Project description:To review how disability can develop in older adults with critical illness and to explore ways to reduce long-term disability following critical illness.We searched PubMed, CINAHL, Web of Science and Google Scholar for studies reporting disability outcomes (i.e., activities of daily living, instrumental activities of daily living, and mobility activities) and/or cognitive outcomes among patients treated in an ICU who were 65 years or older. We also reviewed the bibliographies of relevant citations to identify additional citations.We identified 19 studies evaluating disability outcomes in critically ill patients who were 65 years and older.Descriptive epidemiologic data on disability after critical illness.Newly acquired disability in activities of daily living, instrumental activities of daily living, and mobility activities was commonplace among older adults who survived a critical illness. Incident dementia and less severe cognitive impairment were also highly prevalent. Factors related to the acute critical illness, ICU practices, such as heavy sedation, physical restraints, and immobility, as well as aging physiology, and coexisting geriatric conditions can combine to result in these poor outcomes.Older adults who survive critical illness have physical and cognitive declines resulting in disability at greater rates than hospitalized, noncritically ill and community dwelling older adults. Interventions derived from widely available geriatric care models in use outside of the ICU, which address modifiable risk factors including immobility and delirium, are associated with improved functional and cognitive outcomes and can be used to complement ICU-focused models such as the ABCDEs.
Project description:Intellectual disability is the most common developmental disorder characterized by a congenital limitation in intellectual functioning and adaptive behavior. It often co-occurs with other mental conditions like attention deficit/hyperactivity disorder and autism spectrum disorder, and can be part of a malformation syndrome that affects other organs. Considering the heterogeneity of its causes (environmental and genetic), its frequency worldwide varies greatly. This review focuses on known genes underlying (syndromic and non-syndromic) intellectual disability, it provides a succinct analysis of their Gene Ontology, and it suggests the use of transcriptional profiling for the prioritization of candidate genes.
Project description:Limitations in essential daily activities are common among older adults after stroke, but little is known about restrictions in their ability to participate in valued social activities. We sought to broaden our understanding of disability after stroke by characterizing poststroke participation restrictions and investigating the extent to which they are accounted for by differences in physical and cognitive capacity, aphasia/dysarthria, depressive, and anxiety symptoms.Data from the 2011 National Health and Aging Trends Study (NHATS) were used to identify 892 self-reported stroke survivors aged?65 years. One-to-one propensity matching was performed on demographics and comorbidities to create a matched sample. Participation restrictions were defined as reductions/absence in social activities valued by respondents because of their health or functioning. Physical and cognitive capacity, depressive and anxiety symptoms were measured by validated scales and aphasia/dysarthria by a single question. Comparisons using survey-weighted ?2 tests and logistic regression were made.Stroke survivors had more participation restrictions (32.8% versus 23.5%; odds ratio, 1.59; 95% confidence interval, 1.28-1.95; P<0.01) than controls. Differences between stroke survivors and controls in any participation restriction and several components (attending religious service, clubs/classes, and going out for enjoyment) were eliminated after adjusting for physical capacity. Depressive and anxiety symptoms and aphasia/dysarthria were independent predictors of participation restrictions.Stroke survivors have more participation restrictions than can be accounted for by sociodemographic profiles and comorbidity burden. Future work aimed at improving physical capacity, reducing depressive and anxiety symptoms, and improving aphasia/dysarthria has potential to enhance participation.
Project description:The point prevalence methodology is a valuable epidemiological study design that can optimize patient enrollment, prospectively gather individual-level data, and measure practice variability across a large number of geographic regions and healthcare settings. The objective of this article is to review the design, implementation, and analysis of recent point prevalence studies investigating the global epidemiology of pediatric critical illness.Literature review and primary datasets.Multicenter, international point prevalence studies performed in PICUs since 2007.Study topic, number of sites, number of study days, patients screened, prevalence of disease, use of specified therapies, and outcomes.Since 2007, five-point prevalence studies have been performed on acute lung injury, neurologic disease, thromboprophylaxis, fluid resuscitation, and sepsis in PICUs. These studies were performed in 59-120 sites in 7-28 countries. All studies accounted for seasonal variation in pediatric disease by collecting data over multiple study days. Studies screened up to 6,317 patients and reported data on prevalence and therapeutic variability. Three studies also reported short-term outcomes, a valuable but atypical data element in point prevalence studies. Using these five studies as examples, the advantages and disadvantages and approach to designing, implementing, and analyzing point prevalence studies are reviewed.Point prevalence studies in pediatric critical care can efficiently provide valuable insight on the global epidemiology of disease and practice patterns for critically ill children.
Project description:OBJECTIVES:We test a comprehensive model of disability in older stroke survivors and determine the relative contribution of neighborhood, economic, psychological, and medical factors to disability. METHOD:The sample consisted of 728 stroke survivors from the National Health and Aging Trends Study (NHATS), who were 65 years and older living in community settings or residential care. Confirmatory factor analysis and structural equation modeling were used to test relationships between neighborhood, socioeconomic, psychological, and medical factors, and disability. RESULTS:Economic and medical context were associated with disability directly and indirectly through physical impairment. Neighborhood context was associated with disability, but was only marginally statistically significant ( p = .05). The effect of economic and neighborhood factors was small compared with that of medical factors. DISCUSSION:Neighborhood and economic factors account for a portion of the variance in disability among older stroke survivors beyond that of medical factors.
Project description:Cytomegalovirus (CMV) reactivation has been described in adults with critical illness caused by diverse etiologies, especially severe sepsis, and observational studies have linked CMV reactivation with worse clinical outcomes in this setting. In this study, we review observational clinical data linking development of CMV reactivation with worse outcomes in patients in the intensive care unit, discuss potential biologically plausible mechanisms for a causal association, and summarize results of initial interventional trials that examined the effects of CMV prevention. These data, taken together, highlight the need for a randomized, placebo-controlled efficacy trial (1) to definitively determine whether prevention of CMV reactivation improves clinical outcomes of patients with critical illness and (2) to define the underlying mechanism(s).
Project description:IntroductionThere is scarcity of data on children with disabilities living in low-and-middle-income countries, including Uganda. This study describes disability prevalence and explores factors associated with different disability categories. It highlights the value of using a standardized, easy-to-use tool to determine disability in children and contextualizing disability in children in light of their developmental needs.MethodsA cross-sectional study was conducted between September 2018-January 2019 at the Iganga-Mayuge Health and Demographic Surveillance Site in Uganda. Respondents were caregivers of children between 5-17 years and were administered an in-depth Child Functioning Module (CFM). The outcome variable, disability, was defined as an ordered categorical variable with three categories-mild, moderate, and severe. Generalized ordered logit model was applied to explore factors associated with disability categories.ResultsOut of 1,842 caregivers approached for the study, 1,439 (response: 78.1%) agreed to participate in the study. Out of these 1,439, some level of disability was reported by 67.89% (n = 977) of caregivers. Of these 977 children with disability, 48.01% (n = 692) had mild disability and 15.84% (n = 228) had moderate disability, while 3.96% (n = 57) had severe disability. The mean (SD) score for mild disability was 2.22±1.17, with a median of 2. The mean and median for moderate disability was 5.26±3.28 and 4 (IQR:3-6), and for severe disability was 14.23±9.51 and 12 (IQR:6-22). The most common disabilities reported were depression (54.83%) and anxiety (50.87%). Statistically significant association was found for completion of immunization status and school enrollment when controlled for a child's age, sex, having a primary caregiver, age of mother at child's birth, family system, family size and household wealth quintile.ConclusionThis study suggests association between incomplete immunization status and school enrollment for children with disability. These are areas for further exploration to ensure inclusive health and inclusive education of children with disabilities in Uganda.
Project description:Background and objectiveUsage of data from electronic health records (EHRs) in clinical research is increasing, but there is little empirical knowledge of the data needed to support multiple types of research these sources support. This study seeks to characterize the types and patterns of data usage from EHRs for clinical research.Materials and methodsWe analyzed the data requirements of over 100 retrospective studies by mapping the selection criteria and study variables to data elements of two standard data dictionaries, one from the healthcare domain and the other from the clinical research domain. We also contacted study authors to validate our results.ResultsThe majority of variables mapped to one or to both of the two dictionaries. Studies used an average of 4.46 (range 1-12) data element types in the selection criteria and 6.44 (range 1-15) in the study variables. The most frequently used items (e.g., procedure, condition, medication) are often available in coded form in EHRs. Study criteria were frequently complex, with 49 of 104 studies involving relationships between data elements and 22 of the studies using aggregate operations for data variables. Author responses supported these findings.Discussion and conclusionThe high proportion of mapped data elements demonstrates the significant potential for clinical data warehousing to facilitate clinical research. Unmapped data elements illustrate the difficulty in developing a complete data dictionary.
Project description:Current understanding of environmental cross-talk with genetic makeup is found to be mediated through an epigenetic interface which is associated with prominent reversible and heritable changes at gene expression level. Recent emergence of epigenetic modulation in shaping the genetic information has become a key regulatory factor in answering the underlying complexities associated with several mental disorders. A comprehensive understanding of the pertinent changes in the epigenetic makeup of suicide phenotype exhibits a characteristic signature with the possibility of using it as a biomarker to help predict the risk factors associated with suicide. Within the scope of this current review, the most sought after epigenetic changes of DNA methylation and histone modification are thoroughly scrutinized to understand their close functional association with the broad spectrum of suicide phenotype.
Project description:The binding of thrombomodulin (TM) to exosite-1 and the binding of Na(+) to 225-loop allosterically modulate the catalytic activity and substrate specificity of thrombin. To determine whether the conformation of these two cofactor-binding loops are energetically linked to each other and to the active site, we rationally designed two thrombin mutants in which either the 70-80 loop of exosite-1 or the 225-loop of the Na(+)-binding site was stabilized by an engineered disulfide bond. This was possible by replacing two residues, Arg-67 and Ile-82, in the first mutant and two residues, Glu-217 and Lys-224, in the second mutant with Cys residues. These mutants were expressed in mammalian cells as monomeric molecules, purified to homogeneity and characterized with respect to their ability to bind TM and Na(+) by kinetic and direct binding approaches. The Cys-67/Cys-82 mutant did not bind TM and exhibited a normal amidolytic activity, however, the activity of Cys-217/Cys-224 was dramatically impaired, though TM interacted with this mutant with >20-fold elevated K(D) to partially restore its activity. Both mutants exhibited approximately 2-3-fold higher K(D) for interaction with Na(+), and neither mutant clotted fibrinogen or activated protein C in the presence of TM. Both mutants interacted with heparin with a normal affinity. These results suggest that, while exosite-2 of thrombin is an independent cofactor binding-site, both Na(+)-binding and exosite-1 are energetically linked. Further studies with the fluorescein labeled Cys-195 mutant of thrombin revealed that the catalytic residue of thrombin is modulated by Na(+), but TM has no effect on the conformation of this residue.