The influence of neurocognitive impairment, alcohol and other drug (AOD) use, and psychosocial factors on antiretroviral treatment adherence, service utilization and viral load among HIV-seropositive adults

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p<0.01) at 6 months, but not 3 months, post-intervention. Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.

The influence of gene environment interaction on the risk of cognitive impairment: Reducing sexual risk behaviors and alcohol use in HIV-infected adults

Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. ^ A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p^

Argument structure and specific language impairment: retrospect and prospect

This article reflects a collaboration between the Universities of Groningen and Reading of which Frans Zwarts was the promoter. One of the outcomes was a close attention to the learning of various aspects of argument structure by children with specific language impairment (SLI) in Dutch and English. At that time and since, the focus on deficits in grammatical morphology in these children has left verb complementation as something of a syntactic Cinderella. Here we review the findings from our studies in the 1990s. We confirm that children with SLI in both languages have problems with verb specificity, with argument structure alternations and with resultative verb predicates. The very limited number of subsequent studies on verb syntax appear to support our findings. We conclude that this is an area which will repay further scrutiny – it is high time argument structure received an invitation to the ball.

Investigating relative clauses in children with specific language impairment

Background: It is well documented that children with Specific Language Impairment (SLI) experience significant grammatical deficits. While much of the focus in the past has been on their morphosyntactic difficulties, less is known about their acquisition of complex syntactic structures such as relative clauses. The role of memory in language performance has also become increasingly prominent in the literature. Aims: This study aims to investigate the control of an important complex syntactic structure, the relative clause, by school age children with SLI in Ireland, using a newly devised sentence recall task. It also aims to explore the role of verbal and short-termworking memory in the performance of children with SLI on the sentence recall task, using a standardized battery of tests based on Baddeley’s model of working memory. Methods and Procedures: Thirty two children with SLI, thirty two age matched typically developing children (AM-TD) between the ages of 6 and 7,11 years and twenty younger typically developing (YTD) children between 4,7 and 5 years, completed the task. The sentence recall (SR) task included 52 complex sentences and 17 fillers. It included relative clauses that are used in natural discourse and that reflect a developmental hierarchy. The relative clauses were also controlled for length and varied in syntactic complexity, representing the full range of syntactic roles. There were seven different relative clause types attached to either the predicate nominal of a copular clause (Pn), or to the direct object of a transitive clause (Do). Responses were recorded, transcribed and entered into a database for analysis. TheWorkingMemory Test Battery for children (WMTB-C—Pickering & Gathercole, 2001) was administered in order to explore the role of short-term memory and working memory on the children’s performance on the SR task. Outcomes and Results: The children with SLI showed significantly greater difficulty than the AM-TD group and the YTD group. With the exception of the genitive subject clauses, the children with SLI scored significantly higher on all sentences containing a Pn main clause than those containing a transitive main clause. Analysis of error types revealed the frequent production of a different type of relative clause than that presented in the task—with a strong word order preference in the NVN direction indicated for the children with SLI. The SR performance for the children with SLI was most highly correlated with expressive language skills and digit recall. Conclusions and Implications: Children with SLI have significantly greater difficulty with relative clauses than YTD children who are on average two years younger—relative clauses are a delay within a delay. Unlike the YTD children they show a tendency to simplify relative clauses in the noun verb noun (NVN) direction. They show a developmental hierarchy in their production of relative clause constructions and are highly influenced by the frequency distribution of the relative clauses in the ambient language.

The Influence of Gene Environment Interaction on the Risk of Cognitive Impairment: Reducing Sexual Risk Behaviors and Alcohol Use in HIV-infected Adults

Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p

Structural and Functional Lung Impairment in Adult Survivors of Bronchopulmonary Dysplasia

RATIONALE: As more preterm infants recover from severe bronchopulmonary dysplasia (BPD), it is critical to understand the clinical consequences of this condition on the lung health of adult survivors.

OBJECTIVES: To assess structural and functional lung parameters in young adult BPD survivors and preterm and term controls Methods: Young adult survivors of BPD (mean age 24) underwent spirometry, lung volumes, transfer factor, lung clearance index and fractional exhaled nitric oxide measurements together with high-resolution chest tomographic (CT) imaging and cardiopulmonary exercise testing.

MEASUREMENTS AND MAIN RESULTS: 25 adult BPD survivors, (mean ± SD gestational age 26.8 ± 2.3 weeks; birth weight 866 ± 255 g), 24 adult prematurely born non-BPD controls (gestational age 30.6 ± 1.9 weeks; birth weight 1234 ± 207 g) and 25 adult term birth control subjects (gestational age 38.5 ± 0.9 weeks; and birth weight 3569 ± 2979 g) were studied. BPD subjects were more likely to be wakened by cough (OR 9.7, 95% CI: 1.8 to 52.6), p<0.01), wheeze and breathlessness (OR 12.2, 95%CI: 1.3 to 112), p<0.05) than term controls after adjusting for sex and current smoking. Preterm subjects had greater airways obstruction than term subjects. BPD subjects had significantly lower values for FEV1 and FEF25-75 (% predicted and z scores) than term controls (both p<0.001). Although non-BPD subjects also had lower spirometric values than term controls, none of the differences reached statistical significance. More BPD subjects (25%) had fixed airflow obstruction than non-BPD (12.5%) and term (0%) subjects (p=0.004). Both BPD and non-BPD subjects had significantly greater impairment in gas transfer (KCO % predicted) than term subjects (both p<0.05). Eighteen (37%) preterm participants were classified as small for gestational age (birth weight < 10th percentile for gestational age). These subjects had significantly greater impairment in FEV1 (% predicted and z scores) than those born appropriate for gestational age. BPD survivors had significantly more severe radiographic structural lung impairment than non-BPD subjects. Both preterm groups had impaired exercise capacity compared to term controls. There was a trend for greater limitation and leg discomfort in BPD survivors.

CONCLUSIONS: Adult preterm birth survivors, especially those who developed BPD, continue to experience respiratory symptoms and exhibit clinically important levels of pulmonary impairment.

A Validation Study of Vascular Cognitive Impairment Genetics Meta-Analysis Findings in an Independent Collaborative Cohort

Vascular cognitive impairment (VCI), including its severe form, vascular dementia (VaD), is the second most common form of dementia. The genetic etiology of sporadic VCI remains largely unknown. We previously conducted a systematic review and meta-analysis of all published genetic association studies of sporadic VCI prior to 6 July 2012, which demonstrated that APOE (ɛ4, ɛ2) and MTHFR (rs1801133) variants were associated with susceptibility for VCI. De novo genotyping was conducted in a new independent relatively large collaborative European cohort of VaD (nmax = 549) and elderly non-demented samples (nmax = 552). Where available, genotype data derived from Illumina's 610-quad array for 1210 GERAD1 control samples were also included in analyses of genes examined. Associations were tested using the Cochran-Armitage trend test: MTHFR rs1801133 (OR = 1.36, 95% CI 1.16-1.58, p = <0.0001), APOE rs7412 (OR = 0.62, 95% CI 0.42-0.90, p = 0.01), and APOE rs429358 (OR = 1.59, 95% CI 1.17-2.16, p = 0.003). Association was also observed with APOE epsilon alleles; ɛ4 (OR = 1.85, 95% CI 1.35-2.52, p = <0.0001) and ɛ2 (OR = 0.67, 95% CI 0.46-0.98, p = 0.03). Logistic Regression and Bonferroni correction in a subgroup of the cohort adjusted for gender, age, and population maintained the association of APOE rs429358 and ɛ4 allele.

The association between spastic Cerebral Palsy, intellectual impairment, and gestational age: results from the Northern Ireland Cerebral Palsy Register

Background
Studies suggest a complex relationship between Cerebral Palsy sub-types, severity of impairment, and risk factors such as gestational age. To investigate these relationships, we conducted analyses on over 1,100 children included in the Northern Ireland Cerebral Palsy Register (NICPR) whose clinical CP subtype was Bilateral Spastic or Spastic Hemiplegia, and for whom information was available on the relevant variables.
Methods
We tested for the association between Bilateral and Hemiplegia subtypes, severe intellectual impairment, and gestational age (term; moderately preterm; very or extremely preterm) while controlling for gender, socio-economic deprivation, year of birth, and birth weight (using a standardized birth-weight score based on deviance from the birth weight average within each gestational age band). Severity of intellectual impairment was dichotomised (severe intellectual delay vs. moderate or no delay).
Results
Logistic regressions indicated a good fit of the model, and the predictors included explained approximately 19% of variability in the outcome. The results indicated a strong association between the Bilateral subtype and severe intellectual impairment: compared to children with the Hemiplegia subtype, those with Bilateral Spastic CP displayed a 10-fold increase in the odds of severe intellectual impairment. The results revealed a significant interaction between CP subtype and gestational age: for the Bilateral CP subtype, being born at term was associated with increased probability of severe intellectual impairment.
Discussion
Results are consistent with other studies (Hemming et al., 2008) in indicating that the likelihood of cognitive impairments increases with increasing gestational age at delivery of Bilateral Spastic CP children. The results are discussed in light of hypotheses that suggest the brain might be able to reorganise and compensate the effects of lesions and injuries when it is still less developed.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment (Review)

Background

It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
Objectives

To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
Search methods

We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
Selection criteria

Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
Data collection and analysis

Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
Main results

Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
Authors' conclusions

Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Big Bath and Impairment of Goodwill : A study of the European telecommunications industry

Income decreasing strategies conducted by management could be harmful for various stakeholders. One example is big bath accounting, which could be accomplished in numer- ous ways. This study focus on big baths achieved by recognising impairments of goodwill. Purpose - The purpose of this study is to examine patterns of association between big bath accounting and impairment of goodwill within the telecommunication service industry in Europe. Further, this study aim at contributing to the discussion regarding utilisation of big baths through impairments of goodwill, and takes the perspective of an external stakehold- er. Delimitations - The study is restricted to European telecommunication entities comprised in STOXX Europe 600 Index. Method - This study was conducted using a hybrid of qualitative and quantitative research strategy with a deductive approach. The five indicators used to identify various big bath behaviours were inspired and derived from theory and previous research. Data from 2009 to 2015 was collected from the companies’ annual reports and websites, and analysed by the help of codification of each fulfilled indicator where 2009 merely served as a compara- tive year for 2010. By the use of a scoreboard the collected data was summarised on an ag- gregated yearly basis as the industry, not the specific companies, were analysed. Empirical findings - The results of this study suggests that big baths are executed among tele- communication companies within Europe. These are conducted simultaneously as impair- ments of goodwill are present, facilitated by earning management. A possible explanation is considered to be the room for interpretation inherent in IAS 36, enabling goodwill impair- ments to be recognised on managers’ command. Thereby an impairment could be “saved” for better or worse circumstances, or recognised when there exist an opportunity to max- imise (the manager's) wealth in the future. This study reveal the co-occurrence of goodwill impairments and big bath-indications, however a review of causal relationships are not en- abled by the limitations of the chosen method. 

Outcome analysis of intracorneal ring segments for the treatment of keratoconus based on visual, refractive, and aberrometric impairment

PURPOSE: To analyze the outcomes of intracorneal ring segment (ICRS) implantation for the treatment of keratoconus based on preoperative visual impairment. DESIGN: Multicenter, retrospective, nonrandomized study. METHODS: A total of 611 eyes of 361 keratoconic patients were evaluated. Subjects were classified according to their preoperative corrected distance visual acuity (CDVA) into 5 different groups: grade I, CDVA of 0.90 or better; grade II, CDVA equal to or better than 0.60 and worse than 0.90; grade III, CDVA equal to or better than 0.40 and worse than 0.60; grade IV, CDVA equal to or better than 0.20 and worse than 0.40; and grade plus, CDVA worse than 0.20. Success and failure indices were defined based on visual, refractive, corneal topographic, and aberrometric data and evaluated in each group 6 months after ICRS implantation. RESULTS: Significant improvement after the procedure was observed regarding uncorrected distance visual acuity in all grades (P < .05). CDVA significantly decreased in grade I (P < .01) but significantly increased in all other grades (P < .05). A total of 37.9% of patients with preoperative CDVA 0.6 or better gained 1 or more lines of CDVA, whereas 82.8% of patients with preoperative CDVA 0.4 or worse gained 1 or more lines of CDVA (P < .01). Spherical equivalent and keratometry readings showed a significant reduction in all grades (P ≤ .02). Corneal higher-order aberrations did not change after the procedure (P ≥ .05). CONCLUSIONS: Based on preoperative visual impairment, ICRS implantation provides significantly better results in patients with a severe form of the disease. A notable loss of CDVA lines can be expected in patients with a milder form of keratoconus.

Attention Deficit Hyperactivity Disorder and Executive Function Impairment: An Overview.

As with any cognitive ability, attention is vulnerable to dysfunction. The most common attentional problem is attention deficit hyperactivity disorder (ADHD). This brief overview will highlight the symptoms and deficits associated with ADHD, its prevalence in today’s society, the association between executive function impairment and ADHD using Barkley’s (1997) work, and the personal and societal effects of the disorder.

Dose-Adjusted Beta-Lactam Antibiotic-Induced Encephalopathy in a Patient with End-Stage Renal Impairment: A Case Report

Introduction: Despite adherence to current guidelines regarding dose adjustment and drug-level monitoring, beta-lactam-induced encephalopathy can still occur in the setting of chronic renal impairment. Case Report: We report what we believe is the first case of piperacillin- and tazobactam-induced encephalopathy in a patient with pre-existing cefepime-induced encephalopathy in the context of end-stage kidney disease despite adequate dose adjustment for renal impairment.