Subjects/methods: Twenty-four-hour dietary recall data of 12-24-month-old toddlers (n = 544) was used to estimate the intakes of α-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), linoleic acid (LA; 18:2n-6), and arachidonic acid (AA; 20:4n-6), as well as the major dietary sources of each. The results were compared with the expected intake for exclusively breastfed infants in the first 6 months of life and available dietary recommendations.
the first 20 hours epub 13
Sleep duration has been shown to be associated with individual chronic diseases but its association with multimorbidity, common in older adults, remains poorly understood. We examined whether sleep duration is associated with incidence of a first chronic disease, subsequent multimorbidity and mortality using data spanning 25 years.
Data were drawn from the prospective Whitehall II cohort study, established in 1985 on 10,308 persons employed in the London offices of the British civil service. Self-reported sleep duration was measured 6 times between 1985 and 2016, and data on sleep duration was extracted at age 50 (mean age (standard deviation) = 50.6 (2.6)), 60 (60.3 (2.2)), and 70 (69.2 (1.9)). Incidence of multimorbidity was defined as having 2 or more of 13 chronic diseases, follow-up up to March 2019. Cox regression, separate analyses at each age, was used to examine associations of sleep duration at age 50, 60, and 70 with incident multimorbidity. Multistate models were used to examine the association of sleep duration at age 50 with onset of a first chronic disease, progression to incident multimorbidity, and death. Analyses were adjusted for sociodemographic, behavioral, and health-related factors.
The first objective of the present study was to examine the association between sleep duration at 50, 60, and 70 years of age and incident multimorbidity, using repeat data on sleep duration and continuous assessment of chronic diseases spanning over 25 years. A second objective was to determine whether sleep duration at age 50 shapes the natural course of chronic disease, from a healthy state, to a first chronic disease, multimorbidity, and death using multistate models to examine the association of sleep duration at age 50 with transitions between each of these health states. In these analyses, the focus is on sleep duration at age 50 as chronic conditions are less prevalent and reverse causation bias that could arise from underlying conditions affecting sleep duration is less likely. In additional analyses, we examined the association of sleep duration with the onset of multimorbidity and death in the subgroup of participants with 1 chronic condition to examine whether sleep pattern after onset of chronic conditions is associated with adverse health outcomes [15]. Finally, in post hoc analysis, the association between sleep disturbance at age 60 and 70, where we had data on these measures, and risk of incident multimorbidity was examined.
Health behaviors included cigarette smoking (never smoker, ex-smoker, current smoker), alcohol consumption in the previous week (none, 1 to 14 units per week, >14 units per week), time spent in moderate and vigorous physical activity (hours per week), and frequency of fruit and vegetable consumption (less than daily, once a day, twice or more a day).
The association of sleep duration at age 50, 60, and 70 with incident multimorbidity was examined in separated models. The analyses were undertaken using Cox proportional-hazards regression with age as the timescale in participants free from multimorbidity at the measurement of sleep duration. Data were censored at date of multimorbidity diagnosis, death to account for competing risk [37], or March 31, 2019, whichever came first. In analysis of sleep duration at age 50, age at the beginning of the follow-up was the age at clinical assessment closest to 50 years from which the sleep duration measure and covariates were drawn. A similar approach was used in analyses of sleep duration at age 60 and 70. The proportional hazards assumption was verified using Schoenfeld residuals. Analyses were first unadjusted (age as timescale; Model 1), then adjusted for sociodemographic measures (Model 2), and finally additionally for behavioral and health-related factors (Model 3).
Among participants at age 50, free from the 13 chronic diseases considered here, multistate models were used (Fig 1) to determine the association of sleep duration at age 50 with transitions from: (1) a healthy state to a first chronic disease (any from the list of 13 diseases considered); (2) a healthy state to death (in those who remained free from any of the 13 diseases during follow-up); (3) a first chronic disease to multimorbidity; (4) a first chronic disease to death; and (5) multimorbidity to death, with follow-up starting at age 50. The advantage of multistate models is that they take into account the time spent within each health state to estimate probabilities of transitions between each state. For comparison, we also examined (post hoc analysis) the association between sleep duration at age 50 and risk of mortality in the same study sample (participants free from chronic disease at age 50) irrespective of incidence of chronic disease over the follow-up.
Transition A represents the transition from a healthy state at age 50 (free of the 13 chronic diseases considered) to a first chronic disease (any from the list of 13 diseases considered); Transition B represents the transition from a healthy state to death among those who remained free from any of the 13 diseases during follow-up; Transition C represents the transition from a first chronic disease to multimorbidity (occurrence of a second disease among those with 1 chronic disease); Transition D represents the transition from a first chronic disease to death among those who remained free from multimorbidity during the follow-up; and Transition E represents the transition from multimorbidity to death.
In additional analyses, we examined the association of sleep duration after onset of a first chronic disease with transitions to multimorbidity and death, again using a multistate model. The follow-up here started at the measure of first sleep duration following the onset of a first chronic disease. In sensitivity analysis, we used inverse probability weighting to account for missing data [22].
Accelerometer data and covariates were available on 3,920 participants who took part to the accelerometer sub-study at the 2012 wave. Of them, 3,368 participants (mean age (SD) = 68.9 (5.6), range = 60 to 83 years) were free of multimorbidity and were included in the analysis. During a mean follow-up of 6 years, 601 developed multimorbidity. The correlation between accelerometer- and questionnaire-assessed sleep duration was moderate (Pearson correlation = 0.41, p
In post hoc analysis, first we showed results from analyses using inverse probability weighting to account for missing data to be consistent with those in the main analysis (S6 Table). Second, analysis excluding 1 disease at a time from the definition of multimorbidity showed results to be robust to the list of chronic diseases used to define multimorbidity (S7 Table). Third, we examined trajectories of sleep duration. The Pearson correlation of sleep duration at age 50 with sleep duration at age 60 was 0.49 and with sleep duration at age 70 was 0.42 (p
This prospective study spanning over 20 years presents 3 key findings. One, short sleep duration was consistently associated with increased risk of multimorbidity, irrespective of sleep being measured in mid or late life. The analysis of transitions in health states showed short sleep to be associated with the onset of a first disease and subsequent multimorbidity but not disease prognosis, measured using mortality. Two, the results for long sleep duration were less robust as associations with multimorbidity were observed when sleep was measured at age 60 and 70 but not at 50 years. In the analyses of transitions in health states, we also found long sleep at age 50 not to be associated with disease progression although some of the transitions could not be examined due to a small number of cases. Three, the accelerometer-based measure of sleep duration, undertaken when the mean age of participants was 69 years (range 60 to 83), confirmed the shape of the association between sleep duration and multimorbidity in the main analysis with results matching those observed for self-reported sleep duration at ages 60 or 70. Taken together, these findings suggest an association between short sleep duration and development of multimorbidity.
In 2018, we wrote a paper on the drug treatment of Parkinson's disease. In this article, we obtained that the wearing off was observed in 77%, but the incidence of dyskinesia was 37.7% for the Parkinson?s disease patients from the onset of the disease 16-20 years. In this review article, we will discuss some of the newer treatments of Parkinson?s disease first, i.e., transplantation with induced pluripotent stem cell-derived cells, gene therapy, deep brain stimulation, levodopa/ carbidopa intrajejunal gel infusion, MRI-supported focused ultrasound, and IPX066. Then, we will discuss our opinion on the mechanism of wearing off and dyskinesia, and modifications of levodopa treatment after the wearing off sets in. 2ff7e9595c
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