Summary Background Fibrillar amyloid-β (Aβ) is thought to begin accumulating in the brain many years before the onset of clinical impairment in patients with Alzheimer's disease. By assessing the ...accumulation of Aβ in people at risk of genetic forms of Alzheimer's disease, we can identify how early preclinical changes start in individuals certain to develop dementia later in life. We sought to characterise the age-related accumulation of Aβ deposition in presenilin 1 (PSEN1) E280A mutation carriers across the spectrum of preclinical disease. Methods Between Aug 1 and Dec 6, 2011, members of the familial Alzheimer's disease Colombian kindred aged 18–60 years were recruited from the Alzheimer's Prevention Initiative's registry at the University of Antioquia, Medellín, Colombia. Cross-sectional assessment using florbetapir PET was done in symptomatic mutation carriers with mild cognitive impairment or mild dementia, asymptomatic carriers, and asymptomatic non-carriers. These assessments were done at the Banner Alzheimer's Institute in Phoenix, AZ, USA. A cortical grey matter mask consisting of six predefined regions.was used to measure mean cortical florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were used to characterise the cross-sectional accumulation of fibrillar Aβ deposition in carriers and non-carriers with regression analysis and to estimate the trajectories of fibrillar Aβ deposition. Findings We enrolled a cohort of 11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20 asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age matched non-carriers. Fibrillar Aβ began to accumulate in PSEN 1E280A mutation carriers at a mean age of 28·2 years (95% CI 27·3–33·4), about 16 years and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively.18 F florbetapir binding rose steeply over the next 9·4 years and plateaued at a mean age of 37·6 years (95% CI 35·3–40·2), about 6 and 11 years before the expected respective median ages at mild cognitive impairment and dementia onset. Prominent florbetapir binding was seen in the anterior and posterior cingulate, precuneus, and parietotemporal and frontal grey matter, as well as in the basal ganglia. Binding in the basal ganglia was not seen earlier or more prominently than in other regions. Interpretation These findings contribute to the understanding of preclinical familial Alzheimer's disease and help set the stage for assessment of amyloid-modifying treatments in the prevention of familial Alzheimer's disease. Funding Avid Radiopharmaceuticals, Banner Alzheimer's Foundation, Nomis Foundation, Anonymous Foundation, Forget Me Not Initiative, Colciencias, National Institute on Aging, and the State of Arizona.
To determine the efficacy of group cognitive-behavioral therapy (CBT) on adolescents with attention-deficit/hyperactivity disorder (ADHD) who were in pharmacological treatment but still had ...persistent symptoms.
We conducted a multicenter, randomized, rater-blinded, controlled trial between April 2012 and May 2014 in a cohort of 119 adolescents (15-21 years of age). Participants were randomly assigned to 12 manualized group CBT sessions (n = 45) or a waiting list control group (n = 44). Primary outcomes were assessed by a blinded evaluator (ADHD Rating Scale ADHD-RS, Clinical Global Impression Scale for Severity CGI-S, Global Assessment of Functioning GAF) before and after treatment, as well as by self-report and parent informant ratings.
Of the initial 119 participants enrolled, 89 completed treatment. A mixed-effects model analysis revealed that participants who were assigned to the group CBT sessions experienced significantly reduced ADHD symptoms compared to the control group (ADHD-RS Adolescent: -7.46, 95% CI = -9.56 to -5.36, p < .001, d = 7.5; ADHD-RS Parents: -9.11, 95% CI = -11.48 to -6.75, p < .001, d = 8.38; CGI-S Self-Report: -0.68, 95% CI = -0.98 to -0.39, p < .001, d = 3.75; CGI-S Clinician: -0.79, 95% CI = -0.95 to -0.62, p < .001; d = 7.71). Functional impairment decreased significantly in the CBT group according to parents (Weiss Functional Impairment Scale -4.02, 95% CI = -7.76 to -0.29, p < .05, d = 2.29) and according to the blinded evaluator (GAF: -7.58, 95% CI = -9.1 to -6.05, p < .001, d = 7.51).
Group CBT associated with pharmacological treatment is an efficacious intervention for reducing ADHD symptoms and functional impairment in adolescents. Clinical trial registration information-CBT Group for Adolescents With ADHD: a Randomized Controlled Trial; http://clinicaltrials.gov/; NCT02172183.
Primary health care (PHC) is central to attainment of the Sustainable Development Goals, yet comparable cross-country data on key aspects of primary care have not been widely available. This study ...analysed data from the People's Voice Survey, which was conducted in 2022 and 2023 in 14 countries. We documented usual source of care across countries and examined associations of usual source of care with core PHC services, quality ratings, and health system confidence. We found that 75% of respondents had a usual source of care, and that 40% of respondents accessed usual care in the public sector at primary level. 44% rated their usual source of care as very good or excellent. Access to PHC-linked screenings and treatments varied widely within and across countries. Having any usual source of care was associated with higher take-up of preventive services, greater access to treatment including mental health services, and greater health system endorsement. Strengthening links between health system users and primary care providers could improve take-up of preventive care and increase user satisfaction with health system performance.
Objective To evaluate the association of hypomagnesemia with prehypertension (preHTN) and hypertension in children. Study design A total of 3954 apparently healthy Mexican children were enrolled in a ...cross-sectional study. Exclusion criteria were type 2 diabetes; hepatic, renal, or endocrine disease; impaired fasting glucose; chronic diarrhea; and intake of vitamins or magnesium supplements in the previous 6 months. preHTN was defined by systolic and/or diastolic blood pressure ≥90th to <95th percentile and hypertension by systolic and/or diastolic blood pressure ≥95th percentile, according to age, sex, and height percentile. Hypomagnesemia was defined by serum magnesium concentration <1.8 mg/dL (<0.74 mmol/L). To control for potential sources of bias related to age, participants were allocated into 2 groups, aged 6-10 years and 11-15 years. Results The prevalence of preHTN and hypertension was 12.2% and 6.4%, respectively, in children aged 6-10 years and 13.9% and 10.6% in those aged 11-15 years. Hypomagnesemia was identified in 59 children with preHTN (27.3%) and 52 (45.6%) with hypertension in the 6-10 year age group, and in 115 children with preHTN (36.0%) and 109 (49.6%) with hypertension in the 11-15 year age group. Adjusted multiple logistic regression analysis showed that in children in both age groups, hypomagnesemia was associated with both preHTN (6-10 years: OR, 2.18, P < .0005; 11-15 years: OR, 1.38, P = .018) and hypertension (6-10 years: OR, 4.87, P < .0005; 11-15 years: OR, 1.83, P = .0002). Conclusion Our results indicate that serum magnesium level <1.8 mg/dL is significantly associated with preHTN and hypertension in apparently healthy children.
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