting assessment, and the coexistence of more than one psychiatric disorder had been missed. Neurodevelopmental (attention deficit hyperactivity disorder and autism) and anxiety disorders predominated. CONCLUSIONS: Systematic assessment using standardized validated questionnaires reveals a range of psychiatric morbidity in children with KCNJ11 neonatal diabetes. This is under-recognized clinically and has a significant impact on affected children and their families. An integrated collaborative approach to clinical care is needed to manage the complex needs of people with KCNJ11 neonatal diabetes.


Assuntos
Diabetes Mellitus/genética , Diabetes Mellitus/psicologia , Transtornos do Neurodesenvolvimento/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adolescente , Substituição de Aminoácidos , Criança , Transtornos do Comportamento Infantil/complicações , Transtornos do Comportamento Infantil/epidemiologia , Transtornos do Comportamento Infantil/genética , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/genética , Masculino , Mutação de Sentido Incorreto , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/epidemiologia , Manifestações Neurológicas
17.
HIV Med ; 17(3): 222-30, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26919291

RESUMO

OBJECTIVES: Routine HIV screening is recommended in those UK hospitals and primary care settings where the HIV prevalence is > 0.2%. For hepatitis B virus (HBV) and hepatitis C virus (HCV), however, testing is targeted at at-risk groups. We investigated the prevalence of these blood-borne viruses (BBVs) during a routine testing pilot in UK Emergency Departments (EDs). METHODS: During the "Going Viral" campaign (13-19 October 2014), nine UK EDs in areas of high HIV prevalence offered routine tests for HIV, HBV and HCV to adults having blood taken as part of routine care. Patients who tested positive were linked to care. RESULTS: A total of 7807 patients had blood taken during their ED visit; of these, 2118 (27%) were tested for BBVs (range 9-65%). Seventy-one BBV tests were positive (3.4%) with 32 (45.1%) new diagnoses. There were 39 HCV infections (15 newly diagnosed), 17 HIV infections (six newly diagnosed), and 15 HBV infections (11 newly diagnosed). Those aged 25-54 years had the highest prevalence: 2.46% for HCV, 1.36% for HIV and 1.09% for HBV. Assuming the cost per diagnosis is £7, the cost per new case detected would be £988 for HCV, £1351 for HBV and £2478 for HIV. CONCLUSIONS: In the first study in the UK to report prospectively on BBV prevalence in the ED, we identified a high number of new viral hepatitis diagnoses, especially hepatitis C, in addition to the HIV diagnoses. Testing for HIV alone would have missed 54 viral hepatitis diagnoses (26 new), supporting further evaluation of routine BBV testing in UK EDs.


Assuntos
Sangue/virologia , Infecções por HIV/diagnóstico , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Feminino , Infecções por HIV/economia , Infecções por HIV/epidemiologia , Hepatite B/economia , Hepatite B/epidemiologia , Hepatite C/economia , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Estudos Prospectivos , Reino Unido/epidemiologia , Adulto Jovem
18.
HIV Med ; 17(1): 28-35, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26200570

RESUMO

OBJECTIVES: The aim of the study was to identify differences in infant outcomes, virological efficacy, and preterm delivery (PTD) outcome between women exposed to lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r). METHODS: A retrospective case note review was carried out. The case notes of 493 women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during pregnancy and who delivered between 1 September 2007 and 30 August 2012 were reviewed. Data collected included demographics, antiretroviral use, HIV markers, and pregnancy and infant outcomes. Infant outcomes, virological efficacies and PTD rates for LPV/r and ATV/r were compared. RESULTS: A total of 306 women received LPV/r (82 conceiving while on the drug and 224 commencing it post-conception) and 187 received ATV/r (96 conceiving while on the drug and 91 commencing it post-conception). Comparing the two protease inhibitors (PIs), viral suppression rates were similar and, in women starting antiretroviral therapy (ART) post-conception, the median times to first undetectable HIV viral load were not significantly different (P = 0.64). PTD rates did not differ by therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08). Poor fetal outcomes were very uncommon. There were two transmissions, giving a mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05-1.5%). CONCLUSIONS: Both ART regimens were well tolerated and successful in preventing MTCT. No significant differences in tolerability or in pregnancy or infant outcomes were observed, which supports the provision of a choice of PI in pregnancy.


Assuntos
Sulfato de Atazanavir/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , Lopinavir/administração & dosagem , Nascimento Prematuro/epidemiologia , Ritonavir/administração & dosagem , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Sulfato de Atazanavir/farmacologia , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Inibidores da Protease de HIV/farmacologia , Humanos , Lactente , Recém-Nascido , Lopinavir/farmacologia , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Ritonavir/farmacologia , Resultado do Tratamento , Adulto Jovem
19.
Epidemiol Infect ; 143(13): 2837-40, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25672420

RESUMO

An unlinked anonymous study was conducted to estimate the prevalence of hepatitis C virus (HCV) infection in emergency department (ED) attendees at a London Hospital. Nine hundred and ninety-seven samples collected over a 12-day period were tested for HCV antibody (Ab) and reactive samples were further tested for HCV RNA. The HCV seroprevalence was 2·6% (26/997) with 1·2% (12/997) HCV RNA positive. A peak HCV RNA-positive prevalence of 4·8% (3/63) was found in males aged 35-44 years, this was compared to 0% (0/136) in males aged <35 years (P = 0·0614) and 1·4% (4/278) in males aged ⩾45 years (P = 0·2415). Assuming the cost for HCV Ab is £6 and HCV RNA is £40 per test, screening ED attendees aged 25-54 years would cost £360 per viraemic infection and identify 82% of those who were HCV RNA positive, yielding the most favourable cost/benefit ratio. HCV screening of ED attendees aged 25-54 years in this population could be an effective way of identifying patients and limit onward transmission.


Assuntos
Serviço Hospitalar de Emergência , Hepatite C/epidemiologia , Adulto , Feminino , Anticorpos Anti-Hepatite C/sangue , Humanos , Londres/epidemiologia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangue
20.
Br J Radiol ; 88(1047): 20140778, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25587917

RESUMO

OBJECTIVE: To evaluate current UK practice of periprocedural haematological management for image-guided procedures in relation to Cardiovascular and Interventional Radiological Society guidelines, which provide recommendations according to bleeding risk of procedures from Category 1 (lowest) to 3 (highest). METHODS: Survey of practice in UK radiology departments conducted over a 1-year period RESULTS: 48 radiology departments responded. The percentage of departments that stop antithrombotics pre-procedurally are as follows (for Category 1, 2 and 3, respectively): aspirin (31.3%, 43.8%, 54.2%); clopidogrel (54.2%, 68.8%, 72.9%); therapeutic low-molecular-weight heparin (56.3%, 77.1%, 75.0%). The percentage of departments that perform pre-procedural laboratory testing are as follows (for Category 1, 2 and 3, respectively): international normalized ratio (INR; 81.3%, 95.8%, 93.8%); activated partial thrombin time ratio (APTTR; 60.4%, 75.0%, 93.8%); platelet (77.1%, 91.7%, 95.7%); haemoglobin (70.8%, 85.4%, 87.5%). Mean threshold (standard deviation) of laboratory results for conducting procedures (Level 1, 2 and 3, respectively) are as follows: INR [1.53 (0.197), 1.47 (0.186), 1.47 (0.188)]; APTTR [1.50 (0.392), 1.50 (0.339), 1.48 (0.344)]; platelet count (x10(3) cells per microlitre) [74.4 (28.7), 79.9 (29.1), 80.5 (29.3)]; haemoglobin (grams per decilitre) [9.05 (1.40), 9.00 (1.33), 8.92 (1.21)]. No department practices conformed to current recommendations for (1) pre-procedural cessation of antithrombotics and (2) pre-procedural laboratory testing. Two (4.2%) department practices conformed to recommendations for thresholds of haematological parameters. CONCLUSION: Current peri-procedural haematological management is variable and often does not conform to existing recommendations. Further research into the impact of this variation in practice on patient outcome is required. ADVANCES IN KNOWLEDGE: This study demonstrates wide variation in practice in haematological management for image-guided procedures.


Assuntos
Fibrinolíticos/uso terapêutico , Cuidados Pré-Operatórios/métodos , Cirurgia Assistida por Computador , Terapia Trombolítica/métodos , Trombose/prevenção & controle , Feminino , Humanos , Masculino , Contagem de Plaquetas , Prognóstico , Trombose/sangue
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