RESUMO
Aquatic ecosystems have been devastated by the continued persistence of the synthetic estrogen compounds ß-estradiol and 17α-ethynylestradiol. Common wastewater treatment methods do not reduce these compounds in effluent below problematic concentrations. An emerging cost-effective solution to this problem is the use of constructed wetlands to remove these estrogen compounds. This study analyzed the ability of duckweed (Lemna minor), water hyacinth (Eichhornia crassipes), and water cabbage (Pistia stratiotes) to remove ß-estradiol and 17α-ethynylestradiol through the use of bench-scale constructed wetlands over a 15-week period. Estrogen concentration in water was collected over time along with plant nutrient content, contaminant extractions, and media extractions. Results indicated that estrogen concentration was reduced by the plants and soil media. Duckweed was the most effective at 96% removal, followed by water hyacinth at 72% removal, then water cabbage at 35% removal, and lastly sediment media at 9% removal. This study provides evidence for the ability of constructed wetlands to be used as a means to remove estrogen compounds from wastewater and demonstrates differences in plants removal efficiencies, with duckweed being the most effective of the selected plants.
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Araceae , Eichhornia , Poluentes Químicos da Água , Biodegradação Ambiental , Ecossistema , Estradiol , Estrogênios , Etinilestradiol , Águas Residuárias , Poluentes Químicos da Água/análise , Áreas AlagadasRESUMO
BACKGROUND: First-generation antihistamines (FGAs) are classified as 'potentially inappropriate' for use in older patients (patients aged ≥ 65 years). However, the prevalence of and factors associated with FGA prescription have not been studied. OBJECTIVES: To examine FGA prescription rates for older patients who visited dermatology offices, and compare them to those for younger patients (patients aged 18-65 years) who visited dermatology offices and those for older patients who visited primary-care physicians (PCPs). METHODS: This was a multiyear cross-sectional observational study using data from the U.S. National Ambulatory Medical Care Survey (2006-2015). Visits by patients aged 18 years or older were included in the study; the data comprised 15 243 dermatology office visits and 66 036 PCP office visits. The main outcome was FGA prescription. Other variables included physician specialty (dermatologist or PCP), patient's age, diagnosis of dermatological conditions and reason for visit. RESULTS: For dermatology visits, the overall FGA prescription rate for older patients was similar to that for younger patients (1·5% vs. 1·2%; P = 0·19), even when the diagnosis was dermatitis or pruritus (3·7% vs. 4·8%; P = 0·21) or when itch was a complaint (7·6% vs. 6·7%; P = 0·64). However, the rate of FGA prescription for dermatology visits was lower than that for PCP visits, in analyses matched for patient and visit characteristics (3·9% vs. 7·4%; P = 0·02). CONCLUSIONS: Our findings suggest that FGAs are overprescribed to older patients but that dermatologists are less likely to prescribe FGAs than PCPs. What's already known about this topic? First-generation antihistamines (FGAs) have been shown to pose substantial risks to older adults, including cognitive impairment, falls, confusion, dry mouth and constipation. Therefore, FGAs have been classified as 'potentially inappropriate' for use in older patients by the American Geriatrics Society. It has also been shown that dermatologists do not always take patient characteristics (e.g. age or life expectancy) into account when deciding on a treatment, instead following a 'one-size-fits-all' approach. What does this study add? FGAs are often prescribed during dermatology visits, and prescription rates do not differ between older and younger patients. There were no significant differences in prescription rates when comparing younger and older adults with the same diagnosis or symptom (e.g. dermatitis, pruritus or itch). FGAs are prescribed at higher rates in primary-care offices than in dermatology offices.
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Antagonistas dos Receptores Histamínicos H1 , Dermatopatias , Adolescente , Adulto , Idoso , Estudos Transversais , Pesquisas sobre Atenção à Saúde , Humanos , Pessoa de Meia-Idade , Visita a Consultório Médico , Padrões de Prática Médica , Estados Unidos/epidemiologia , Adulto JovemRESUMO
PURPOSE: Limited data about oral mucositis (OM) in stem cell transplant patients with underlying hematological disease is available in Germany. The purpose of this feasibility study was to determine the incidence, treatment patterns, patients' adherence, and costs of OM. METHODS: Prospective, noninterventional single-center observational study. INCLUSION CRITERIA: allogenic/autologous stem cell transplant patients ≥ 18 years, high-dose chemotherapy. OM assessment: WHO Oral Toxicity Scale. Adherence was measured in patient interviews. Preventive and therapeutic measures were extracted from patients' charts. RESULTS: Forty-five patients (25 allogenic, 20 autologous) were enrolled. Twenty-six (58%) patients developed OM (54% grade I/II, 46% grade III/IV). Age ≥ 65 (31% vs 69%, p = 0.021) was associated with a lower OM incidence. A positive history of smoking (1.77 vs 2.69, p = 0.036) was associated with a lower OM grade, patients with unrelated donors (2.63 vs 1.29, p = 0.014) were associated with higher OM grades and females (80% vs 47%, RR = 1.71, p = 0.035) with a higher incidence. OM patients were less adherent to recommended daily mouth rinses (35% vs 68%, p = 0.027). More analgesic treatment (80% vs 32%, p = 0.001) and intravenous opioids (24% vs 0%, p = 0.023) were prescribed in OM patients. Total drug treatment and nutrition costs were 824 (p = 0.037) higher in autologous transplanted patients. CONCLUSION: Initial risk and consecutive OM assessment, determination of patients' adherence, resource consumption, and costs are prerequisites to evaluate OM care. In the best case, several centers will follow the same methodological approach and the collected data will serve as a basis for benchmarking analyses to optimize OM care where required.
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Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Estomatite/epidemiologia , Adulto , Efeitos Psicossociais da Doença , Estudos de Viabilidade , Feminino , Alemanha/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/economia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/administração & dosagem , Cooperação do Paciente/estatística & dados numéricos , Estudos Prospectivos , Índice de Gravidade de Doença , Estomatite/tratamento farmacológico , Estomatite/economia , Estomatite/etiologia , Transplante Autólogo , Adulto JovemRESUMO
BACKGROUND: The prevalence of olfactory impairment increases with age and is known to be an early sign of different neurodegenerative diseases. Only few population-based studies examined the prevalence of olfactory impairment and comparisons across studies are scarce. Aim of this analysis was to compare the prevalence and determinants of normosmia across five population based studies in Germany. METHODOLOGY: Data from five population-based, cross-sectional studies were included. They were independently conducted and used the same test system (Sniffin' Sticks Screening 12) to measure olfactory function. This system consists of 12 odor-dispensing felt-tip pens; the task is a forced-choice selection among four alternative odors per pen. Sociodemographic information and comorbidities were assessed in face-to-face interviews. Univariate, descriptive statistics and multivariable logistic regression models stratified by study, were performed to determine risks, i.e. prevalence odds ratios, associated with olfactory function. RESULTS: The prevalence of normosmic participants varied considerably across studies. Olfactory function was lower in men, decreased with age, and increased with higher education. Several individual comorbidities and a comorbidity index were associated with olfactory dysfunction. Recognition performance for three of the 12 pens was especially low in all studies. CONCLUSION: Four factors, well known to describe population composition, contribute to explain differences in the prevalence of olfactory function between studies when the same test system is used. Our results indicate that comorbidities and educational level should always be considered when test systems based on smell recognition are used in population-based studies.
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Transtornos do Olfato , Olfato , Estudos Transversais , Alemanha , Humanos , Masculino , Odorantes , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Due to the necessity for lifelong treatment, high costs for the healthcare system and changes in role expectations of patients towards physicians, multiple sclerosis (MS) is an important topic in healthcare research. OBJECTIVE: The aim of this review is to provide an overview of the current study situation in Germany in 2020 on utilization of outpatient medical resources and shared decision making in patients with MS. MATERIAL AND METHODS: For this review a literature search was carried out in PubMed and other extended sources in order to identify and present relevant publications. RESULTS: There are only a few studies on the utilization of outpatient medical resources by patients with MS in Germany. The highest values for utilization were found for general practitioners, family physicians and neurologists whereas urologists were less frequently involved. The values for the utilization of services provided by physiotherapists greatly differed between the studies. Several studies using different approaches to shared decision making in Germany were identified and summarized. An important prerequisite for shared decision making is an adequate knowledge on the side of the patients. CONCLUSION: Differences in the utilization of outpatient resources by MS patients in Germany can be explained by methodological differences and limitations of the individual studies. The use of shared decision making by MS patients is demanded by various parties but so far there is little evidence for a positive effect on the disease.
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Tomada de Decisão Compartilhada , Esclerose Múltipla , Médicos , Assistência Ambulatorial , Alemanha , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Participação do PacienteRESUMO
In this overview the current quality of acute in-hospital care of stroke patients in Germany in 2018 is described based on standardized and evidence-based quality indicators. For this purpose the reports of the regional quality assurance projects for stroke care, which collaborated within the German-speaking Stroke Registers Study Group (ADSR) were analyzed. Overall, more than 280,000 acute admissions of stroke patients were documented in the included quality assurance projects. The results regarding the defined 16 quality indicators comprising diagnostics, acute treatment, rehabilitation and secondary prevention showed a high level of acute inpatient treatment of stroke in Germany. Only a few quality indicators, such as early transfer for thrombectomy indicated a great necessity for process optimization.
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Isquemia Encefálica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Alemanha , Humanos , Qualidade da Assistência à Saúde , Sistema de Registros , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND AND PURPOSE: In contrast to anterior circulation stroke (ACS), there is no evidence from randomized trials that mechanical thrombectomy (MT) with modern stent retrievers or thromboaspiration is safe and effective in posterior circulation stroke (PCS). METHODS: The present analysis was based on the prospective multicentre Registry on Revascularization in Ischemic Stroke Patients (REVASK) in Germany. Demographic data, periprocedural times and complications, recanalization rates, and functional outcome at discharge and after 3 months were compared between 139 consecutive patients with PCS (84.9% basilar artery, 16.5% vertebral artery and 4.3% posterior cerebral artery occlusion) and 961 patients with ACS treated with MT. RESULTS: Compared to ACS, PCS patients were significantly younger (65 vs. 69 years, P = 0.021) and had a lower median National Institutes of Health Stroke Scale (NIHSS) score at baseline (12 vs. 15, P = 0.024). Patients with PCS had a significantly longer time delay between symptom onset and both start and end of the MT procedure. Successful recanalization and thrombectomy passes did not significantly differ between the two groups. No symptomatic intracranial haemorrhage occurred in PCS compared to 3% in ACS (P = 0.010). The median NIHSS score at discharge was 3 in PCS and 4 in ACS. Favourable functional outcome at 3 months (modified Rankin Scale 0-2 38.0% vs. 42.6%, P = 0.392) and mortality (33.7% vs. 30.8%, P = 0.539) did not differ significantly between PCS and ACS. CONCLUSIONS: The study suggests that MT in PCS shows a lower risk of symptomatic intracranial haemorrhage and similar effectiveness compared to ACS. PCS patients also seem to benefit from MT started beyond 6 h after symptom onset.
Assuntos
Arteriopatias Oclusivas/cirurgia , Isquemia Encefálica/cirurgia , Artéria Cerebral Posterior/cirurgia , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/complicações , Isquemia Encefálica/etiologia , Avaliação da Deficiência , Feminino , Alemanha , Humanos , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Stents , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.
Assuntos
Substância Cinzenta/anatomia & histologia , Substância Cinzenta/fisiologia , Obesidade/genética , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/fisiologia , Adulto , Algoritmos , Índice de Massa Corporal , Mapeamento Encefálico/métodos , Feminino , Predisposição Genética para Doença , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Obesidade/etiologia , Obesidade/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Fatores de RiscoRESUMO
INTRODUCTION AND AIM: Open questions in haemophilia, such as effectiveness of innovative therapies, clinical and patient-reported outcomes (PROs), epidemiology and cost, await answers. The aim was to identify data attributes required and investigate the availability, appropriateness and accessibility of real-world data (RWD) from German registries and secondary databases to answer the aforementioned questions. METHODS: Systematic searches were conducted in BIOSIS, EMBASE and MEDLINE to identify non-commercial secondary healthcare databases and registries of patients with haemophilia (PWH). Inclusion of German patients, type of patients, data elements-stratified by use in epidemiology, safety, outcomes and health economics research-and accessibility were investigated by desk research. RESULTS: Screening of 676 hits, identification of four registries [national PWH (DHR), national/international paediatric (GEPARD, PEDNET), international safety monitoring (EUHASS)] and seven national secondary databases. Access was limited to participants in three registries and to employees in one secondary database. One registry asks for PROs. Limitations of secondary databases originate from the ICD-coding system (missing: severity of haemophilia, presence of inhibitory antibodies), data protection laws and need to monitor reliability. CONCLUSION: Rigorous observational analysis of German haemophilia RWD shows that there is potential to supplement current knowledge and begin to address selected policy goals. To improve the value of existing RWD, the following efforts are proposed: ethical, legal and methodological discussions on data linkage across different sources, formulation of transparent governance rules for data access, redefinition of the ICD-coding, standardized collection of outcome data and implementation of incentives for treatment centres to improve data collection.
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Pesquisa Biomédica , Bases de Dados Factuais , Hemofilia A/terapia , Sistema de Registros , Adulto , Criança , Alemanha , Humanos , Resultado do TratamentoRESUMO
INTRODUCTION: The implementation of early long-term, regular clotting factor concentrate (CFC) replacement therapy ('prophylaxis') has made it possible to offer boys with haemophilia a near normal life. Many different regimens have reported favourable results, but the optimum treatment regimens have not been established and the cost of prophylaxis is very high. Both for optimizing treatment and reimbursement issues, there is a need to provide objective evidence of both short- and long-term results and benefits of prophylactic regimens. AIMS: This report presents a critical review of outcome measures for use in the assessment of musculoskeletal health in persons with haemophilia according to the International Classification of Functioning, Disability and Health (ICF). This framework considers structural and functional changes, activities and participation in a context of both personal and environmental factors. METHODS: Results were generated by a combination of a critical review of available literature plus expert opinion derived from a two day consensus conference between 48 health care experts from different disciplines involved in haemophilia assessment and care. Outcome tools used in haemophilia were reviewed for reliability and validity in different patient groups and for resources required. RESULTS AND CONCLUSION: Recommendations for choice of outcome tools were made according to the ICF domains, economic setting, and reason for use (clinical or research). The next step will be to identify a 'core' set of outcome measures for use in clinical care or studies evaluating treatment.
Assuntos
Hemofilia A/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , HumanosRESUMO
INTRODUCTION: Studies on the prevalence of cardiovascular disease (CVD) and risk factors in patients with haemophilia (PWH) in comparison to the general population have generated inconsistent results. The ADVANCE Working Group collected data on CV comorbidities in PWH aged ≥40 years (H(3) Study). AIM: Identification of German epidemiological data on CVD for the general population, evaluation for appropriateness, and execution of comparisons with PWH. METHODS: Identification of data sources by structured literature (EMBASE, MEDLINE) searches. INCLUSION CRITERIA: German general population, CVD and risk factors, gender/age stratification, sample size >500 male persons, age groups ≥40 years, current data collection, language English/German. Comparison of data on CVD and risk factors in PWH (H(3) Study) with published German general population data. RESULTS: Criteria for data source appropriateness were defined. Of five national and three international epidemiological studies, the DEGS1 Study (German Health Interview and Examination Survey for Adults) was identified as the most suitable comparator. Compared with men from DEGS1, hypertension was significantly more prevalent in PWH aged 50-59 years (41.7% [95% CI: 37.3-46.2] vs. 52.0% [95% CI: 43.7-60.1], P = 0.03). Coronary artery/heart disease (CHD) was significantly less prevalent in PWH aged ≥60 years (60-69 years: 19.5% [95% CI: 15.9-23.7] vs. 8.1% [95% CI: 3.3-16.1], P = 0.02; 70-79 years: 30.5% [95% CI: 25.9-35.5] vs. 11.8% [95% CI: 5.2-21.9], P = 0.002). No statistically significant difference for ischaemic cerebrovascular disease/stroke was detected. CONCLUSION: Increased prevalence of hypertension in PWH should trigger regular screening. CHD does occur in PWH aged ≥60 years though apparently with lower prevalence. Given the growing population of elderly PWH, guidelines for prevention and treatment of CVD should be developed.
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Doenças Cardiovasculares/epidemiologia , Hemofilia A/epidemiologia , Hemofilia B/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Analysis of data pooled from multiple phase 2 (SILEN-C1 to 3) and phase 3 studies (STARTVerso1 to 4) of the hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) protease inhibitor faldaprevir plus pegylated interferon alpha/ribavirin (PR) provides a comprehensive evaluation of baseline and treatment-emergent NS3/4A amino acid variants among HCV genotype-1 (GT-1)-infected patients. Pooled analyses of GT-1a and GT-1b NS3 population-based pretreatment sequences (n = 3,124) showed that faldaprevir resistance-associated variants (RAVs) at NS3 R155 and D168 were rare (<1%). No single, noncanonical NS3 protease or NS4A cofactor baseline polymorphism was associated with a reduced sustained virologic response (SVR) to faldaprevir plus PR, including Q80K. The GT-1b NS3 helicase polymorphism T344I was associated with reduced SVR to faldaprevir plus PR (P < 0.0001) but was not faldaprevir specific, as reduced SVR was also observed with placebo plus PR. Among patients who did not achieve SVR and had available NS3 population sequences (n = 507 GT-1a; n = 349 GT-1b), 94% of GT-1a and 83% of GT-1b encoded faldaprevir treatment-emergent RAVs. The predominant GT-1a RAV was R155K (88%), whereas GT-1b encoded D168 substitutions (78%) in which D168V was predominant (67%). The novel GT-1b NS3 S61L substitution emerged in 7% of virologic failures as a covariant with D168V, most often among the faldaprevir breakthroughs; S61L in combination with D168V had a minimal impact on faldaprevir susceptibility compared with that for D168V alone (1.5-fold difference in vitro). The median time to loss of D168 RAVs among GT-1b-infected patients who did not have a sustained virologic response at 12 weeks posttreatment (non-SVR12) after virologic failure was 5 months, which was shorter than the 14 months for R155 RAVs among GT-1a-infected non-SVR12 patients, suggesting that D168V is less fit than R155K in the absence of faldaprevir selective pressure.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Polimorfismo Genético , Ribavirina/uso terapêutico , Tiazóis/uso terapêutico , Substituição de Aminoácidos , Ácidos Aminoisobutíricos , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Método Duplo-Cego , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Expressão Gênica , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatite C Crônica/virologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Leucina/análogos & derivados , Mutação , Prolina/análogos & derivados , Quinolinas , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismoRESUMO
AIM: To analyse the association of neighbourhood unemployment with incident self-reported physician-diagnosed Type 2 diabetes in a population aged 45-74 years from five German regions. METHODS: Study participants were linked via their addresses at baseline to particular neighbourhoods. Individual-level data from five population-based studies were pooled and combined with contextual data on neighbourhood unemployment. Type 2 diabetes was assessed according to a self-reported physician diagnosis of diabetes. We estimated proportional hazard models (Weibull distribution) in order to obtain hazard ratios and 95% CIs of Type 2 diabetes mellitus, taking into account interval-censoring and clustering. RESULTS: We included 7250 participants residing in 228 inner city neighbourhoods in five German regions in our analysis. The incidence rate was 12.6 per 1000 person-years (95% CI 11.4-13.8). The risk of Type 2 diabetes mellitus was higher in men [hazard ratio 1.79 (95% CI 1.47-2.18)] than in women and higher in people with a low education level [hazard ratio 1.55 (95% CI 1.18-2.02)] than in those with a high education level. Independently of individual-level characteristics, we found a higher risk of Type 2 diabetes mellitus in neighbourhoods with high levels of unemployment [quintile 5; hazard ratio 1.72 (95% CI 1.23-2.42)] than in neighbourhoods with low unemployment (quintile 1). CONCLUSIONS: Low education level and high neighbourhood unemployment were independently associated with an elevated risk of Type 2 diabetes mellitus. Studies examining the impact of the residential environment on Type 2 diabetes mellitus will provide knowledge that is essential for the identification of high-risk populations.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Características de Residência/estatística & dados numéricos , Desemprego/estatística & dados numéricos , Idoso , Escolaridade , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores SocioeconômicosRESUMO
Payers in European countries request studies with high levels of evidence for decision making also for rare diseases like haemophilia B (HB). The objective of the study was to determine the status quo of current studies in HB regarding the overall level of evidence generated. The methods used for performing the study were systematic literature research in EMBASE and MEDLINE, search terms 'HB' and 'factor IX' (FIX). The inclusion criteria were journal articles (JA), conference abstracts (CA), English language, published between January 2009 and March 2013, studies only; screening of titles, abstracts, full texts subsequently. ClinicalTrials.gov search: unpublished registered trials (RT) concerning HB or FIX. The analysis was performed on research topic, sponsor, recruitment status and study design. Screening of 1639 hits yielded 31 JA describing 35 studies, and 62 CA. FIX was subject of 21 studies (60.0%) and 29 CA (46.8%). Seven studies focused on various aspects of HB, six on haemophilia studies with separate HB data. Screening of 173 hits from ClinicalTrials.gov yielded 42 RT. Overall, 32 RT (76.2%) related to FIX. Measurement of health-related quality of life (HRQoL) was identified in none of these studies, four CA (6.5%), four RT (9.5%). Randomized study design was found in one study (2.9%), four RT (9.5%). Three studies (8.6%) and seven RT (16.7%) were prospective, observational and comparative. The majority of published clinical studies do not meet payers' expectations for evidence. Therefore, clinical investigation concepts addressing randomization, outcomes research including HRQoL and comparison of therapy options should be discussed. Refined statistical methods and exploitation of complementary real-life data sources may fill current evidence gaps concerning rare diseases.
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Hemofilia B , Humanos , Qualidade de Vida , Doenças RarasRESUMO
BACKGROUND: Hypersensitivity to light, noise and odour are pivotal clinical characteristics of migraine associated with enhanced cortical excitability and dysfunctional habituation. However, little is known about the integrity of basic sensory functioning in migraine on a population-based level. METHODS: A total of 129 participants with migraine (105 without aura, MwoA, 24 with aura, MA) and 522 healthy controls without headache 12 months prior to baseline were included from a sample of the DMKG study and underwent standardised clinical sensory testing of smell, taste, hearing and vision. RESULTS: After adjustment for age, sex, smoking status and history of head injuries, the chance of impaired colour perception was significantly higher in MA compared to controls (odds ratio, OR=3.20; 95% CI=1.20-8.53) and MwoA (OR=3.62; 95% CI=1.31-9.97). Compared to MwoA, MA also had an increased chance of smell (OR=3.20; 95% CI=0.98-10.42) and taste (OR=2.58; 95% CI=0.90-7.40) impairment. CONCLUSIONS: In this cross-sectional, population-based study on sensory functioning in migraine participants, colour vision was impaired interictally in MA compared to MwoA and controls.
Assuntos
Defeitos da Visão Cromática/etiologia , Enxaqueca com Aura/complicações , Enxaqueca com Aura/fisiopatologia , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Canine models have many advantages for evaluating therapy of human central nervous system (CNS) diseases. In contrast to nonhuman primate models, naturally occurring canine CNS diseases are common. In contrast to murine models, the dog's lifespan is long, its brain is large and the diseases affecting it commonly have the same molecular, pathological and clinical phenotype as the human diseases. We compared the ability of four intracerebrally injected adeno-associated virus vector (AAV) serotypes to transduce the dog brain with green fluorescent protein as the first step in using these vectors to evaluate both delivery and efficacy in naturally occurring canine homologs of human diseases. Quantitative measures of transduction, maximum diameter and area, identified both AAV2/9 and AAV2/rh10 as significantly more efficient than either AAV2/1 or AAV2/5 at transducing cerebral cortex, caudate nucleus, thalamus and internal capsule. Fluorescence co-labeling with cell-type-specific antibodies demonstrated that AAV2/9 and AAV2/rh10 were capable of primarily transducing neurons, although glial transduction was also identified and found to be more efficient with the AAV2/9 vector. These data are a prerequisite to evaluating the efficacy of recombinant AAV vectors carrying disease-modifying transgenes to treat naturally occurring canine models in preclinical studies of human CNS disease therapy.
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Encéfalo/metabolismo , Dependovirus/genética , Vetores Genéticos , Transdução Genética , Animais , Encéfalo/virologia , Núcleo Caudado/metabolismo , Núcleo Caudado/virologia , Córtex Cerebral/metabolismo , Córtex Cerebral/virologia , Dependovirus/classificação , Dependovirus/fisiologia , Modelos Animais de Doenças , Cães , Proteínas de Fluorescência Verde/genética , Humanos , Cápsula Interna/metabolismo , Cápsula Interna/virologia , Sorotipagem , Tálamo/metabolismo , Tálamo/virologia , TransgenesRESUMO
This report summarizes recommendations relating to haemophilia therapy arising from discussions among experts from 36 European countries during the Kreuth III meeting in April 2013. To optimize the organization of haemophilia care nationally, it is recommended that a formal body be established in each country to include the relevant clinicians, national haemophilia patient organization, health ministry, paying authority and (if appropriate) regulatory authorities. The minimum factor VIII consumption level in a country should be 3 I.U. per capita. Decisions on whether to adopt a new product should not be based solely on cost. Prophylaxis for children with severe haemophilia is already recognized as the optimum therapy. Ongoing prophylaxis for individual adults should also be provided when required based on clinical decision making by the clinician in consultation with the patient. Children with inhibitors who have failed, or who are not suitable for, immune tolerance therapy should be offered prophylaxis with bypassing agents. Single factor concentrates should be used as therapy wherever possible in patients with rare bleeding disorders. Orphan drug designation for a factor concentrate should not be used to hinder the development, licencing and marketing of other products for the same condition which have demonstrably different protein modification or enhancement.
Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Hemofilia A/tratamento farmacológico , Criança , Consenso , Europa (Continente) , Humanos , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND AND PURPOSE: Since early treatment of acute stroke is associated with an improved outcome, emergency medical service (EMS) transport of stroke patients is recommended. It remains unclear, however, whether EMS transport leads to faster treatment. The impact of the transport mode on pre- and in-hospital processes of care was therefore investigated. METHODS: The present study was based on a prospective database of 158 hospitals of the Stroke Register of Northwestern Germany, which included 162,511 stroke patients admitted between January 2010 and December 2011. Main outcome measures were the baseline characteristics associated with EMS transport and process-of-care indicators according to the transport mode. RESULTS: Overall, 101,850 (72.0%) patients were transported by EMS and 39,324 (28.0%) by self-transport. The baseline characteristics showing the strongest associations with EMS use were the care situation [institutional care, adjusted odds ratio (OR) 7.81; 95% CI 6.86-8.90], a disturbed level of consciousness (adjusted OR 3.00; 95% CI 2.59-3.48) and having a subarachnoid (adjusted OR 2.79; 95% CI 2.24-3.49) or intracerebral hemorrhage (adjusted OR 2.26; 95% CI 1.92-2.67). For self-transport patients the probability of being in a higher onset-to-door time category was 4.36 (95% CI 4.26-4.47) and the probability of being in a higher door-to-imaging time category was 1.32 (95% CI 1.28-1.36). Compared with self-transport, EMS transport was independently associated with thrombolysis (adjusted OR 1.95, 95% CI 1.77-2.15). CONCLUSIONS: Patient transport with EMS was independently associated with faster hospital arrival and shorter time periods from hospital admission to brain imaging and to the frequency of thrombolysis.
Assuntos
Admissão do Paciente/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Acidente Vascular Cerebral/terapia , Transporte de Pacientes/estatística & dados numéricos , Idoso , Feminino , Alemanha , Humanos , Masculino , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: B-type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP-associated risk results from coronary atherosclerosis or atrial fibrillation. METHODS: Three thousand six hundred and seventy five subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.6% men) without previous stroke, coronary heart disease, myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators were followed up over 110.1 ± 23.1 months. Cox proportional hazards regressions were used to examine BNP as a stroke predictor in addition to vascular risk factors (age, gender, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes, smoking), renal insufficiency, atrial fibrillation/known heart failure and coronary artery calcification. RESULTS: Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects suffering stroke had significantly higher BNP values at baseline than the remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001]. In a multivariable regression, log10 BNP was an independent stroke predictor [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24-3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P = 0.037) and computed-tomography-based log10 (coronary artery calcification + 1) (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women, both in subjects ≤65 and >65 years. In subsequent analyses, BNP discriminated the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367) origin. CONCLUSIONS: BNP predicts presumable cardioembolic stroke independent of coronary calcification.
Assuntos
Calcinose/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Acidente Vascular Cerebral/diagnóstico , Fatores Etários , Idoso , Biomarcadores/sangue , Calcinose/sangue , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologiaRESUMO
OBJECTIVES: In aging populations, the prevalence of neurological disorders increases, which imposes high population burden in terms of mortality, disability, and impaired quality of life. The aim of this study was to assess the prevalence of common neurological disorders and signs and their association with functioning and mortality in an elderly general population. MATERIALS AND METHODS: We used data from the Memory and Morbidity in Augsburg Elderly (MEMO) project, a population-based study of 385 individuals aged ≥65. The prevalence of neurological disorders and signs was assessed by physical examination and medical interview. The basic and instrumental activities of daily living were assessed (ADL, IADL). We assessed the association of neurological disorders and signs with everyday functioning and prospectively analyzed their relationship with mortality. RESULTS: We observed considerably impaired functioning for cases with stroke, TIA, PD, and mild motor parkinsonian signs (MMPS). All-cause mortality was significantly increased in participants with stroke and MMPS, even after adjusting for co-variables (HR = 2.71 and 1.80, respectively). CONCLUSIONS: We found that not only specific neurological disorders, but also earlier symptoms are related to impaired functioning and predict mortality in the elderly. These findings have potential clinical relevance for screening and early detection of individuals at risk.