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BACKGROUND AND PURPOSE: Data suggest a relationship between sexual dysfunction, mainly erectile dysfunction in men, and worse disease progression in Parkinson's disease (PD). There is scant evidence on the correlates of sexual activity in PD patients. By involving a subgroup of 355 patients from the PRIAMO (Parkinson Disease Non Motor Symptoms) study, the present 24-month longitudinal prospective analysis aims to demonstrate that the presence of active sexual life is associated with disease progression in early PD. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models showed that gastrointestinal symptoms [odds ratio 0.56, 95% confidence interval (CI) 0.39-0.82, P = 0.003] and apathy (odds ratio 0.42, 95% CI 0.29-0.63, P < 0.001) were less likely to be associated with sexual activity in men. Analysis also demonstrated that sexual activity in men was associated with lower motor disability (coefficient -2.881, 95% CI -4.732 to -1.030, P = 0.002), better quality of life (coefficient -24.196, 95% CI -44.884 to -3.508, P = 0.022; coefficient 0.083, 95% CI 0.023-0.143, P = 0.006) and lower depression scores (coefficient -1.245, 95% CI -2.104 to -0.387, P = 0.004). No association was shown in women. CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients suggesting that sexual activity is associated with lower motor and non-motor disability as well as with better quality of life in men. These findings should prompt movement disorders specialists to periodically inquiry about their patients' sexual life.
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Transtornos dos Movimentos/etiologia , Doença de Parkinson/psicologia , Comportamento Sexual/psicologia , Adulto , Idade de Início , Idoso , Apatia , Estudos de Coortes , Avaliação da Deficiência , Progressão da Doença , Feminino , Gastroenteropatias/etiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Estudos Prospectivos , Qualidade de Vida , Caracteres Sexuais , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: New venues are currently being explored to predict disease progression in Parkinson's disease (PD), such as non-motor subtypes and models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585 patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the present 24-month longitudinal prospective analysis aimed to demonstrate that urinary dysfunction is an early marker of higher motor and non-motor burden as well as lower health-related quality of life. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models controlling for demographic and clinical variables showed that the following NMS domains were associated with urinary dysfunction: gastrointestinal [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.67-3.97, P < 0.001], cardiovascular (OR 2.22, 95% CI 1.18-4.17, P = 0.013), skin (OR 1.81, 95% CI 1.06-3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34-3.16, P = 0.001), pain (OR 1.85, 95% CI 1.21-2.83, P = 0.004), fatigue (OR 2.40, 95% CI 1.56-3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72-4.52, P < 0.001) and respiratory (OR 1.82, 95% CI 1.02-3.23, P = 0.039). Analysis also demonstrated that urinary dysfunction was associated with higher motor disability (coefficient 1.73, 95% CI 0.68-2.78, P = 0.001) and lower health-related quality of life (coefficient -0.05, 95% CI -0.08 to -0.02, P < 0.001, and coefficient -3.49, 95% CI -5.21 to -1.77, P < 0.001) but not with more severe cognitive disability (coefficient -0.34, 95% CI -0.92 to 0.24, P = 0.251). CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients demonstrating the relevance of urinary dysfunction as an early marker of higher motor and non-motor disability as well as lower health-related quality of life. These findings support a role for urinary dysfunction as an early marker of more severe disease progression.
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Progressão da Doença , Fadiga/complicações , Doença de Parkinson/complicações , Qualidade de Vida , Transtornos Urinários/complicações , Idoso , Apatia/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Sono/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Grey matter (GM) and white matter (WM) are both affected in multiple sclerosis (MS). WM is predominantly involved in inflammatory demyelination of relapsing-remitting MS (RRMS), whereas GM is predominantly involved in neurodegenerative processes of secondary progressive MS. Thus, we investigated the ratio between GM and WM volumes in predicting MS evolution. METHODS: The present 10-year retrospective cohort study included 149 patients with newly-diagnosed RRMS, undergoing magnetic resonance imaging for segmentation and brain volumetry. The ratio between GM and normal-appearing WM (NAWM) volumes was calculated for each subject. Outcome measures of interest were Expanded Disability Status Scale (EDSS) progression, reaching EDSS 4.0 and conversion to secondary progressive (SP) MS. RESULTS: During a period of 10.6 ± 2.4 years, a median 1.5 EDSS progression was observed (range 0-5.5), 54 subjects (36.2%) reached EDSS 4.0 and 30 subjects (20.1%) converted to SP. With ordinal logistic regression models, EDSS progression was associated with GM:NAWM ratio (coefficient, -2.918; 95% CI, -4.739-1.097). With Cox regression models, subjects with higher GM:NAWM ratio at diagnosis had a 90% lower rate of reaching EDSS 4.0 (hazard ratio, 0.111; 95% CI, 0.020-0.609) and of converting to secondary progressive MS (hazard ratio, 0.017; 95% CI, 0.001-0.203) compared with subjects with lower GM:NAWM ratio. CONCLUSIONS: The GM:NAWM ratio is a predictor of disability progression and of SP conversion in subjects with newly diagnosed RRMS, suggesting that GM and NAWM are variably affected in relation to disease evolution from the early phases of MS.
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Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES: Disease-modifying treatments (DMTs) constitute the largest direct medical cost for multiple sclerosis (MS). This study aims at investigating predictors of the 10-year economic burden for DMT administration and management. MATERIALS AND METHODS: This study included 537 newly diagnosed, drug naïve relapsing-remitting MS (RRMS) patients, followed up for 10.1±3.3 years. Costs for DMT administration and management were calculated, and referred to each year of observation (annual costs). Possible predictors of disease evolution were categorized into early predictors (age, gender, disease duration, baseline expanded disability status scale (EDSS), 1-point EDSS progression within 2 years, and annualized relapse rate -ARR- within 2 years), and long-term predictors (reaching of EDSS 4.0, conversion to secondary progressive -SP-, ARR, number of DMTs, follow-up duration). Association between predictors and study outcome was explored using mixed-effects log-linear regression models. RESULTS: A 1-point higher EDSS at diagnosis was associated with 13.21% increase in the annual costs (95%CI=4.16-23.04%). Each additional year of age at diagnosis was associated with a 0.74% decrease in the annual costs (95%CI=-1.43 to-0.04%). Female gender was associated with a 12.43% decrease in the annual costs (95%CI=-22.61 to-0.93%). Converting to SP was associated with a 14.26% decrease in the annual costs (95%CI=-14.26 to-2.94%). Each additional year of follow-up was associated with a 3.05% decrease in the annual costs (95%CI=-4.51 to-1.57%). CONCLUSIONS: An estimate of the 10-year costs associated with DMT administration and management can be calculated by analyzing different factors, and might be of particular interest for planning resources needed for treating people with MS.
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Progressão da Doença , Custos de Cuidados de Saúde/tendências , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/economia , Adulto , Estudos de Coortes , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Uric acid (UA) has been studied extensively as a valuable biomarker of Parkinson's disease (PD), but its relationship with non-motor symptoms (NMS) in de novo PD has been poorly investigated. Our aim was to evaluate the usefulness of baseline serum UA as a marker of NMS progression in newly diagnosed PD. METHODS: Sixty-nine newly diagnosed PD patients were enrolled. At baseline, all patients completed the NMS questionnaire (NMSQuest), and serum UA levels were measured. After 2 years, the NMSQuest was completed again and patients were categorized into four groups: NMS improvement (domain involvement at baseline but not at 2-year follow-up visit), NMS absence (domain not involved at baseline or 2-year follow-up visits), NMS presence (domain involvement both at baseline and 2-year follow-up visits) and NMS worsening (domain not involved at baseline but involved at 2-year follow-up). RESULTS: ANOVA with post hoc Bonferroni correction showed that patients with NMS absence presented significantly higher UA values than patients with NMS presence with regard to the attention/memory (P = 0.023), depression/anxiety (P = 0.028) and cardiovascular domains (P = 0.002), whilst no differences were found with regard to both the NMS improvement and worsening groups. In addition, multinomial regression analysis showed that the lowest tertile of NMS progression presented higher UA levels (P = 0.023; odds ratio 0.488) compared with patients with greater NMS progression. CONCLUSIONS: This is the first report of a relationship between serum UA and presence/progression of multiple NMS in de novo PD, providing additional evidence of the reliability of UA as a biomarker of PD and opening new insights on PD neuroprotection.
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Progressão da Doença , Doença de Parkinson/fisiopatologia , Ácido Úrico/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/classificaçãoRESUMO
BACKGROUND AND PURPOSE: Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10-year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS-related outcomes. METHODS: Age, gender, smoking status, body mass index, systolic blood pressure, type II diabetes and use of antihypertensive medications were recorded in subjects with and without MS to estimate the FR, an individualized percentage risk score estimating the 10-year likelihood of cardiovascular events. RESULTS: In total, 265 MS subjects were identified with 530 matched controls. A t test showed similar FR in cases and controls (P = 0.212). Secondary progressive MS presented significantly higher FR compared to relapsing-remitting MS (P < 0.001). Linear regression analysis showed a direct relationship between FR and Expanded Disability Status Scale (P < 0.001) and MS Severity Scale (P < 0.001). CONCLUSION: The FR, evaluating the global cardiovascular health by the interaction amongst different risk factors, relates to MS disability, severity and course.
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Doenças Cardiovasculares/epidemiologia , Esclerose Múltipla Crônica Progressiva/epidemiologia , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Risco , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Oxidative stress is a central pathogenic mechanism of Parkinson's disease (PD), and the heme oxygenase (HO) bilirubin pathway is one of the main mammalian antioxidative defences. Indeed, there is growing evidence of HO-bilirubin upregulation from early phases of PD. Our aim was to investigate bilirubin as a possible biomarker of PD diagnosis and progression. METHODS: A cross-sectional case-control study was performed to evaluate differences in bilirubin levels between newly diagnosed, drug-naïve PD subjects and controls. Afterwards, PD subjects were included in a 2-year longitudinal study to evaluate disease progression in relation to baseline bilirubin levels. RESULTS: Seventy-five de novo PD subjects were selected and matched with 75 controls by propensity score. Analysis of variance showed higher bilirubin levels in PD patients compared with controls (P < 0.001). Linear regression analysis failed to show a relationship between bilirubin and Unified Parkinson's Disease Rating Scale (UPDRS) part III (P = 0.283) at baseline evaluation. At 2-year follow-up, indirect relationships between bilirubin levels and UPDRS part III (P = 0.028) and between bilirubin levels and levodopa-equivalent daily dosage (P = 0.012) were found. CONCLUSIONS: Parkinson's disease subjects showed higher levels of bilirubin compared with controls. Bilirubin increase might be due to HO overexpression as a compensatory response to oxidative stress occurring from early stages of PD.
Assuntos
Bilirrubina/sangue , Doença de Parkinson/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Diagnosing Parkinson's disease (PD) and tracking its progression may require the combination of reliable biomarkers. Among them, both serum uric acid (UA) and dopamine transporter (DaT) binding deserve more investigations. AIMS OF THE STUDY: We aimed to investigate the relationship between serum UA levels and DaT availability in newly diagnosed, drug-naïve PD patients, by means of semiquantitative [(123) I]FP-CIT-SPECT. METHODS: We recruited 52 newly diagnosed, drug-naïve PD patients, and performed serum UA dosage and [(123) I]FP-CIT-SPECT. RESULTS: Pearson's correlation analysis showed that UA levels were significantly higher in patients with higher averaged, ipsilateral and contralateral DaT binding in caudate, putamen, and striatum. CONCLUSIONS: We showed, for the first time, by regional semiquantitative analysis of DaT binding in PD patients that UA levels significantly correlates with the severity of dopaminergic impairment in caudate, putamen, and striatum. This study broadens our knowledge on the importance of UA as a biomarker of PD.
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Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico por imagem , Ácido Úrico/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteínas da Membrana Plasmática de Transporte de Dopamina/análise , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , TropanosRESUMO
BACKGROUND: The care-associated infections (HAI) are the most serious complication associated with medical care. They are the cause of diseases for patients and economic damage to public health. The University "Federico II" of Naples decided to monitor the HAI, repeating the prevalence survey conducted earlier in 2011 in order to analyze the phenomenon of infection and to evaluate the possible correlation with risk factors. METHODS: The Survey was conducted according to ECDC criteria. Considered that the study carried out in 2011 was conducted following the same methodology, to compare the results of the year 2012 the prevalence rates of both years were standardized. FINDINGS: For the year 2012, the number of patients enrolled in the study and stratification of patients by age and sex were similar to data collected in 2011. It was very interesting to find the prevalence of HAI standardized reduced in 2012 compared to 2011. As a matter of fact, in fact, that the standardized prevalence of HAI for the year 2012 was 3.1%, one percentage point lower than in 2011 (4.4%). CONCLUSIONS: The practical training and direct regarded as the most appropriate approach in order to make health professionals aware in the field of health care-associated infections, as well as the system of selfcontrol peripheral for the correct application of the procedures, as well as epidemiological surveillance active, measured through rates of incidence, at the same time allow the monitoring of the phenomenon is infectious and the application of corrective measures that prevent its onset. The choice to make again an epidemiological study of prevalence with the same methodology ensures, in fact, two advantages: the comparability of the data, both at intra-company both at regional, national and international evaluation of the effectiveness of corrective actions.
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Infecção Hospitalar/epidemiologia , Pessoal de Saúde/normas , Controle de Infecções/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Infecção Hospitalar/prevenção & controle , Coleta de Dados , Feminino , Pessoal de Saúde/educação , Hospitais Universitários , Humanos , Incidência , Lactente , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Peginterferon ß-1a (PEG-IFN-ß-1a) is the most recent interferon beta formulation approved for treating relapsing-remitting multiple sclerosis (RRMS). We aim to describe the real-world utilization of PEG-IFN-ß-1a in RRMS and compare it with other injectable disease-modifying therapies (DMTs). PATIENTS AND METHODS: In this population-based study, we used 2015-2019 routinely collected healthcare data of the Campania region of Italy from National Healthcare System DMT prescriptions, inpatient and outpatient clinical records of hospitals in Campania, and the Federico II University MS clinical registry for a subset of patients. We included individuals with RRMS receiving new prescriptions of PEG-IFN-ß-1a [n=281; age = 38.8±12.3 years; females=70.5%; disease duration = 8.4±8.3 years; Expanded Disability Status Scale (EDSS) at baseline=2.0 (1.0-6.5)], glatiramer acetate [n=751; age = 46.0±11.4 years; females=67.1%; disease duration = 9.8±8.2 years; EDSS=4.0 (1.5-8.5)], and subcutaneous (SC) IFN-ß-1a [n=1,226; age = 39.7±11.7 years; females=66.5%; disease duration = 8.2±6.5 years; EDSS 2.5 (1.5-6.5)]. Adherence [medication possession ratio (MPR)], escalation to more effective DMTs, hospitalization rates and costs were measured. We used mixed-effect linear regression models (for adherence, hospitalization rates and costs) and Cox regression models (for escalation) to assess differences between PEG-IFN-ß-1a (statistical reference), glatiramer acetate, and SC IFN-ß-1a. All models included age, sex, previous treatment/untreated, year of treatment initiation, treatment duration, and adherence as covariates. RESULTS: Adherence was lower in glatiramer acetate (MPR = 0.91±0.1; Coeff=-0.11; p<0.01), and IFN-ß-1a (MPR = 0.92±0.1; Coeff=-0.08; p<0.01), compared with PEG-IFN-ß-1a (MPR = 1.01±0.1). The probability of escalating to more effective DMTs was higher for glatiramer acetate (14.9%; HR=4.09; p<0.01) and IFN-ß-1a (9.1%; HR=3.35; p=0.01), compared with PEG-IFN-ß-1a (4.9%). No differences in annualized hospitalization rates were identified between glatiramer acetate [annualized hospitalization rates (AHR) = 0.05±0.30; Coeff=0.02; p=0.31), IFN-ß-1a (AHR = 0.02±0.21; Coeff=0.01; p=0.97], and PEG-IFN-ß-1a (AHR = 0.02±0.24); however, monthly costs for MS admissions were higher for glatiramer acetate (49.45±195.27; Coeff=-29.89; p=0.03), compared with IFN-ß-1a (29.42±47.83; Coeff=6.79; p=0.61), and PEG-IFN-ß-1a (23.91±43.90). CONCLUSIONS: SC PEG-IFN-ß-1a and IFN-ß-1a were used in relatively similar populations, while glatiramer acetate was preferred in older and more disabled patients. PEG-IFN-ß-1a was associated with higher adherence and lower escalation rates toward more effective (and costly) DMTs.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Polietilenoglicóis , Feminino , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Acetato de Glatiramer/uso terapêutico , Interferon beta-1a/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Interferon beta/uso terapêuticoRESUMO
Correction to: European Review for Medical and Pharmacological Sciences 2024; 28 (1): 411-418. DOI: 10.26355/eurrev_202401_34930-published online on January 16, 2024. After publication, the authors have applied some corrections to the galley proof: ⢠In the Patients and Methods section of the abstract, "National Health System" is corrected to "National Health Service". ⢠In the Conclusions section of the abstract, "SC PEG-IFN-ß-1a and IFN- ß-1a" is corrected to "PEG-IFN-ß-1a and SC IFN-ß-1a". ⢠In the Population section, the study period "January 1st 2015 to December 31st 2019" was not reported; therefore, this specification has been added to the text. ⢠The legend of Figure 1 was wrongly reported as the same as Table I. The correct title of Figure 1 is "Study flow diagram". ⢠Under Tables I, II, and III, "interferon beta 1a IFN-ß-1a" is corrected to "interferon beta 1a (IFN-ß-1a)". ⢠In Table III, "CS Glatiramer acetate" is corrected to "SC Glatiramer acetate". ⢠In the Conclusions section, "SC IFN-ß-1a SC" is corrected to "SC IFN-ß-1a". ⢠The funding section has been amended as follows: "This study was sponsored by Biogen Italia (Milan, Italy)." There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34930.
RESUMO
BACKGROUND: Healthcare Associated Infections (HAI) are the most serious complication associated with health care. They cause diseases for patients and economic damage for Public Health. A prevalence survey at the University Hospital "Federico II" of Naples was conducted according to ECDC criteria in order to analyze the infectious phenomenon of healthcare assistance and assess possible correlations with risk factors as healthcare procedure and clinical condition of patients. METHODS: Were enrolled 450 patients. The collected data were then analyzed using univariate and multivariable logistic regression. RESULTS: It was found a prevalence rate of infections of 9.3%, with a prevalence rate of HAI of 4.4%. Statistical analysis showed correlation between HAI and ultimately-fatal-disease (P <0.04) and between HAI and the use of invasive devices as CVC (P<0.005), PVC (P<0.004) and intubation (P<0.01). CONCLUSIONS: The epidemiological surveillance strategies are part of preventive measures and monitoring of the HAI, implemented to ensure safety and quality of care.
Assuntos
Infecção Hospitalar/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Coleta de Dados , Feminino , Hospitais Universitários , Humanos , Lactente , Itália , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
The objective of this study was to investigate the effect of 2 breeds, Holstein and Jersey, and their F(1) hybrid (Jersey x Holstein) on milk fatty acid (FA) concentrations under grazing conditions, especially conjugated linoleic acid (CLA) and n-3 polyunsaturated fatty acids because of their importance to human health. Eighty-one cows (27 per breed grouping) were allocated a predominantly perennial ryegrass pasture. Samples were collected over 2 periods (June and July). Breed affected dry matter intake and milk production and composition. Holstein cows had the highest dry matter intake (18.4+/-0.40kg of DM/d) and milk production (21.1+/-0.53kg of DM/d). Holstein and Jersey x Holstein cows had similar 4% fat corrected milk, fat yield, and protein yield; with the exception of fat yield, these were all higher than for Jersey cows. Milk fat concentration was highest for Jersey cows and lowest for Holstein cows, with the hybrid cows intermediate. Total FA and linolenic acid intake (1.09+/-0.023 and 0.58+/-0.012 kg/d, respectively) were highest for Holstein cows. In terms of milk FA, Holstein cows had higher contents of C14:1, cis-9 C18:1 and linoleic acid. In turn, Jersey and Jersey x Holstein cows had higher content of C16:0. Milk concentrations of neither the cis-9,trans-11 isomer of CLA nor its precursor, vaccenic acid, were affected by breed. Nevertheless, large variation between individual animals within breed grouping was observed for CLA and estimated Delta(9)-desaturase activity. There was some evidence for a negative heterotic effect on milk concentration of CLA, with the F(1) hybrid cows having lower concentrations compared with the mid parent average. Plasma FA profile did not accurately reflect differences in milk FA composition. In conclusion, there was little evidence for either breed or beneficial heterotic effects on milk FA content with human health-promoting potential, though significant within-breed, interanimal variation was observed.
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Bovinos/genética , Bovinos/metabolismo , Indústria de Laticínios/métodos , Ácidos Graxos/análise , Hibridização Genética/fisiologia , Leite/química , Animais , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Feminino , Lactação , Masculino , Leite/metabolismo , Especificidade da EspécieRESUMO
BACKGROUND: Dimethyl-fumarate (DMF) was effective and safe in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. We aimed to evaluate the efficacy and safety of DMF and factors related to drug response in real-life setting. METHODS: We analysed prospectively collected demographic and clinical data for patients treated with DMF in six multiple sclerosis (MS) centers from 2015 to 2017 in Campania region, Italy. We performed univariate and multivariate analyses to assess relationships between baseline parameters and DMF efficacy outcomes, Annualized Relapse Rate (ARR), Expanded Disability Status Scale (EDSS) progression and No Evidence of Disease Activity (NEDA-3) status. RESULTS: we analyzed data of 456 patients (67% female subjects, mean age 40 ± 12 years, mean disease duration 9 ± 9 years, mean treatment duration 18 ± 11 months, median EDSS 2.5, 0-8). Proportion of Naïve versus pretreated with other DMTs patients was 149/307 (32.7%), with 122 patients switching to DMF for disease activity (26.7%) and 185 for safety and tolerability issues (40.6%). During treatment with DMF, the annualized relapse rate was reduced by 75% respect to the pre-treatment ARR [incidence-rate-ratio (IRR) = 0.25, p < 0.001, CI 0.18-0.33]. Factors influencing ARR rate while on DMF were relapsing remitting (RR) MS course (IRR = 2.0, p = <0.001, CI 1.51-2.73) and previous DMTs status: de-escalating from second-line therapies was associated to higher risk of relapsing (IRR = 1.8, p < 0.001, CI 1.39-2.31). At multivariable Cox proportional hazard model, only age of onset was related with rate or relapses, with younger age being protective (HR 0.96, p = 0,02). EDSS remained stable in 88% of patients. Disease duration was associated with higher rate of NEDA-3 failure, that was instead maintained in 65% of patients at 24 months. 109 patients (22%) discontinued therapy after a mean of 1.1 ±+ 0.7 years. Reasons for DMF discontinuation over time were lack of efficacy (50%), safety issues (30%), tolerability (7%), poor compliance (7%), and pregnancy (4%). Higher pre-treatment EDSS was associated with DMF discontinuation (p = 0.009). Only 33 patients dropped out due to safety reasons (7%), the most frequent safety issues driving to drop out being lymphopenia, liver/pancreatic enzymes increase, gatrointestinal severe tolerability issues. We recorded 95 cases (24%) of lymphopenia: 60 grade I (13%), 31 grade II (7%) and 4 grade III (1%). CONCLUSIONS: We confirm that DMF shows a good efficacy in both naïve patients and patients switching from other first-line DMTs, especially in patients with early onset of disease. Higher baseline EDSS was a risk factor for discontinuing DMF therapy, while shorter disease duration was protective for both EDSS progression and NEDA-3 status maintenance.
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Fumarato de Dimetilo/farmacologia , Progressão da Doença , Fatores Imunológicos/farmacologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idade de Início , Fumarato de Dimetilo/efeitos adversos , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Fatores de TempoRESUMO
The objective of this study was to investigate the effect of level of 1) pregrazing herbage mass (HM) and 2) level of daily herbage allowance (DHA) on the performance and fatty acid (FA) composition of milk from grazing dairy cows. Sixty-eight Holstein-Friesian dairy cows were allocated to either a high or low pregrazing HM (1,700 vs. 2,400 kg of DM/ha; >40 mm), and within HM treatment, cows were further allocated to either a high or low DHA (16 vs. 20 kg of DM/d per cow; >40 mm) in a 2 x 2 factorial design. Pregrazing HM did not affect dry matter intake (17.5 +/- 0.75 kg/d), milk production (22.1 +/- 0.99 kg/d), milk composition (milk fat, 3.88 +/- 0.114%; milk protein, 3.28 +/- 0.051%), body weight (525 +/- 16 kg), or body condition score (2.65 +/- 0.064). Increasing DHA increased dry matter intake (+1.5 kg/d) but did not affect any other variable measured. Cows grazing the low HM or high DHA had a higher daily intake of total FA (+0.12 and +0.09 kg/d, respectively, for the low HM and high DHA), alpha-linolenic acid (LNA; +0.08 and +0.05 kg/d, respectively, for the low HM and high DHA), and linoleic acid (+0.01 for both the low HM and high DHA) compared with either the high HM or low DHA. Milk conjugated linoleic acid (cis-9, trans-11 isomer) was not affected by treatment (13.0 +/- 0.77 g/kg of total FA); however, large variation was recorded between individual animals (range from 5.9 to 20.6 g/kg of total FA). Milk concentrations of LNA were higher for animals offered the low HM (5.3 g/kg of total FA), but across treatments, milk concentrations of LNA were low (4.9 +/- 0.33 g/kg of total FA). The present study indicates that changes in HM and DHA do not have a great effect on the milk FA composition of grazing dairy cows. Further enhancement of the beneficial FA content in milk purely from changes in grazing strategy may be difficult when pasture quality is already high.