Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington’s disease (HD) is inconsistent. Understanding such impairments may help to better understand early ...functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (
p
< 0.001) and reacted slower (
p
< 0.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (
p
< 0.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (
p
< 0.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group.
Background
Precision medicine aims to identify those patients who will benefit the most from specific treatments. Recent work found large effects of naltrexone among “reward drinkers,” defined as ...individuals who drink primarily for the rewarding effects of alcohol. This study sought to replicate and extend these recent findings by examining whether the desire to drink mediated the effect of naltrexone among reward drinkers.
Methods
We conducted a secondary analysis of a 12‐week randomized clinical trial of daily or targeted naltrexone among problem drinkers (n = 163), with a focus on 86 individuals (n = 45 naltrexone and n = 41 placebo) who received daily medication. Interactive voice response technology was used to collect daily reports of drinking and desire to drink. Factor mixture models were used to derive reward and relief phenotypes. Moderation analyses were used to evaluate naltrexone effects, with phenotype as a moderator variable. Multilevel mediation tested average desire to drink as a mediator.
Results
Results indicated 4 phenotypes: low reward/low relief; low reward/high relief; high reward/low relief; and high reward/high relief. There was an interaction between the high reward/low relief subgroup (n = 10) and daily naltrexone versus placebo on drinks per drinking day (DPDD; p = 0.03), percent heavy drinking days (p = 0.004), and daily drinking (p = 0.02). As compared to placebo, individuals in the high reward/low relief phenotype who received daily naltrexone had significantly fewer DPDD (Cohen's d = 2.05) and had a lower proportion of heavy drinking days (Cohen's d = 1.75). As hypothesized, reductions in average desire to drink mediated the effect of naltrexone on average daily drinking among the high reward/low relief drinkers (moderated mediation effect: p = 0.029).
Conclusions
This theory‐driven study replicates the empirical finding that naltrexone is particularly efficacious among high reward/low relief drinkers. Our study brings the field a step closer to the potential of using a precision medicine approach to treating alcohol use disorder.
In a post‐hoc precision medicine analysis of a 12‐week clinical trial, the current study examined the efficacy of naltrexone versus placebo for reward drinkers, individuals who drink primarily for the rewarding effects of alcohol and not for the relieving effects. As compared to placebo, reward drinkers who received naltrexone (50 mg/d) had significantly fewer drinks per drinking day (see Figure, Cohen's d = 2.05). Reductions in average desire to drink mediated the effect of naltrexone on average daily drinking among reward drinkers.
MTI has the potential to detect abnormalities in normal-appearing white and gray matter on conventional MR imaging. Early detection methods and disease progression markers are needed in HD research. ...Therefore, we investigated MTI parameters and their clinical correlates in premanifest and manifest HD.
From the Leiden TRACK-HD study, 78 participants (28 controls, 25 PMGC, 25 MHD) were included. Brain segmentation of cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed using FSL's automated tools FAST and FIRST. Individual MTR values were calculated from these regions and MTR histograms constructed. Regression analysis of MTR measures from all gene carriers with clinical measures was performed.
MTR peak height was reduced in both cortical gray (P = .01) and white matter (P = .006) in manifest HD compared with controls. Mean MTR was also reduced in cortical gray matter (P = .01) and showed a trend in white matter (P = .052). Deep gray matter structures showed a uniform pattern of reduced MTR values (P < .05). No differences between premanifest gene carriers and controls were found. MTR values correlated with disease burden and motor and cognitive impairment.
Throughout the brain, disturbances in MTI parameters are apparent in early HD and are homogeneous across white and gray matter. The correlation of MTI with clinical measures indicates the potential to act as a disease monitor in clinical trials. However, our study does not provide evidence for MTI as a marker in premanifest HD.
Randomized trials of medications for alcohol dependence (AD) often report no differences between active medications. Few studies in AD have tested hypotheses regarding which medication will work best ...for which patients (ie, precision medicine). The PREDICT study tested acamprosate and naltrexone vs placebo in 426 randomly assigned AD patients in a 3-month treatment. PREDICT proposed individuals whose drinking was driven by positive reinforcement (ie, reward drinkers) would have a better treatment response to naltrexone, whereas individuals whose drinking was driven by negative reinforcement (ie, relief drinkers) would have a better treatment response to acamprosate. The goal of the current analysis was to test this precision medicine hypothesis of the PREDICT study via analyses of subgroups. Results indicated that four phenotypes could be derived using the Inventory of Drinking Situations, a 30-item self-report questionnaire. These were high reward/high relief, high reward/low relief, low reward/high relief, and low reward/low relief phenotypes. Construct validation analyses provided strong support for the validity of these phenotypes. The subgroup of individuals who were predominantly reward drinkers and received naltrexone vs placebo had an 83% reduction in the likelihood of any heavy drinking (large effect size). Cutoff analyses were done for clinical applicability: individuals are reward drinkers and respond to naltrexone if their reward score was higher than their relief score AND their reward score was between 12 and 31. Using naltrexone with individuals who are predominantly reward drinkers produces significantly higher effect sizes than prescribing the medication to a more heterogeneous sample.
Primary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative ...risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS).
Comparative series.
One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study.
Samples of DNA were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls) between 1994 and 2009. The frequencies of 13 risk alleles previously associated with POAG or with optic disc features in other cohorts were compared between POAG cases and controls in the OHTS cohort using analyses of variance. The 2 largest subgroups, non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%), also were analyzed separately. The probability of glaucoma developing over the course of the OHTS was compared between participants stratified for transmembrane and coiled-coil domains 1 (TMCO1) risk alleles using Kaplan-Meier and Cox proportional hazards analyses.
Association of POAG with known genetic factors.
No association was detected between the known POAG risk alleles when the OHTS cohort was examined as a whole. However, in the subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were statistically different between cases and controls (P = 0.00028). By 13 years, non-Hispanic white participants with TMCO1 risk alleles had a 12% higher cumulative frequency of glaucoma developing than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures (i.e., intraocular pressure).
The size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase the risk of glaucoma developing among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that long have been associated with glaucoma.
Higher education authorities strive towards a transformed, democratic, non-racist, non-sexist system which will, inter alia, promote a democratic ethos and human rights culture through educational ...programmes and practices that will foster creative thinking, cultural tolerance and a collective commitment to reach the ideals of a humane, non-sexist and non-racist society. The critical cross-field outcomes that must be demonstrably achieved by any programme approved in terms of the National Qualifications Framework echo these ideals. Law faculties typically refer to their Jurisprudence modules to demonstrate compliance with the requirements that students should understand the world as a set of related systems and be sensitive to different cultures, meanings and perceptions across a range of social contexts. However, the design and presentation of such modules should be reconsidered. It is argued that the ideas of the liberal pragmatist Richard Rorty (1931-2007) provide valuable insights into these aspects and that a new justification for inclusion of Jurisprudence in law curricula is, in fact, established through it. Kritieke kruisvelduitkomste : 'n Rortiaanse siening oor waarom en hoe om Regsfilosofie te doseer in Suid-Afrika in die 2010's Hoëronderwysowerhede moet streef na 'n getransformeerde, demokratiese, nie-rassistiese, nie-seksistiese stelsel wat onder meer 'n demokratiese etos moet bevorder deur opvoedkundige programme en praktyke wat kreatiewe denke, kulturele verdraagsaamheid en 'n kollektiewe verbondenheid tot 'n nie-rassistiese, nie-seksistiese samelewing sal kweek. Hierdie ideale word herhaal in die kritieke kruisvelduitkomste waarvan die bereiking gedemonstreer moet word alvorens enige program ingevolge die Nasionale Kwalifikasieraamwerk goedgekeur word. Regsfakulteite verwys tipies na hul Regsfilosofie-modules wanneer daar bewys moet word dat studente die wêreld verstaan as 'n stel verwante sisteme en dat hulle sensitief is teenoor verskillende kulture, menings en persepsies in verskillende sosiale kontekste. Die ontwerp en aanbieding van sodanige modules moet egter heroorweeg word. Daar word geargumenteer dat die idees van die liberale pragmatis Richard Rorty (1931-2007) waardevolle insigte bied in hierdie verband en dat daar inderdaad 'n nuwe regverdiging bestaan vir die insluiting van Regsfilosofie in regskurrikula.
1 Center for Activity and
Ageing, School of Kinesiology, Faculty of Health Sciences,
2 Department of Anatomy and
Cell Biology, Faculty of Medicine, and
3 School of Physical Therapy,
Faculty of ...Health Sciences, The University of Western Ontario,
London, Ontario, Canada N6A 3K7
The effects of aging on motoneuron firing rates and muscle
contractile properties were studied in tibialis anterior muscle by
comparing results from six young (20.8 ± 0.8 yr) and six old men
(82.0 ± 1.7 yr). For each subject, data were collected from repeated tests over a 2-wk period. Contractile tests included maximal
voluntary contraction (MVC) with twitch interpolation and stimulated
twitch contractions. The old men had 26% lower MVC torque
( P < 0.01) than did the young men,
but percent activation was not different (99.1 and 99.3%,
respectively). Twitch contraction durations were 23% longer
( P < 0.01) in the old compared with the young men. During a series of repeated brief steady-state contractions at 10, 25, 50, 75, and 100% MVC, motor unit firing rates
were recorded. Results from ~950 motor unit trains in each subject
group indicated that at all relative torque levels mean firing rates
were 30-35% lower ( P < 0.01)
in the old subjects. Comparisons between young and old subjects' mean
firing rates at each of 10%, 50%, and MVC torques and their
corresponding mean twitch contraction duration yielded a range of
moderate-to-high correlations ( r = 0.67 to 0.84). That lower firing rates were matched to
longer twitch contraction durations in the muscle of old men, and
relatively higher firing rates were matched with shorter contraction
times from the young men, indirectly supports the neuromuscular
age-related remodeling principle.
aging; intramuscular electromyography; neuromuscular remodeling; strength; dorsiflexors
Summary
Aim: The Patient Education Programme for Parkinson’s disease (PEPP) was assessed in a recent randomised controlled trial (RCT). In this study, a trend was identified towards significant ...improvement of patients’ quality of life (Qol) as well as a significant reduction of caregivers’ psychosocial burden and need for help. This study is aimed at evaluating the effectiveness of the PEPP in clinical practice as compared with the RCT in an academic setting. The second aim is to assess its effectiveness in clinical practice at 6‐month follow‐up.
Methods: Fifty‐five patients and 50 caregivers from nine clinical settings participated in the PEPP consisting of eight weekly sessions of 90 min. Self‐report questionnaires were used to assess patients’ Qol (PDQ‐39) and caregivers’ psychosocial burden and need for help (BELA‐A‐k) at baseline, directly after the programme and at 6‐month follow‐up. To compare the baseline data and short‐term effects, data were used from an RCT study which included 64 Parkinson’s disease patients and 46 caregivers.
Results: Compared with the RCT control group, significant effects, after Bonferoni adjustment, were found for patients’ Qol as well as for caregivers’ psychosocial burden and need for help. No significant changes were found between baseline scores compared with 6‐month follow‐up. Scores returned to baseline levels at 6‐month follow‐up.
Conclusions: Effects from the RCT study were replicated and the effect on patients’ Qol was now significant. However, at 6‐month follow‐up, scores returned to baseline levels, indicating the need for some form of a booster session.
Although parents experience grief when confronted with their child's deterioration and imminent death, most bereavement care is focused on supporting parents after child loss. Insight into intentions ...and strategies of the health care professionals (HCPs) in preloss care during the end of life is still lacking.
To create a starting point for improvement of preloss care, this study explores HCPs' experiences with providing support aimed at parental feelings of grief during the child's end of life.
Exploratory qualitative research using individual semistructured interviews with clinicians in pediatrics and neonatology in hospital and homecare settings. Data were thematically analyzed by a multidisciplinary team.
Nineteen HCPs participated. HCPs tried to ensure that parents could reflect on the care received as concordant to their preferences and were not hindered in their bereavement as a consequence of their professional actions. Strategies included maximizing parental presence, enabling parental involvement in decision making, and ensuring a dignified death. While using these strategies, HCPs faced several difficulties: uncertainty about the illness course, unpredictability of parental grief responses, and being affected themselves by the child's imminent death. It helped HCPs to develop a bond with parents, find comfort with colleagues, and making joint decisions with colleagues.
HCPs strive to improve parental coping after the child's death, yet apply strategies that positively influence parental preparedness and well-being during the end of life as well. Individual HCPs are left with many uncertainties. A more robust approach based on theory, evidence, and training is needed to improve preloss care in pediatrics.
Bereavement care for parents predominantly focuses on care after child loss. However, Health Care Professionals (HCPs) feel responsible for supporting parents who are grieving losses in their child's ...end-of-life. Preloss care is tailored to the parents’ needs, thus highly varying. To better understand the nature of preloss care, this study aims to gain insight into the challenges HCPs encounter while providing care for parents during their child's end-of-life.
Exploratory qualitative research using semistructured interviews with physicians and nurses working in neonatology and pediatrics in 3 university pediatric hospitals and 1 child home care service. A multidisciplinary team thematically analyzed the data.
Twenty-two HCPs participated in this study. From the HCPs' inner perspective, three dyadic dimensions in preloss care delivery were identified that create tension in HCPs: sustaining hope versus realistic prospects, obtaining emotional closeness versus emotional distance, and exploring emotions versus containing emotions. Throughout preloss care delivery, HCPs weighed which strategies to use based on their perception of parental needs, the situation, and their own competencies. HCPs remained with lingering uncertainties on whether the preloss care they provide constituted optimal care.
As a result of the experienced tension, HCPs are at risk for prolonged distress and possibly even compassion fatigue. In order to maintain a positive emotional balance in HCPs, education should focus on adapting positive coping strategies and provide hands-on training. Furthermore, on an institutional level a safe environment should be fostered and well-being could be enhanced through learning by sharing as a team.
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