Several characteristics associated with increased risk for Parkinson's disease (PD) have been identified, including specific genotypes and various non-motor symptoms. Characterizing non-motor ...features, such as cognitive abilities, among individuals considered at-risk for PD is essential to improving prediction of future neurodegeneration.
Participants belonging to the following cohorts of the Parkinson Progression Markers Initiative (PPMI) study were included: de novo PD with dopamine transporter binding deficit (n = 423), idiopathic REM sleep behavior disorder (RBD, n = 39), hyposmia (n = 26) and non-PD mutation carrier (NMC; Leucine-rich repeat kinase 2 (LRRK2) G2019S (n = 88) and glucocerebrosidase (GBA) gene (n = 38) mutations)). Inclusion criteria enriched the RBD and hyposmia cohorts, but not the NMC cohort, with individuals with dopamine transporter binding deficit. Baseline neuropsychological performance was compared, and analyses were adjusted for age, sex, education, and depression.
The RBD cohort performed significantly worse than the hyposmia and NMC cohorts on Symbol Digit Modality Test (mean (SD) 32.4 (9.16) vs. 41.8 (9.98), p = 0.002 and vs. 45.2 (10.9), p<0.001) and Judgment of Line Orientation (11.3 (2.36) vs.12.9 (1.87), p = 0.004 and vs. 12.9 (1.87), p<0.001). The RBD cohort also performed worse than the hyposmia cohort on the Montreal Cognitive Assessment (25.5 (4.13) vs. 27.3 (1.71), p = 0.02). Hyposmics did not differ from PD or NMC cohorts on any cognitive test score.
Among individuals across a spectrum of risk for PD, cognitive function is worse among those with the characteristic most strongly associated with future risk of PD or dementia with Lewy bodies, namely RBD.
Physician-pharmacist collaboration improves blood pressure, but there is little information on whether this model can reduce the gap in healthcare disparities. This trial involved 32 medical offices ...in 15 states. A clinical pharmacist was embedded within each office and made recommendations to physicians and patients in intervention offices. The purpose of the present analysis was to evaluate whether the pharmacist intervention could reduce healthcare disparities by improving blood pressure in high-risk racial and socioeconomic subjects compared with the control group. The analyses in minority subjects were prespecified secondary analyses, but all other comparisons were secondary, post hoc analyses. The 9-month visit was completed by 539 patients: 345 received the intervention, and 194 were in the control group. Following the intervention, mean systolic blood pressure was found to be 7.3 mm Hg (95% confidence interval 2.4, 12.3) lower in subjects from racial minority groups who received the intervention compared with the control group (P=0.0042). Subjects with ≤12 years of education in the intervention group had a systolic blood pressure 8.1 mm Hg (95% confidence interval 3.2, 13.1) lower than the control group with lower education (P=0.0001). Similar reductions in blood pressure occurred in patients with low incomes, those receiving Medicaid, or those without insurance. This study demonstrated that a pharmacist intervention reduced racial and socioeconomic disparities in the treatment of blood pressure. Although disparities in blood pressure were reduced by the intervention, there were still nonsignificant gaps in mean systolic blood pressure when compared with intervention subjects not at risk.
URL: http://clinicaltrials.gov. Unique identifier: NCT00935077.
Across three studies, we develop a model of the direct and indirect paths through which the perceived prevalence (perceived descriptive norms PDN) of intimate partner violence (IPV) among peers may ...influence individuals’ likelihood of engaging in IPV. Study 1 replicated and extended previous cross-sectional research by demonstrating a positive longitudinal association between PDN and subsequent IPV perpetration. Study 2 further showed the influence of PDN on IPV perpetration to be mediated through its relation to perceived peer acceptance of IPV (perceived injunctive norms PIN), which in turn predicted personal IPV acceptance. Study 3 built on this model using an experimental paradigm to show that increasing PDN leads to corresponding increases in PIN and, in turn, personal IPV acceptance, which both predicted IPV perpetration. Furthermore, the effects of PIN on personal IPV acceptance and IPV propensity were strongest for dominance-oriented individuals. Results bear important implications for social norms–based interventions for IPV.
Background
Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of ...school, work, and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents, this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents.
Methods
CHAMP is a double‐blinded, placebo‐controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real‐world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8‐week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28‐day baseline and the final 28 days of treatment (weeks 20‐24).
Conclusions
The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and adolescents and subsequently improve the disability and outcomes.
While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable ...clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.
To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) ...biosynthesis.
We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461). Primary endpoints were safety and biochemical efficacy as determined by change in plasma Neu5Ac and sarcolemmal sialylation. Clinical efficacy was evaluated using secondary outcome measures as part of study extensions, and a disease progression model (GNE-DPM) was tested as an efficacy analysis method.
Most drug-related adverse events were gastrointestinal, and there were no serious adverse events. Increased plasma Neu5Ac (+2,159 nmol/L, p < 0.0001) and sarcolemmal sialylation (p = 0.0090) were observed at day 90 compared to baseline. A slower rate of decline was observed for upper extremity strength (p = 0.0139), lower extremity strength (p = 0.0006), and the Adult Myopathy Assessment Tool (p = 0.0453), compared to natural history. Decreased disease progression was estimated at 12 (γ = 0.61 95% CI: 0.09, 1.27) and 18 months (γ = 0.55 95% CI: 0.12, 1.02) using the GNE-DPM.
ManNAc showed long-term safety, biochemical efficacy consistent with the intended mechanism of action, and preliminary evidence clinical efficacy in patients with GNE myopathy.
In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ
), phosphorylated tau ...181 (p-tau
), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau
and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ
. First, we describe longitudinal trajectories of biofluid markers in PD. Second, we modified the AD β-amyloid/tau/neurodegeneration (ATN) framework for application in PD (ATN
) using CSF Aβ
(A), p-tau
(T), and serum NfL (N) and tested ATN
prediction of longitudinal cognitive decline in PD.
Participants were selected from the Parkinson's Progression Markers Initiative cohort, clinically diagnosed with sporadic PD or as controls, and followed up annually for 5 years. Linear mixed-effects models (LMEMs) tested the interaction of diagnosis with longitudinal trajectories of analytes (log transformed, false discovery rate FDR corrected). In patients with PD, LMEMs tested how baseline ATN
status (AD A+T+N± vs not) predicted clinical outcomes, including Montreal Cognitive Assessment (MoCA; rank transformed, FDR corrected).
Participants were 364 patients with PD and 168 controls, with comparable baseline mean (±SD) age (patients with PD = 62 ± 10 years; controls = 61 ± 11 years; Mann-Whitney Wilcoxon:
= 0.4) and sex distribution (patients with PD = 231 male individuals 63%; controls = 107 male individuals 64%; χ
:
= 1). Patients with PD had overall lower CSF p-tau
(β = -0.16, 95% CI -0.23 to -0.092,
= 2.2e-05) and t-tau than controls (β = -0.13, 95% CI -0.19 to -0.065,
= 4e-04), but not Aβ
(
= 0.061) or NfL (
= 0.32). Over time, patients with PD had greater increases in serum NfL than controls (β = 0.035, 95% CI 0.022 to 0.048,
= 9.8e-07); slopes of patients with PD did not differ from those of controls for CSF Aβ
(
= 0.18), p-tau
(
= 1), or t-tau (
= 0.96). Using ATN
, PD classified as A+T+N± (n = 32; 9%) had worse cognitive decline on global MoCA (β = -73, 95% CI -110 to -37,
= 0.00077) than all other ATN
statuses including A+ alone (A+T-N-; n = 75; 21%).
In patients with early PD, CSF p-tau
and t-tau were low compared with those in controls and did not increase over 5 years of follow-up. Our study shows that classification using modified ATN
(incorporating CSF Aβ
, CSF p-tau
, and serum NfL) can identify biologically relevant subgroups of PD to improve prediction of cognitive decline in early PD.
Conflicting reports have caused controversy on whether cysticidal drugs modify the natural course of neurocysticercosis.
To perform a meta-analysis of randomized trials assessing the effect of ...cysticidal drugs on neuroimaging and clinical outcomes of patients with neurocysticercosis.
Search of MEDLINE, Cochrane Database of Systematic Reviews, and Literatura Latino-Americana y del Caribe en Ciencias de la Salud (LILACS) between 1979 and 2005. There were no language restrictions.
Randomized trials of cysticidal drug therapy for neurocysticercosis that met predefined criteria designed to allow characterization of the disease and objective evaluation of therapy. The authors independently reviewed articles. Abstracted data included study design, number of randomly assigned patients and withdrawals, intervention, adverse events, timing of neuroimaging studies, and outcomes.
Eleven studies met the inclusion criteria. Six trials randomly assigned 464 patients with cystic lesions (vesicular cysticerci), and 5 trials randomly assigned 478 patients with enhancing lesions (colloidal cysticerci). Parasites were located in the brain parenchyma or subarachnoid space at the convexity of the cerebral hemispheres. Cysticidal drug therapy was associated with complete resolution of cystic lesions (44% vs. 19%; P = 0.025). Trials on enhancing lesions showed a trend toward lesion resolution favoring the use of cysticidal drugs (72% vs. 63%; P = 0.38) that became statistically significant when an outlier trial was excluded from the analysis (69% vs. 55%; P = 0.006). Risk for seizure recurrence was lower after cysticidal treatment in patients with enhancing lesions (14% vs. 37%; P < 0.001). The single trial evaluating the frequency of seizures in patients with cystic lesions showed a 67% reduction in the rate of generalized seizures with treatment (P = 0.006).
Not all studies focused on the control of seizures as an outcome.
Cysticidal drug therapy results in better resolution of colloidal and vesicular cysticerci, lower risk for recurrence of seizures in patients with colloidal cysticerci, and a reduction in the rate of generalized seizures in patients with vesicular cysticerci.
There is clinical and phenotypic heterogeneity in
G2019S Parkinson disease (PD), including loss of smell. Olfactory scores have defined subgroups of
PD at baseline. We now extend this work ...longitudinally to better determine features associated with olfactory classes and to gain further insight into this heterogeneity.
Evaluation of 162 patients with
PD and 198 patients with idiopathic PD (IPD) from the
Ashkenazi Jewish Consortium was performed, with follow-up available for 92 patients with
PD and 74 patients with IPD. Olfaction (University of Pennsylvania Smell Identification Test UPSIT), motor function (Unified Parkinson Disease Rating Scale), and cognition (Montreal Cognitive Assessment), as well as sleep, nonmotor, and mood, were measured. Gaussian mixture models were applied on the UPSIT percentile score to determine subgroups based on olfactory performance. Linear mixed effects models, using PD duration as the time scale, assessed the relationship between UPSIT subgroup membership and motor/cognitive change.
Baseline olfaction was better in
PD compared with IPD (mean UPSIT ± SD: 24.2 ± 8.8 vs 18.9 ± 7.6), with higher mean percentile scores (difference: 15.3 ± 11.6) (
< 0.001) and less frequent hyposmia (55.6% vs 85.4%;
< 0.001). Analysis suggested 3 classes among
PD. Age at onset in
PD was earlier in the worst olfaction group (group 1), compared with groups 2 and 3 (54.5 ± 11.1 vs 61.7 ± 9.3) (
= 0.012), and separately in the hyposmic group overall (55.0 ± 11.3 vs 61.7 ± 9.1) (
< 0.001). Longitudinal motor deterioration in
PD was also significantly faster in the worst UPSIT group than the best UPSIT group (group 3 vs group 1: B = 0.31, SE = 0.35 vs B = 0.96, SE = 0.28) (rate difference = -0.65, SE = 0.29) (
= 0.03). However, olfactory group membership was not significantly associated with cognitive decline.
In this large
cohort with longitudinal analysis, we extend prior work demonstrating subgroups defined by olfaction in
G2019S PD and show that the worst olfaction group has earlier age at PD onset and more rapid motor decline. This supports a subgroup of
PD that might show more rapid change in a clinical trial of
-related agents and highlights the need to integrate careful phenotyping into allocation schema in clinical trials of
-related agents.
This study provides Class II evidence that worse olfactory scores were associated with an earlier age at symptomatic onset and a faster rate of motor deterioration in patients with
PD.
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