RESUMO
BACKGROUND: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. OBJECTIVES: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. METHODS: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF-diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One-year all-cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51-74 and >74 years). RESULTS: Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1-year mortality rates (per 100 person-years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64-11.3), 51-74 years (23.3; 22.9-23.7), >74 years (58.5; 57.9-59.0); hazard ratios 245.18 (141.45-424.76), 45.85 (42.77-49.15) and 24.5 (23.64-25.68) for those ≤50, 51-74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%). CONCLUSIONS: Heart failure patients had a higher burden of pre-existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.
Assuntos
Comorbidade , Insuficiência Cardíaca/diagnóstico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVE: Adults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA. METHODS: Participants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over 9 years, hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders. A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality. RESULTS: Deaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI + MOST. Walking 0.2 m/s slower during short- and standard-distance walk tests was associated with 23% (aHR [95%CI]; 1.23 [1.10, 1.39]) and 25% (1.25 [1.09, 1.43]) higher mortality risk, respectively. Walking <0.5 m/s on short-distance and <1.2 m/s standard-distance walk tests, best discriminated those with and without mortality risk. CONCLUSION: Slower walking speed measured via short- and standard-distance walk tests was associated with increased mortality risk in adults with rKOA.
Assuntos
Osteoartrite do Joelho/fisiopatologia , Velocidade de Caminhada/fisiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Estados UnidosRESUMO
Influenza virus infection causes worldwide seasonal epidemics. Although influenza is usually a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in anti-viral responses during influenza. So far, however, IFN regulatory factor (IRF)7 deficiency is the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 swine flu pandemic. By whole exome sequencing we identified two variants, p.R71H and p.P885S, located in the caspase activation and recruitment domain (CARD) and RNA binding domains, respectively, of DExD/H-box helicase 58 (DDX58) encoding the RNA sensor retinoic acid inducible gene 1 (RIG-I). These variants significantly impair the signalling activity of RIG-I. Similarly, patient cells demonstrate decreased antiviral responses to RIG-I ligands as well as increased proinflammatory responses to IAV, suggesting dysregulation of the innate immune response with increased immunopathology. We suggest that these RIG-I variants may have contributed to severe influenza in this patient and advocate that RIG-I variants should be sought in future studies of genetic factors influencing single-stranded RNA virus infections.
Assuntos
Proteína DEAD-box 58/genética , Imunidade Inata/genética , Imunidade Inata/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Adulto , Proteína DEAD-box 58/metabolismo , Humanos , Influenza Humana/patologia , Influenza Humana/virologia , Masculino , Domínios Proteicos/genética , Receptores Imunológicos , Sequenciamento do ExomaRESUMO
OBJECTIVES: Discrimination between HIV-1 and HIV-2 is important to ensure appropriate antiretroviral treatment (ART) and epidemiological surveillance. However, serological tests have shown frequent mistyping when applied in the field. We evaluated two confirmatory tests, INNO-LIA HIV I/II Score and ImmunoComb HIV 1/2 BiSpot, for HIV type discriminatory capacity. METHODS: Samples from 239 ART-naïve HIV-infected patients from the Bissau HIV Cohort in Guinea-Bissau were selected retrospectively based on the initial HIV typing performed in Bissau, ensuring a broad representation of HIV types. INNO-LIA results were interpreted by the newest software algorithm, and three independent observers read the ImmunoComb results. HIV-1/HIV-2 RNA and DNA were measured for confirmation. RESULTS: INNO-LIA results showed 123 HIV-1 positive samples, 69 HIV-2 positive and 47 HIV-1/2 dually reactive. There was agreement between INNO-LIA and HIV-1/HIV-2 RNA and DNA detection, although not all HIV-1/2 dually reactive samples could be confirmed by the nucleic acid results. Overall, the observers found that the ImmunoComb results differed from the INNO-LIA results, with agreements of 90.4, 91.2 and 92.5%, respectively, for HIV-1, HIV-2 and HIV-1/2. The combined kappa-score for agreement between the three observers was 0.955 (z-score 35.1; P < 0.01). Of the HIV-2 mono-reactive samples (INNO-LIA), the three observers interpreted 24.6-31.9% as HIV-1/2 dually infected by ImmunoComb. None of these samples had detectable HIV-1 RNA or DNA. CONCLUSIONS: There was accordance between INNO-LIA calls and nucleic acid results, whereas ImmunoComb overestimated the number of HIV-1/2 dually infected patients. Confirmatory typing is needed for patients diagnosed with HIV-1/2 dual infection by ImmunoComb.
Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Adolescente , Adulto , Algoritmos , Antirretrovirais/uso terapêutico , Feminino , Guiné-Bissau , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Imunoensaio/instrumentação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Especificidade da Espécie , Adulto JovemRESUMO
Herpes simplex encephalitis (HSE) in children has previously been linked to defects in type I interferon production downstream of Toll-like receptor (TLR)3. In the present study, we used whole-exome sequencing to investigate the genetic profile of 16 adult patients with a history of HSE. We identified novel mutations in IRF3, TYK2 and MAVS, molecules involved in generating innate antiviral immune responses, which have not previously been associated with HSE. Moreover, data revealed mutations in TLR3, TRIF, TBK1 and STAT1 known to be associated with HSE in children but not previously described in adults. All discovered mutations were heterozygous missense mutations, the majority of which were associated with significantly decreased antiviral responses to HSV-1 infection and/or the TLR3 agonist poly(I:C) in patient peripheral blood mononuclear cells compared with controls. Altogether, this study demonstrates novel mutations in the TLR3 signaling pathway in molecules previously identified in children, suggesting that impaired innate immunity to HSV-1 may also increase susceptibility to HSE in adults. Importantly, the identification of mutations in innate signaling molecules not directly involved in TLR3 signaling suggests the existence of innate immunodeficiencies predisposing to HSE beyond the TLR3 pathway.
Assuntos
Encefalite por Herpes Simples/genética , Encefalite por Herpes Simples/imunologia , Imunidade Inata , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo , Adulto , Humanos , MutaçãoRESUMO
OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS containing whey (LNS/w), an LNS containing soy (LNS/s) or no LNS. Trough plasma concentrations of efavirenz and nevirapine were measured at 1 and 2 months. Genotyping for 516 G>T and 983 T>C polymorphisms of the cytochrome P450 (CYP) 2B6 locus was performed. Multilevel linear mixed-effects models were used to assess the associations between LNS and plasma efavirenz and nevirapine concentrations. RESULTS: In patients with BMI > 17 kg/m(2), nevirapine concentrations were lower in the LNS/w and LNS/s groups by a median of -2.3 µg/mL [interquartile range (IQR) -3.9; -0.9 µg/mL; P = 0.002] and -2.1 µg/mL (IQR -3.9; -0.9 µg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 µg/mL higher plasma efavirenz concentration compared with the wild type (P < 0.0001), while it was not associated with plasma nevirapine concentrations. CONCLUSIONS: Intake of an LNS was associated with lower plasma nevirapine trough concentrations, indicating possible drug-LNS interactions. The clinical relevance of such reductions in nevirapine exposure is not clear. Plasma efavirenz concentration was not affected by the LNS.
Assuntos
Benzoxazinas/uso terapêutico , População Negra , Ácidos Graxos Essenciais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Nevirapina/sangue , Inibidores da Transcriptase Reversa/sangue , Adulto , Alcinos , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/sangue , Ciclopropanos , Citocromo P-450 CYP2B6/sangue , Suplementos Nutricionais , Etiópia/epidemiologia , Feminino , Infecções por HIV/sangue , Humanos , Lipídeos/administração & dosagem , Lipídeos/sangue , Masculino , Micronutrientes/administração & dosagem , Nevirapina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , População UrbanaRESUMO
During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation.
Assuntos
Músculo Deltoide/metabolismo , Inuíte , Mitocôndrias Musculares/metabolismo , Fosforilação Oxidativa , Músculo Quadríceps/metabolismo , População Branca , Trifosfato de Adenosina/biossíntese , Adulto , Respiração Celular , Temperatura Baixa , DNA Mitocondrial , Músculo Deltoide/citologia , Dinamarca/etnologia , Ácidos Graxos/metabolismo , Feminino , Groenlândia/etnologia , Haplótipos , Humanos , Inuíte/genética , Canais Iônicos/metabolismo , Masculino , Proteínas Mitocondriais/metabolismo , Oxirredução , Consumo de Oxigênio , Músculo Quadríceps/citologia , Estações do Ano , Esqui/fisiologia , Termogênese , Proteína Desacopladora 3 , População Branca/genéticaRESUMO
BACKGROUND: T-wave morphology has been shown to be more sensitive than QT and QTc interval to describe repolarization abnormalities. The electrocardiogram (ECG) performed in athletes may manifest abnormalities, including repolarization alterations. The aim of this study was to investigate the characteristics of T-wave morphology features in athletes. METHODS: Eighty male elite athletes, consisting of 40 Tour de France cyclists (age 27±5years), 40 soccer players (age 26±6years) and 40 healthy men (age 27±5years) were included. RESULTS: Sinus bradycardia, left ventricular (LV) hypertrophy, incomplete right bundle branch block and early repolarization were documented in 25 %, 20%, 13% and 14% of athletes, respectively. ECG criteria for LV hypertrophy in 12-lead ECG were more common in cyclists (35%) than in soccer players (5%), P<0.0001. Cyclists and soccer players had significantly longer RR interval, and repolarization features than the control group. CONCLUSIONS: T-wave morphology of athletes is different from non-athletes, depending of the sport. Decreased potassium current in cardiomyocytes associated with LVH may contribute to these changes.
Assuntos
Desempenho Atlético/fisiologia , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Resistência Física/fisiologia , Esportes/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Comportamento Competitivo/fisiologia , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Recent efforts to develop reliable and efficient early pregnancy screening programmes for pre-eclampsia have focused on combining clinical, biochemical and biophysical markers. The same model has been used for first-trimester screening for fetal aneuploidies i.e. prenatal diagnosis (PD), which is routinely offered to all pregnant women in many developed countries. Some studies suggest combining PD and pre-eclampsia screening, so women can be offered testing for a number of conditions at the same clinical visit. A combination of these tests may be practical in terms of saving time and resources; however, the combination raises ethical issues. First-trimester PD and pre-eclampsia screening entail qualitative differences which alter the requirements for disclosure, non-directedness and consent with regard to the informed consent process. This article explores the differences related to the ethical issues raised by PD and pre-eclampsia in order to elucidate which factors are relevant to deciding the type of information and consent required in each context from the perspective of the ethical principles of beneficence and autonomy. Furthermore, it argues that ensuring respect for patient autonomy is context dependent and, consequently, pre-eclampsia screening and PD should be performed independently of one another.
Assuntos
Técnicas de Apoio para a Decisão , Ética Médica , Pré-Eclâmpsia/diagnóstico , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal/ética , Feminino , Promoção da Saúde/métodos , Humanos , Programas de Rastreamento/ética , Programas de Rastreamento/métodos , Gravidez , Diagnóstico Pré-Natal/métodosRESUMO
OBJECTIVE: To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), and to examine the role of hyperandrogenaemia. DESIGN: Cohort study. SETTING: Singleton pregnancies in women with PCOS identified at a private fertility clinic during 1997-2010 and a background population including all singleton deliveries at Hvidovre Hospital, Denmark, in 2005. POPULATION: A cohort of 459 women with PCOS and a background population of 5409 women. METHODS: Obstetric outcomes were extracted from national Danish registries and odds ratios (ORs) were calculated by multiple logistic regression analysis, adjusting for age, parity, and body mass index. MAIN OUTCOME MEASURES: Risk of pre-eclampsia, preterm delivery, and small for gestational age offspring in the entire PCOS population and in a subsample with hyperandrogenaemia. RESULTS: Women with PCOS had an increased risk of preterm delivery <37 weeks of gestation (OR 2.28; 95% confidence interval, 95% CI, 1.51-3.45; P < 0.0001). The elevated risk was confined to hyperandrogenic women with PCOS: preterm delivery before 37 weeks of gestation (OR 2.78; 95% CI 1.62-4.77; P < 0.0001), and was not seen in normoandrogenic women with PCOS (OR 1.35; 95% CI 0.54-3.39; P = 0.52). The overall risk of pre-eclampsia was not elevated (OR 1.69; 95% CI 0.99-2.88; P = 0.05) compared with the background population, but was significantly increased in the hyperandrogenic subsample (OR 2.41; 95% CI 1.26-4.58; P < 0.001). The risk of small for gestational age offspring was similar in all groups. CONCLUSION: Women with PCOS had an increased risk of preterm delivery compared with the background population. The increased risk was confined to hyperandrogenic women with PCOS who had a two-fold increased risk of preterm delivery and pre-eclampsia.
Assuntos
Hiperandrogenismo/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Pré-Eclâmpsia/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Idade Materna , Paridade , Gravidez , Análise de RegressãoRESUMO
OBJECTIVE: Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD-negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD-negative women who carry an RhD-positive fetus. Here, we present a 2-year evaluation of a nationwide prenatal RHD screening. METHODS: Blood samples were drawn from RhD-negative women in gestational week 25. DNA was extracted from maternal plasma and analyzed for the RHD gene. The prenatal RHD results were compared with the serological typing of newborns in 12,668 pregnancies. Early compliance was assessed for 690 pregnancies. RESULTS: The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD were not detected in 11 pregnancies (0.087%). The sample uptake percentage was 84.2%, and the compliance for prenatal anti-D administration was 93.2%. CONCLUSION: The high sensitivity, maintained over 2 years, underlines the reliability of routine prenatal fetal RHD screening in RhD-negative pregnant women, specifically at 25 weeks of gestation. The remaining challenges are logistical and are related to program compliance.
Assuntos
Proteínas Fetais/sangue , Testes para Triagem do Soro Materno/estatística & dados numéricos , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Dinamarca , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2, two homologous metzincin metalloproteases, are both tightly linked to regulation within the insulin-like growth factor (IGF) system because of their specific cleavage of IGF binding proteins. Recent studies suggest that PAPP-A may be involved in clinical conditions related to unwanted cellular growth, and the circulating levels of PAPP-A is an established biomarker in prenatal screening for chromosomal abnormalities. Microarray data indicate that PAPP-A2 has potential as a biomarker for pre-eclampsia. However, well-characterized immunological methods of quantification are not available. We therefore developed monoclonal antibodies against recombinant PAPP-A2. The antibodies were epitope mapped against recombinantly expressed chimeras between PAPP-A2 and PAPP-A. Furthermore, circulating PAPP-A2 was immunoaffinity purified and characterized by sequence analysis and mass spectrometry. Unlike PAPP-A, PAPP-A2 is a noncovalent dimer in which each subunit of 1558 amino acids originates from all of the 22 predicted coding exons. A previously hypothesized variant (PAPP-E) does not exist, but low amounts of a C-terminally truncated PAPP-A2 variant was detected. A sensitive and robust ELISA for full-length PAPP-A2 was developed and used to establish normal ranges of PAPP-A2 through pregnancy. The functional sensitivity of this ELISA at 20% CV was 0.08 ng/ml, and the serum concentration of PAPP-A2 was found to increase during pregnancy in agreement with placental synthesis. The existence of this assay will enable an assessment of the biomarker potential of PAPP-A2 in pre-eclampsia as well as other clinical conditions.
Assuntos
Proteína Plasmática A Associada à Gravidez/análise , Gravidez/sangue , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/normas , Animais , Antígenos/sangue , Biomarcadores/sangue , Feminino , Doenças Fetais/sangue , Doenças Fetais/diagnóstico , Células HEK293 , Humanos , Imunoensaio/métodos , Camundongos , Camundongos Knockout , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. OBJECTIVE: To investigate the association between tau protein concentration and 14-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review. METHODS: A total of 66 patients with MS and/or ON from the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. RESULTS: The study shows a significantly increased concentration of tau protein in CSF from patients with relapsing-remitting MS and patients monosymptomatic at onset who progressed to MS, but interestingly no increased tau protein concentration in monosymptomatic ON. The concentration of tau protein was significantly correlated to Expanded Disability Status Scale score. No 14-3-3 protein was detected in any CSF sample. CONCLUSIONS: The results of this study invite further exploration of the possible role of tau protein as a prognostic factor to predict progression from ON to MS in future studies.
Assuntos
Encéfalo/metabolismo , Esclerose Múltipla/líquido cefalorraquidiano , Neurite Óptica/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Proteínas 14-3-3/líquido cefalorraquidiano , Adulto , Biomarcadores/líquido cefalorraquidiano , Dinamarca , Avaliação da Deficiência , Progressão da Doença , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Neurite Óptica/diagnóstico , Prognóstico , Índice de Gravidade de Doença , Fatores de Tempo , Regulação para Cima , Adulto JovemRESUMO
Prospective surveillance of CreutzfeldtJakob disease (CJD) was initiated in Denmark in 1997, following the observation of variant CJD in the United Kingdom. Demographic, clinical and diagnostic information was collected for each patient with clinical suspicion of CJD. Here we describe the methods for surveillance and the observed outcomes between 1 January 1997 and 31 December 2008. A total of 83 patients were classified as sporadic CJD, 47 were definite diagnoses, 34 probable and two possible. This resulted in a mean incidence of 1.26 patients with probable and definite sporadic CJD per million inhabitants. Two sporadic CJD patients were found to have a genetic variant of unknown significance: Thr201Ser and Glu200Asp. One patient was diagnosed with Gerstmann-Sträussler-Scheinker syndrome. No patients were classified as having variant, iatrogenic or familial CJD. The Danish surveillance system, like those in other countries, has a multidisciplinary approach, which is labour-intensive and time-consuming but ensures the most complete set of information possible. With this approach we think that patients with variant CJD would have been detected had they occurred in Denmark. Certain aspects of CJD surveillance need further discussion at European level and beyond, in order to find a balance between efficiency of the systems and accuracy of surveillance data.
Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Síndrome de Creutzfeldt-Jakob/genética , Dinamarca/epidemiologia , Notificação de Doenças/estatística & dados numéricos , Eletroencefalografia , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Vigilância da População , Estudos Prospectivos , Distribuição por Sexo , Inquéritos e QuestionáriosRESUMO
PURPOSE: The aim is to explore patient satisfaction with nurse-led consultations and the health care professionals' experiences on the expanded scope of nursing practice. METHODS: A sequential multi-methods study is comprised of a study-specific questionnaire to patients with gynecological- or breast cancer followed by a survey among the involved physicians. Finally, two focus group interviews explored the perspectives of clinical nurse specialists. RESULTS: Study participants were patients (n = 109), physicians (n = 12) and clinical nurse specialists (n = 10). Patients expressed that their concerns and questions were addressed, and even sensitive and very personal issues were discussed. They reported that they were able to follow self-management strategies to cope with side effects (89.8%) and emotional reactions (68.8%). The clinical nurse specialists described how they sought to embrace a person-centred approach in the consultations. The expanded scope of nursing practice resulted in enhanced feelings of professionalism. The physicians appreciated the clinical nurse specialists' skills and competencies and were comfortable referring patients to nurse-led consultations. CONCLUSIONS: Nurse-led consultations are in a pivotal position to establish a culture for person-centred nursing practice. We recommend developing a strategy for implementation of nurse-led consultations and to clarify and align expectations between the involved. Nurse-led consultations have the potential to offer quality-of-care and increase clinical nurse specialists' professional identity and job satisfaction.
Assuntos
Enfermeiros Clínicos , Médicos , Padrões de Prática em Enfermagem , Humanos , Encaminhamento e Consulta , Satisfação do PacienteRESUMO
Biohybrid bacteria-based microrobots are increasingly recognized as promising externally controllable vehicles for targeted cancer therapy. Magnetic fields in particular have been used as a safe means to transfer energy and direct their motion. Thus far, the magnetic control strategies used in this context rely on poorly scalable magnetic field gradients, require active position feedback, or are ill-suited to diffuse distributions within the body. Here, we present a magnetic torque-driven control scheme for enhanced transport through biological barriers that complements the innate taxis toward tumor cores exhibited by a range of bacteria, shown for Magnetospirillum magneticum as a magnetically responsive model organism. This hybrid control strategy is readily scalable, independent of position feedback, and applicable to bacterial microrobots dispersed by the circulatory system. We observed a fourfold increase in translocation of magnetically responsive bacteria across a model of the vascular endothelium and found that the primary mechanism driving increased transport is torque-driven surface exploration at the cell interface. Using spheroids as a three-dimensional tumor model, fluorescently labeled bacteria colonized their core regions with up to 21-fold higher signal in samples exposed to rotating magnetic fields. In addition to enhanced transport, we demonstrated that our control scheme offers further advantages, including the possibility for closed-loop optimization based on inductive detection, as well as spatially selective actuation to reduce off-target effects. Last, after systemic intravenous injection in mice, we showed significantly increased bacterial tumor accumulation, supporting the feasibility of deploying this control scheme clinically for magnetically responsive biohybrid microrobots.
Assuntos
Neoplasias , Robótica , Camundongos , Animais , Torque , Campos Magnéticos , Movimento (Física)RESUMO
OBJECTIVES: Our aim was to evaluate the effect of fetal sex, smoking and body mass index (BMI) on nuchal translucency (NT). METHODS: We analyzed data from 7,357 women with a normal singleton live birth outcome with information on smoking, BMI and sex of the infant. NT measurements were converted to multiples of the median (MoM(NT)) using a previously reported linear regression analysis. RESULTS: The odds ratio (OR) for MoM(NT) >95th centile was 1.5 (95% CI 1.2-1.9) for smokers compared to nonsmokers and 1.4 (95% CI 1.1-1.7) for male fetuses compared to female fetuses. Obese women (BMI ≥30) had an increased OR for a large NT of 1.7 (95% CI 1.2-2.6) compared to normal weight women. Obese smokers carrying a male fetus had an OR of 4.2 (95% CI 1.7-10.1) of a MoM(NT) >95th centile compared to normal weight nonsmoking women with a female fetus. The effects of smoking, obesity status and fetal sex were independent of each other. CONCLUSIONS: Smoking, obesity and male sex are associated to a MoM(NT) >95th centile. This may affect screening performance and entail unnecessary anxiety in these women. Further investigations, including fetuses with adverse outcome, are needed.