Severe Cognitive Problems Research Articles

Decoding IBS: a machine learning approach to psychological distress and gut-brain interaction

PurposeIrritable bowel syndrome (IBS) is a diagnosis defined by gastrointestinal (GI) symptoms like abdominal pain and changes associated with defecation. The condition is classified as a disorder of the gut-brain interaction (DGBI), and patients with IBS commonly experience psychological distress. The present study focuses on this distress, defined from reports of fatigue, anxiety, depression, sleep disturbances, and performance on cognitive tests. The aim was to investigate the joint contribution of these features of psychological distress in predicting IBS versus healthy controls (HCs) and to disentangle clinically meaningful subgroups of IBS patients.MethodsIBS patients (n=49\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n = 49$$\\end{document}) and HCs (n=28\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$n = 28$$\\end{document}) completed the Chalder Fatigue Scale (CFQ), the Hamilton Anxiety and Depression Scale (HADS), and the Bergen Insomnia Scale (BIS), and performed tests of memory function and attention from the Repeatable Battery Assessing Neuropsychological Symptoms (RBANS). An initial exploratory data analysis was followed by supervised (Random Forest) and unsupervised (K-means) classification procedures.ResultsThe explorative data analysis showed that the group of IBS patients obtained significantly more severe scores than HCs on all included measures, with the strongest pairwise correlation between fatigue and a quality measure of sleep disturbances. The supervised classification model correctly predicted belongings to the IBS group in 80% of the cases in a test set of unseen data. Two methods for calculating feature importance in the test set gave mental and physical fatigue and anxiety the strongest weights. An unsupervised procedure with K=3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$K = 3$$\\end{document} showed that one cluster contained 24% of the patients and all but two HCs. In the two other clusters, their IBS members were overall more impaired, with the following differences. One of the two clusters showed more severe cognitive problems and anxiety symptoms than the other, which experienced more severe problems related to the quality of sleep and fatigue. The three clusters were not different on a severity measure of IBS and age.ConclusionThe results showed that psychological distress is an integral component of IBS symptomatology. The study should inspire future longitudinal studies to further dissect clinical patterns of IBS to improve the assessment and personalized treatment for this and other patient groups defined as disorders of the gut-brain interaction. The project is registered at https://classic.clinicaltrials.gov/ct2/show/NCT04296552 20/05/2019.

Cognitive Function and Variability in Antipsychotic Drug–Naive Patients With First-Episode Psychosis

Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated. To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls. In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022. Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included. Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias. The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability. Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92). Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

Work Productivity Among Younger Breast Cancer Survivors: The Impact of Behavioral Interventions for Depression

ObjectivesThe Pathways to Wellness randomized controlled trial found that 2 behavioral interventions, mindfulness awareness practices and survivorship education, reduced depressive symptoms in younger breast cancer survivors (BCSs) compared with wait-list control. This secondary analysis examines whether the interventions led to reduced loss of work productivity among younger BCSs and whether such reductions were mediated by reductions in depressive symptoms. MethodsThe Work Productivity and Activity Impairment scale was used to measure work productivity loss at 4 assessment time points. Correlates of productivity loss at enrollment were examined using multivariable linear regression. Differences in change over time in productivity loss between each intervention group and control were assessed using linear mixed models. Reduced depressive symptoms were tested as a mediator of reduced productivity loss. ResultsOf 247 trial participants, 199 were employed and included in the analyses. At enrollment, higher productivity loss was associated with chemotherapy receipt (P = .003), younger age (P = .021), more severe cognitive problems (P = .002), higher musculoskeletal pain severity (P = .002), more depressive symptoms (P = .016), and higher fatigue severity (P = .033). The mindfulness intervention led to significantly less productivity loss compared with control at all 3 postintervention assessment points (all P < .05), with about 54% of the effect mediated by reduction in depressive symptoms. Survivorship education was not associated with reduced loss of productivity. ConclusionsThese findings suggest that addressing depressive symptoms through behavioral interventions, such as mindfulness, may mitigate impacts on work productivity in younger BCSs.

P76: Agreement between nursing-home caregivers’ observations of residents’ depression, wellbeing, and quality of life

Objective:In nursing home residents, outcomes are often assessed using proxies, especially in residents with severe cognitive problems. Although caregivers are commonly involved as proxies, studies assessing their agreement for proxy measures are scarce. Therefore, secondary analysis was performed on a dataset with proxy-reported scores of several scales in Dutch and Flemish nursing home residents with and without dementia.Methods:To assess the agreement between the observations of 81 pairs of caregivers, we calculated Cohen’s Kappa, Weighted Kappa, and Prevalence- and Bias-Adjusted Kappa (PABAK and PABAK- OS for ordinal data) coefficients for the items on the Nijmegen observer-rated depression scale for detection of depression in nursing home residents (NORD), the social wellbeing of nursing-home residents scale (SWON-3), and two subscales (i.e., “social relations” and “having something to do”) of the QUALIDEM. In addition, coefficients were calculated for the item concerning subjective judgment of the residents’ depressive symptoms (“no,” “yes, mild or light,” or “yes, severe”) and for the item concerning whether the caregivers believed a depression diagnosis had been established (“yes,” “no”).Results:In general, PABAK and PABAK-OS coefficients were higher than the Cohen’s and Weighted Kappa coefficients, suggesting a considerable amount of prevalence or bias. For the total sample, most items were above .40, indicating acceptable agreement. The results showed higher levels of agreement for proxy scores of residents with lower levels of dementia, compared to residents with more severe dementia.Conclusion:The general finding of different levels of agreement between coefficients with and without correction for prevalence and bias, suggest the importance of exploring both values to enable adequate interpretation of the reliability of these items. The result of limited levels of agreement between caregivers concerning residents with more severe dementia underscores challenges for measurements in this population. We believe that practitioners and researchers should be aware of these challenges when using and interpreting scores derived from proxies. Moreover, understanding why different raters reach different conclusions regarding the same residents is important for interpreting the meaning of proxy-reported scores.

Exploring the association between self-care behaviour, knowledge and cognition in patients with heart failure: a secondary analysis from the HF-Wii study

Abstract Background Self-care is vital for patients with heart failure and is influenced by different factors, Knowledge and the ability to reflect on behaviors is important to make decisions on self-care. Cognition may also be an important factor in relation to both knowledge and self-care. It has been found that cognitive impairment in patients with heart failure is common, with a reported prevalence of 20–80%. Aim To explore association between self-care behaviour, knowledge and cognition in patients with heart failure. Methods This is a secondary analysis of the baseline measures from the HF-Wii study with data from 605 patients, mean age 70 ± 12, 29% female, 30 % in New York Heart Association Class III-IV. Data on self-care was collected with European Self-care Behaviour Scale (EHFScBS) (possible range 0-100). Knowledge was collected with the Dutch HF Knowledge Scale (possible range 0-15 points). Cognition was assessed Montreal Cognitive Assessment (MoCA). Knowledge was dichotomised into low vs. high knowledge (cut off 13) and cognition into mild, moderate or severe cognitive problems vs. no or light cognitive problems. Results The total score on the EHFScBS was 64.6 ± 21.0 with 41% (N=245) of the patients performing good self-care (score &amp;gt; 70). The mean score on the Dutch HF Knowledge Scale was 12.3 ± 1.9 and 308 patients had high knowledge (score &amp;gt; 13). The majority of the patients (61%; N=371) had mild cognitive problems and 195 (32%) had no or light cognitive problems with a mean MOCA score of 24.4 ± 3.8. Self-care was significantly correlated to total knowledge (r = .23; p &amp;lt; .001), but it was not correlated to cognition. Furthermore, there was a positive correlation between total knowledge and cognition (r = .43; p &amp;lt;.001). Out of the 308 patients with high level of knowledge (&amp;gt;13), 130 had mild, moderate or severe cognitive problems. The other 178 patients with high knowledge had no or only light cognitive problems. Patients with high knowledge had a significantly higher score on the self-care behavior scale, independently of their cognitive function. In a multivariable logistic regression analysis, higher age [odds ratio (OR) 1.03; 95% confidence interval (CI) 1.02-1.06), better quality of life (OR .95; 95% CI .90 - .99) and higher levels of knowledge (OR 1.25; OR 1.13 – 1.38) were independently related to self-care. Conclusion HF knowledge and cognition are related in patients with heart failure, but only knowledge, not cognition, was independently related to self-care.

7 Cognitive Functioning Among Patients Undergoing CAR T-Cell Therapy

Objective:Chimeric antigen receptor (CAR) T-cell therapy is a novel treatment approach for refractory hematological malignancies. Risk factors for cognitive changes have been identified with CAR-T cell therapy, including severe cognitive problems due to neurotoxicity. Given the novelty of this treatment, research on this topic remains limited. Only one known study has examined cognitive performance following CAR T-cell therapy among patients diagnosed with non-Hodgkin’s lymphoma and observed a pattern of initial decline in executive functioning and visuospatial skills with improvement towards baseline one year following treatment. Additional research is needed to understand cognitive functioning in the context of CAR T-cell therapy. Our study presents preliminary descriptive longitudinal cognitive data among a small cohort of patients with mixed cancers undergoing CART cell therapy.Participants and Methods:Adult patients undergoing CAR T-cell therapy (N=16) completed the NIH-Toolbox core cognitive battery prior to treatment, and at 100-, 180-, and one-year post-treatment. Subtests of the Weschler Abbreviated Scale of Intelligence (WASI-II; block design, vocabulary) and the Wide Range Achievement Test (WRAT-5; word reading, math computation) were administered at baseline and one year follow up. Mean age of participants was 51.6 (SD = 14.4). Most patients had completed high school or more education (89.7%) identified as male (56.3%) and were white (75%). Diagnoses included lymphoblastic leukemia (n=2), diffuse large B-cell lymphoma (n=7), follicular lymphoma (n=3), mantle cell lymphoma (n=1), metastatic sarcoma (n=1), myxoid liposarcoma (n=1), and synovial sarcoma (n=1).Results:Mean cognitive scores (adjusted for age) were calculated. At baseline, mean cognitive performance was average across domains, except for inhibitory control, which was in the low average range. At day 100, mean cognitive performance showed the same pattern as baseline. At day 180, mean scores in all domains were within the average range. At one year, all scores were within the average range or higher, although only two participants have completed the one-year follow-up, as data collection is ongoing. One participant died due to neurotoxicity following treatment, thus did not complete follow-up evaluations.Conclusions:Overall, cognitive performances were broadly within normal limits in the sample and demonstrated relatively stable performance over time. Interestingly, baseline and day 100 mean inhibitory control was an area of relative weakness across participants, which is consistent with prior research. CAR T-cell therapy is reserved for refractory malignancies; thus, patients may have executive functioning deficits at baseline due to prior treatments. One patient died due to neurotoxicity. Overall, although severe cognitive changes and neurotoxicity have been observed as a risk of CAR T-cell therapy, this may be a distinct adverse event rather than the norm, as surviving patients in our sample remained cognitively stable following treatment. Although a unique and important population of study, our sample is limited due to its size. Results should be considered preliminary, and data collection is ongoing.

Assessment of Hearing Impairment in Sick Newborns: A Prospective Observational Study.

Undiagnosed neonatal hearing loss causes severe language, cognitive, and behavioral problems in children. Sick newborns who spend 48 hours in the neonatal intensive care unit (NICU) have a 10- to 20-fold increased risk of permanent hearing loss.The aim of this study is to identify hearing impairment in high-risk sick newborns who spend at least 48 hours in the NICU. The present prospective observational study was conducted at a single center.All sick neonates admitted to the NICU for a minimum of 48 hours at the JK Lon Hospital, Zanana Hospital, and Mahila Chikitsalaya, Sawai Man Singh (SMS) Medical College, Jaipur,Rajasthan, India, from June 2017 to May 2018 were considered eligible for the study.The primary outcome was the assessment of hearing loss of high-risk newborns using otoacoustic emissions at the time of discharge, six weeks of age, and automated auditory brainstem response (AABR) at three months of chronological age. The secondary outcome was to analyze the association of hearing loss with different risk factors in high-risk neonates. A total of 150 infants who had one or more risk factors were studied, 60 were female and 90 were male. No statistically significant difference in hearing loss was observed based on birth weight, sex, and gestational age.The firstdistortion-product otoacoustic emission(DPOAE) screening was done on infants at the time of discharge from the NICU. Eighty-three infants (55.33%) had "refer" on the first DPOAE and the remaining 67 (44.67%) were passed results at the time of discharge.At six weeks of life, on repeat screening with a second DPOAE test, 36% "refer"on the first screen had a"refer"result on the second DPOAE. However, 4.4% "pass" on the first screen turned out to be"refer"on the second screen. These 33 infants who had"refer"results on the second screen were subjected to testing.At 10 weeks of life, AABR wasperformedon 33 infants. Eleven infants out of 33 had sensorineural hearing loss (SNHL) on AABR. Hearing impairment with the DPOAE test was observed with risk factors neonatal hyperbilirubinemia (NHH), hypoxic ischemic encephalopathy (HIE), and very low birth weight (VLBW) and was statistically significant among all risk factors.But, no such association (between hearing impairment and risk factors) was observed with the AABR test. In our study, we found that the duration of mechanical ventilation in mean days 7.67±6.24 had statistically significant SNHL compared to the lesser duration of mechanical ventilation (p<0.001). Two-stage DPOAEdone prior to AABR is helpful in the early detection of hearing loss.

Effect of self-determination theory-based integrated creative art (SDTICA) program on older adults with mild cognitive impairment in nursing homes: Study protocol for a cluster randomised controlled trial

BackgroundThe cognitive benefits of early non-pharmacological approaches have been demonstrated in older adults with mild cognitive impairment (MCI). However, older adults living in nursing homes have more severe cognitive impairment problems and lower initiative and compliance to participate in complex interventions. Hence, it important to investigate more attractive and sustainable methods to prevent or delay cognitive decline. The present study adopts the self-determination theory (SDT) as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes in China and aims to evaluate its effects on cognitive function, mental health, and other health-related outcomes.MethodsThe study is a nursing home-based, cluster randomised controlled trial (RCT) that targets older adults (aged ≥ 60 years) with MCI in Fuzhou City, China. All nursing homes in the area covered by Fuzhou City are invited to participate. Eligible nursing homes are randomised to one of two groups: intervention group (receive a 14-week, 27-session intervention) and waitlist control group (receive the usual care). The SDT-based integrated creative art (SDTICA) program reasonably adopts the SDT as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes. The primary (global cognitive function and psychological indicator) and secondary (daily activity function, social function, and specific domains of cognitive function) outcomes will be measured at baseline, after the intervention, and during follow-up.DiscussionThis study aims to evaluate the effects of SDTICA program on neuropsychological outcomes in older adults with MCI and provide scientific evidence for art-based non-pharmacologic interventions in nursing homes, which may reduce dementia risk in older adults with MCI.Trial registrationThe trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022.

Interactions of genetic risks for autism and the broad autism phenotypes.

Common polygenic risk and de novo variants (DNVs) capture a small proportion of autism spectrum disorder (ASD) liability, and ASD phenotypic heterogeneity remains difficult to explain. Integrating multiple genetic factors contribute to clarifying the risk and clinical presentation of ASD. In our study, we investigated the individual and combined effects of polygenic risk, damaging DNVs (including those in ASD risk genes), and sex among 2,591 ASD simplex families in the Simons Simplex Collection. We also explored the interactions among these factors, along with the broad autism phenotypes of ASD probands and their unaffected siblings. Finally, we combined the effects of polygenic risk, damaging DNVs in ASD risk genes, and sex to explain the total liability of ASD phenotypic spectrum. Our findings revealed that both polygenic risk and damaging DNVs contribute to an increased risk for ASD, with females exhibiting higher genetic burdens than males. ASD probands that carry damaging DNVs in ASD risk genes showed reduced polygenic risk. The effects of polygenic risk and damaging DNVs on autism broad phenotypes were inconsistent; probands with higher polygenic risk exhibited improvement in some behaviors, such as adaptive/cognitive behaviors, while those with damaging DNVs exhibited more severe phenotypes. Siblings with higher polygenic risk and damaging DNVs tended to have higher scores on broader autism phenotypes. Females exhibited more severe cognitive and behavioral problems compared to males among both ASD probands and siblings. The combination of polygenic risk, damaging DNVs in ASD risk genes, and sex explained 1-4% of the total liability of adaptive/cognitive behavior measurements. Our study revealed that the risk for ASD and the autism broad phenotypes likely arises from a combination of common polygenic risk, damaging DNVs (including those in ASD risk genes), and sex.

Dementia in custody: A historical and forensic approach.

The constant ageing of the population extends to the population behind bars. We consider and summarise medical, ethical, legal and societal concerns raised when older adults with dementia are charged and put into custody.Dementia in custody is a relatively new concept in forensic science. When you take into account the adversarial nature of the judicial system and the hardship posed by correctional facilities, an older adult with severe cognitive problems will increases the complexity of the situation.The possibility of an octogenarian in cognitive decline being detained in police custody is less remote than it seemed half a century ago.

Social Network Characteristics and Correlations With Cognitive, Psychosocial, and Speech Function and Communication Participation for Adults With Multiple Sclerosis: A Pilot Study.

This cross-sectional observational pilot study investigated egocentric social networks for 10 paired sex- and age-matched adults with and without multiple sclerosis (MS). This study also investigated the relationship between social network measures and various disease factors associated with MS. The relationship between social network measures and communication participation restrictions was also examined. Participants completed a seven-item social network survey. Social network structure and composition were quantified. The network organization measures (structure analysis) included the total number of members (network size) and extent to which members are connected (network density). The measured characteristics of people around a participant (composition analysis) included the amount of kin relative to network size (proportion of kin), gender variation (gender diversity index), and age variation (standard deviation of age). Standard clinical neuropsychological, psychosocial, and speech metrics quantified processing speed, memory, depression, fatigue, and sentence intelligibility. Measures of communication participation and MS severity were also obtained. Matched-pairs tests indicated that the proportion of kin significantly differed between paired participants, whereas all other social network measures were similar. For participants with MS, correlation analyses indicated weak associations between proportion of kin and cognitive, psychosocial, and speech measures. However, strong correlations were found between social network size and processing speed, memory, fatigue, MS severity, and communication participation. Gender diversity index also strongly correlated with depression. Results from this pilot study highlight the importance of evaluating egocentric networks in the clinical management of MS, as maintaining nonkin friendships may be difficult for adults with MS making them vulnerable to social isolation. Furthermore, those with small and less diverse networks may experience more severe cognitive and psychosocial problems and limited communication participation.

Cognitive effort avoidance in veterans with suicide attempt histories

Suicide attempts (SA) are increasing in the United States, especially in veterans. Discovering individual cognitive features of the subset of suicide ideators who attempt suicide is critical. Cognitive theories attribute SA to facile schema-based negative interpretations of environmental events. Over-general autobiographical memory and facile solutions in problem solving tasks in SA survivors suggest that aversion to expending cognitive effort may be a neurobehavioral marker of SA risk. In veterans receiving care for mood disorder, we compared cognitive effort discounting and evidence-gathering in a beads task between veterans with (SAHx+; n = 26) versus without (SAHx-; n = 22) a history of SA. Groups did not differ in depressed mood or in a proxy metric of premorbid intelligence. Compared to SAHx- participants, SAHx+ participants self-reported significantly more severe cognitive problems in most domains, and also eschewed choice to earn higher monetary reward if earning it required a slightly increased working memory (WM) demand relative to an easy WM task. There was no group difference, however, in extent of evidence-gathering before declaring a conclusion in a beads task. These preliminary data suggest that aversion to expenditure of cognitive effort, potentially as a component of cognitive difficulties, may be a marker for SA risk.

Behavioral Changes and Cognitive Decline among Elderly

An individual’s behavior is impacted by a complex interaction of factors such as cognitive impairment, physical and mental health, past habits, personality, and environment. The cognitive decline means that your brain does not work as well as it used to. This study aimed to examine behavioral problems and cognitive decline among the elderly. The research information was gathered using multistage random sampling from various locations of Lucknow city (U.P). A total of 100 elderly were selected for conducting the present study comprising elderly belonging to different ages and both gender. A general information sheet was developed to collect the general information of the respondents. A Revised Memory and Behavioral Checklist scale developed by Teri, 1992, was used to assess the behavioral problems among the elderly. Females were found to have severe cognitive decline and behavioral problems compared to male respondents. Cooperation from family members and counseling sessions may prove beneficial in improving the overall cognitive health of female respondents.

Modeling Brain Overgrowth in Autism Using Human Pluripotent Stem Cells

16p11.2 copy number variation (CNV) is one of the most common genetic linkages of autism spectrum disorder (ASD). A large head size (referred to as macrocephaly) is common in 16p11.2 deletion syndrome, contributing to disproportionate enlargement in both gray and white matter volume. Individuals with ASD and macrocephaly have more severe behavioral and cognitive problems and are less responsive to standard therapeutic interventions, leading to poor prognoses relative to individuals with ASD and normal head circumferences.

Challenges faced by patients, relatives and clinicians in end-stage dementia decision-making: a qualitative study of swallowing problems

BackgroundDecision-making in end-stage dementia (ESD) is a complex process involving medical, social, legal and ethical issues. In ESD, the person suffers from severe cognitive problems leading to a loss of...

0120 Association Between Sleep Duration and Daytime Memory and Cognition Depends on Sleep Quality: Data from the 2017 Israel Social Survey

Abstract Introduction This study examines the relationship between sleep duration, sleep disturbance, and cognitive problems in a representative sample of the Israeli population. Methods 7,230 Israelis responded to an Israeli Bureau of Statistics population-based survey of households from the year 2017. All variables were self-reported. Outcome of interest was difficulty with memory/concentration (none, mild, or severe). Predictors included previous month sleep duration (&amp;lt;=5hrs, 6hrs, 7hrs [reference], 8hrs, or &amp;gt;=9hrs) and sleep disturbance (none [reference], mild [1/week], moderate [2–3/week], or severe [&amp;gt;3/week]). Covariates included age, sex, ethnic group, and financial status. Multinomial logistic regressions evaluated the relationships between variables, and post-hoc testing identified relationships within specific subgroups. Results 72.9% denied cognitive problems, 22.2% reported mild problems, and 4.9% severe problems. In adjusted analyses, Sleep &amp;lt;=5hrs and &amp;gt;=9hrs were associated with mild (RRR=1.39, p&amp;lt;0.0005), (RRR=1.46, p=0.004) and severe (RRR=2.75, p&amp;lt;0.0005), (RRR=3.24, p&amp;lt;0.0005) cognitive problems, respectively. Mild, moderate, and severe sleep difficulties were associated with mild cognitive problems (RRR=2.09, p&amp;lt;0.0005), (RRR=2.22, p&amp;lt;0.0005), (RRR=2.44, p&amp;lt;0.0005), and severe cognitive problems (RRR=1.77, p=0.001), (RRR=3.04, p&amp;lt;0.0005), (RRR=4.22, p&amp;lt;0.0005), respectively. There was an interaction between sleep duration and sleep difficulties (p&amp;lt;0.05). Among those denying sleep difficulties, only &amp;gt;=9hrs of sleep was associated with cognitive problems. Among those with mild, moderate, and severe sleep difficulties, both short and long sleep were associated with cognitive problems. Conclusion In an Israeli population sample, both sleep duration and quality were associated with cognitive problems. Among those with sleep difficulties, short and long sleep duration were associated with cognitive problems, but among those denying sleep difficulties, only long sleep was associated with cognitive problems. These results suggest that the impact of sleep loss on real-world cognition may also rely on the presence of poor sleep quality. Support Dr. Grandner is supported by R01MD011600

SARC-F in hospitalized, geriatric medical patients – Feasibility, prevalence of risk of sarcopenia, and characteristics of the risk group, including one-year follow-up

SARC-F is an interview-based screening-tool recommended to rapidly screen for risk of sarcopenia - the loss of muscle mass and strength. Not previously investigated, this observational study aimed to assess the feasibility of the SARC-F screening tool in Danish geriatric medical patients, estimate the prevalence of risk, and investigate associations to predefined variables. This was an observational cohort study with a one-year follow-up. All non-isolated patients ≥65 years, understanding Danish and admitted to a Danish geriatric medical ward in the capital region of Denmark, were recruited. If readmitted during the study period, they were not included again. The following data were collected upon recruitment; demographics, nutritional risk screening (NRS-2002), BMI, calf-circumference, Barthel-index, health-related Quality of life (QoL), hand-grip strength (HGS), and length of hospital admission. Additionally, the one-year follow-up included mortality, admission(s) to hospital, and visits to the emergency-room. From September 2017 to February 2018, 461 patients were admitted, 377 eligible, and 301 included. Study feasibility was 80%, and estimated feasibility if implemented in daily clinical practice was 85%, as some patients had to be excluded from screening due to cognitive impairment. The prevalence of the risk of sarcopenia upon admission for participants were 64.5%. Being at risk were characterized by significantly lower HGS, Barthel-index, and QoL, as well as longer admissions (men only), and one-year mortality (female only) (P≤0.05). Use of SARC-F is feasible in a geriatric setting, but only in older adults without severe cognitive problems. Risk of sarcopenia among geriatric patients ≥65 years is high, and the risk group is characterized by lower strength, functional- and QoL measurements, longer hospitalization (men only), and increased mortality (women only).

PREPL Deficiency: A Homozygous Splice Site PREPL Mutation in a Patient With Congenital Myasthenic Syndrome and Absence of Ovaries and Hypoplasia of Uterus.

Prolyl endopeptidase-like (PREPL) deficiency (MIM 616224) is a very rare congenital disorder characterized by neonatal hypotonia and feeding difficulties, ptosis, neuromuscular symptoms, cognitive impairments, growth hormone deficiency, short stature, and hypergonadotropic hypogonadism. This syndrome is an autosomal recessive disease resulting from mutations in the PREPL gene. Previous reports have associated PREPL deficiency with only one nucleotide substitution, the deletion of four nucleotides, and eight small microdeletions in the PREPL gene In this study, we used whole exome sequencing (WES) to identify a novel homozygous splicing mutation (c.616 + 1G > T) in a 14-year-old Chinese girl with PREPL deficiency. Sequencing of the RT-PCR products from the patient’s blood sample revealed that the c.616 + 1G > T variant disrupted normal splicing in intron 4 leading to an aberrant inclusion of 43 nucleotides in intron, a frameshift, and premature termination codon. Our patient exhibited several of the common phenotypes, including severe neonatal hypotonia, growth impairment and cognitive problems. However, we also observed several unusual phenotypic characteristics: absence of the ovaries, hypoplasia of the uterus, microcephaly and a short neck in patient is alsoobserved. These results provide further evidence for the involvement of PREPL development of the ovaries and uterus. Our findings may provide further insight into the relationship between the genotype and phenotype in collagen-associated diseases and improve the clinical diagnosis of Prolyl endopeptidase-like deficiency.

The Effect of Empowerment Program for Nurses Regarding Management of Children with Phenylketonuria

Context: Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. If PKU did not diagnose early in life or the affected children with PKU do not be compliant with the treatment regimen (food), it leads to severe cognitive or behavioral problems, seizures, and autistic symptoms.&#x0D; Aim: The current study aimed to evaluate the effect of empowerment program on nurses' management of children with phenylketonuria.&#x0D; Methods: Quasi-experimental research (one group pre/post-test) design was used to conduct this study. The study was carried out in the hereditary unit, and hereditary outpatient clinics at Ain Shams Specialized Hospital for children affiliated to Ain shams University. A convenient sample of all available nurses working in the previously mentioned study settings (80 male and female bedside nurses) from the beginning of May 2018 to the end of October 2018. Two tools were utilized for data collection for the current study. They are the structured interview questionnaire to assess the nurses' knowledge regarding the management of children with phenylketonuria and the nurses’ performance observation checklists regarding nursing care provided for children with phenylketonuria&#x0D; Results: nurses' knowledge regarding phenylketonuria was unsatisfactory before the empowerment program, while there is a statistically significant improvement between pre and post empowerment program implementation. Nurses' practice regarding phenylketonuria was incompetent before the empowerment program compared to post empowerment program. There is a positive statistical relationship between nurses' knowledge and practice post-program implementation.&#x0D; Conclusion: The study revealed that the empowerment program had a positive effect on the nurses' knowledge and practice towards the management of children with phenylketonuria. The current study recommended continuous education and training sessions about the management of children with phenylketonuria that should be provided to upgrade the knowledge and improve the practice of nurses caring for PKU children. Availability and accessibility of printed guidelines, posters, and simple handouts regarding the management of children with phenylketonuria.

Group cognitive rehabilitation to reduce the psychological impact of multiple sclerosis on quality of life: the CRAMMS RCT.

People with multiple sclerosis have problems with memory and attention. The effectiveness of cognitive rehabilitation has not been established. The objectives were to assess the clinical effectiveness and cost-effectiveness of a cognitive rehabilitation programme for people with multiple sclerosis. This was a multicentre, randomised controlled trial in which participants were randomised in a ratio of 6 : 5 to receive cognitive rehabilitation plus usual care or usual care alone. Participants were assessed at 6 and 12 months after randomisation. The trial was set in hospital neurology clinics and community services. Participants were people with multiple sclerosis who had cognitive problems, were aged 18-69 years, could travel to attend group sessions and gave informed consent. The intervention was a group cognitive rehabilitation programme delivered weekly by an assistant psychologist to between four and six participants for 10 weeks. The primary outcome was the Multiple Sclerosis Impact Scale - Psychological subscale at 12 months. Secondary outcomes included results from the Everyday Memory Questionnaire, the 30-Item General Health Questionnaire, the EuroQol-5 Dimensions, five-level version and a service use questionnaire from participants, and the Everyday Memory Questionnaire - relative version and the Modified Carer Strain Index from a relative or friend of the participant. Of the 449 participants randomised, 245 were allocated to cognitive rehabilitation (intervention group) and 204 were allocated to usual care (control group). Of these, 214 in the intervention group and 173 in the control group were included in the primary analysis. There was no clinically important difference in the Multiple Sclerosis Impact Scale - Psychological subscale score between the two groups at the 12-month follow-up (adjusted difference in means -0.6, 95% confidence interval -1.5 to 0.3; p = 0.20). There were no important differences between the groups in relation to cognitive abilities, fatigue, employment, or carer strain at follow-up. However, there were differences, although small, between the groups in the Multiple Sclerosis Impact Scale - Psychological subscale score at 6 months (adjusted difference in means -0.9, 95% confidence interval -1.7 to -0.1; p = 0.03) and in everyday memory on the Everyday Memory Questionnaire as reported by participants at 6 (adjusted difference in means -5.3, 95% confidence interval -8.7 to -1.9) and 12 months (adjusted difference in means -4.4, 95% confidence interval -7.8 to -0.9) and by relatives at 6 (adjusted difference in means -5.4, 95% confidence interval -9.1 to -1.7) and 12 months (adjusted difference in means -5.5, 95% confidence interval -9.6 to -1.5) in favour of the cognitive rehabilitation group. There were also differences in mood on the 30-Item General Health Questionnaire at 6 (adjusted difference in means -3.4, 95% confidence interval -5.9 to -0.8) and 12 months (adjusted difference in means -3.4, 95% confidence interval -6.2 to -0.6) in favour of the cognitive rehabilitation group. A qualitative analysis indicated perceived benefits of the intervention. There was no evidence of a difference in costs (adjusted difference in means -£574.93, 95% confidence interval -£1878.93 to £729.07) or quality-adjusted life-year gain (adjusted difference in means 0.00, 95% confidence interval -0.02 to 0.02). No safety concerns were raised and no deaths were reported. The trial included a sample of participants who had relatively severe cognitive problems in daily life. The trial was not powered to perform subgroup analyses. Participants could not be blinded to treatment allocation. This cognitive rehabilitation programme had no long-term benefits on quality of life for people with multiple sclerosis. Future research should evaluate the selection of those who may benefit from cognitive rehabilitation. Current Controlled Trials ISRCTN09697576. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 4. See the National Institute for Health Research Journals Library website for further project information.