A conceptual disease model for adult Pompe disease

__Background:__ Studies in orphan diseases are, by nature, confronted with small patient populations, meaning that randomized controlled trials will have limited statistical power. In order to estimate the effectiveness of treatments in orphan diseases and extrapolate effects into the future, alternative models might be needed. The purpose of this study is to develop a conceptual disease model for Pompe disease in adults (an orphan disease). This conceptual model describes the associations between the most important levels of health concepts for Pompe disease in adults, from biological parameters via physiological parameters, symptoms and functional indicators to health perceptions and final health outcomes as measured in terms of health-related quality of life. __Methods:__ The structure of the Wilson-Cleary health outcomes model was used as a blueprint, and filled with clinically relevant aspects for Pompe disease based on literature and expert opinion. Multiple observations per patient from a Dutch cohort study in untreated patients were used to quantify the relationships between the different levels of health concepts in the model by means of regression analyses. __Results:__ Enzyme activity, muscle strength, respiratory function, fatigue, level of handicap, general health perceptions, mental and physical component scales and utility described the different levels of health concepts in the

Differences in the Experience of Caregiving Between Spouse and Adult Child Caregivers in Dementia With Lewy Bodies.

Background and objectivesDementia caregiving has been associated with increased burden, depression, grief, a decreased sense of well-being and quality of life, and a weakening of social support. Little is known about the experience of caregiving in Dementia with Lewy Bodies (DLB). The present study examines differences in the caregiving experience of spouse versus adult child caregivers of individuals with DLB.Research design and methodsIn this cross-sectional analytic study of spouses (n = 255) and adult children (n = 160) caregivers of individuals with DLB, participants completed an online survey of burden, grief, depression, well-being, quality of life, and social support.ResultsAdult child caregivers were more likely to care for women (p < .001) and see the care recipient less often (p < .001) than spouses. Adult child caregivers reported lower quality of life (p < .001) and more caregiver burden (p < .009), but also greater social support (p < .001) than spouses. Between group analyses of caregiver type by disease severity demonstrated that spousal caregivers experience greater grief with advancing disease (p = .005), while adult child caregivers increase social support with advancing disease (p < .001).Discussion and implicationsSpouses and adult children experience DLB caregiving differently. This was explained by the younger age of the adult child caregiver, frequency of contact with the care recipient, and differences in the care recipient's characteristics, frequency of neuropsychiatric symptoms, and disease severity. DLB caregiver support for this population should target psychoeducation for complicated neuropsychiatric symptoms in the care recipient. Screening all DLB caregivers for burden, grief, and depression is suggested to identify those that may benefit most from intervention. Spouses specifically may benefit from interventions that target increasing social support, while adult child caregivers may benefit from interventions aimed at mitigating burden and improving quality of life

Disease course, frequency of relapses and survival of 73 patients with juvenile or adult dermatomyositis

Objective Our aim is to present the disease course, frequency of relapses and survival of juvenile and adult dermatomyositis (JDM/DM) patients. Methods Analysis was performed using data on 73 patients. The median follow-up for 38 JDM patients was 32 months and 78 months for 35 adult DM patients. Results 23/38 JDM patients (60%) had monophasic, 12/38 (31.6%) had polycyclic and 3138 (7.9%) had chronic disease. Among children treated only with glucocorticoids, 12/20 (60%) had monophasic and 8/20 (40%) had polycyclic disease. 10/17 (58.8%) children, who required second-line immunosuppressive agents, had monophasic and 4/17 (23.5%) had polycyclic disease. 18/35 DM (51.4%) patients had monophasic, 13/35 (37.1%) had polycyclic, 1/35 (2.9%) had chronic disease and 3135 (8.6%) had fulminant myositis. Among DM patients requiring only glucocorticoids, 12/20 (60%) were monophasic and 8/20 (40%) were polycyclic. In patients requiring second-line immunosuppressive agents, 6/15 patients (40%) had monophasic and 5/15 (33.3%) had polycyclic disease. Among patients with polycyclic disease, the risk of relapse was higher during first year than later in the disease course. None of the JDM patients have died, while 4 disease-specific deaths occurred in adult patients. There was no significant difference between the survival of JDM and DM patients. Discussion There was no correlation between relapse-free survival and the initial therapeutic regimen. Many of our patients had polycyclic or chronic disease. As relapses can occur after a prolonged disease-free interval, patients should be followed for at least 2 years. Although we found a favourable survival rate, further investigations are needed to assess functional outcome

Temporal discrimination: Mechanisms and relevance to adult-onset dystonia

Temporal discrimination is the ability to determine that two sequential sensory stimuli are separated in time. For any individual, the temporal discrimination threshold (TDT) is the minimum interval at which paired sequential stimuli are perceived as being asynchronous; this can be assessed, with high test-retest and inter-rater reliability, using a simple psychophysical test. Temporal discrimination is disordered in a number of basal ganglia diseases including adult-onset dystonia, of which the two most common phenotypes are cervical dystonia and blepharospasm. The causes of adult-onset focal dystonia are unknown; genetic, epigenetic, and environmental factors are relevant. Abnormal TDTs in adult-onset dystonia are associated with structural and neurophysiological changes considered to reflect defective inhibitory interneuronal processing within a network which includes the superior colliculus, basal ganglia, and primary somatosensory cortex. It is hypothesized that abnormal temporal discrimination is a mediational endophenotype and, when present in unaffected relatives of patients with adult-onset dystonia, indicates non-manifesting gene carriage. Using the mediational endophenotype concept, etiological factors in adult-onset dystonia may be examined including (i) the role of environmental exposures in disease penetrance and expression; (ii) sexual dimorphism in sex ratios at age of onset; (iii) the pathogenesis of non-motor symptoms of adult-onset dystonia; and (iv) subcortical mechanisms in disease pathogenesis

Brain imaging in Kufs disease type B. case reports

The clinical traits of Kufs disease (KD) type B (CLN13), an adult-onset neuronal ceroid lipofuscinosis (NCL), are well established according to the neurological features of the cases reported with mutations in CTSF. The neuroradiological characteristics of this uncommon disease have not yet been outlined

Intergenerational Transmission of Healthy Eating Behaviour and the Role of Household Income

This paper investigates the possibility of intergenerational transmission of unhealthy eating habits from parents to adult children. It uses the 2003 Scottish Health Survey and estimates the association between the present healthy eating behaviour of adult children and the past parental death from cardiovascular disease (CVD). It uses parental CVD death as an adverse health signal which may cause a healthy eating compensatory response in adult children. This response is due to increased chances and perception of genetic predisposition of adult children as well as an indicator for parental past unhealthy eating habits which may have been passed onto the adult children. Regression analysis suggests that paternal history has no impact on either sons or daughters, and maternal history influences negatively the eating behaviour of daughters only. Unhealthy eating intergenerational transmission appears to be more intense amongst lower household income individuals.intergenerational transmission, healthy eating, household income, cardiovascular disease, public health, gender

Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population

Associations of Blood Pressure and Cholesterol Levels During Young Adulthood With Later Cardiovascular Events.

BackgroundBlood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified.ObjectiveThe authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures.MethodsThe authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke.ResultsA total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ≥130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ≥80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk.ConclusionsCumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures

Living with phenylketonuria in adulthood: the PKU ATTITUDE study

Dietary treatment is the cornerstone of therapy for phenylketonuria (PKU), but adherence to low- phenylalanine diet progressively decreases after adolescence. We designed a survey to characterize the dietary habits of Italian adult PKU patients and to identify psychological factors influencing disease perception and adherence to diet. Participants to the survey (n = 111; response rate 94%) were asked to complete a structured questionnaire. Patients appeared to have an altered perception and awareness of the disease. About 40% of them did not consider PKU a disease and, despite declaring regular monitoring of phenylalanine levels (85%), nearly half of them reported a high plasma value over the last 6 months (>600 μmol/L, 48%) or were unable to specify it (31%). Adherence to PKU diet was unsatisfactory, with increased consumption of natural protein sources and reduced daily use of amino-acid supplements (<4–5 times/day in 82% patients). In addition to the intrinsic characteristics of AA formula (palatability, ease of use), the most important factor influencing their consumption was the increased social pressure associated with their use (55%). Plasma phenylalanine periodical measurements (61%) and examinations at metabolic centers (49%) were considered relevant for compliance to diet. In Italian adult PKU patients dietary management was found to be inadequate, likely due to inappropriate perception and knowledge of the disease, and lack of awareness of the negative impact of poor metabolic control in adult life. Clinicians should consider implementing more intense and tailored educational measures, as well as structured transitional care processes

Causes of adult deaths in developing countries : a review of data and methods

Relatively little attention has been paid to the problem of premature adult mortality in developing countries, despite high levels of mortality in many countries - and despite the potentially severe social and economic consequences of adult deaths. Circulatory diseases and external causes appear to be major causes of adult deathsin most countries. The relative contribution of other important causes - including tuberculosis, cancer, liver disease, respiratory disease, and maternity related complications varies between countries. Techniques for determining cause specific adult mortality require thorough field testing and validation. The authors discuss several possible approaches, and categorize selected major causes of death according to whether they are likely to be diagnosed or excluded, on the basis of symptoms reported by relatives. They consider methods for classifying and presenting data on cause of death and conclude with recommendations for further methodological research.Demographics,Health Monitoring&Evaluation,Health Systems Development&Reform,Health Indicators,Statistical&Mathematical Sciences