Comorbidity Profile of Dementia Patients in Primary Care: Are They Sicker?

OBJECTIVES: To compare the medical comorbidity of older patients with and without dementia in primary care. DESIGN: Cross-sectional study. SETTING: Wishard Health Services, which includes a university-affiliated, urban public hospital and seven community-based primary care practice centers in Indianapolis. PARTICIPANTS: Three thousand thirteen patients aged 65 and older attending seven primary care centers in Indianapolis, Indiana. MEASUREMENTS: An expert panel diagnosed dementia using International Classification of Diseases, 10th Revision, criteria. Comorbidity was assessed using 10 physician-diagnosed chronic comorbid conditions and the Chronic Disease Score (CDS). RESULTS: Patients with dementia attending primary care have on average 2.4 chronic conditions and receive 5.1 medications. Approximately 50% of dementia patients in this setting are exposed to at least one anticholinergic medication, and 20% are prescribed at least one psychotropic medication. After adjusting for patients' age, race, and sex, patients with and without dementia have a similar level of comorbidity (mean number of chronic medical conditions, 2.4 vs 2.3, P=.66; average CDS, 5.8 vs 6.2, P=.83). CONCLUSION: Multiple medical comorbid conditions are common in older adults with and without dementia in primary care. Despite their cholinergic deficit, a substantial proportion of patients with dementia are exposed to anticholinergic medications. Models of care that incorporate this medical complexity are needed to improve the treatment of dementia in primary care.     

Copy number variations in neurodevelopmental disorders

Common neurodevelopmental disorders (including autism, speech and language delay, schizophrenia, epilepsy and intellectual disability) have complex aetiology, which is predominantly genomic, but also environmental in origin. They share a paradox, in that high heritability is matched by lowered fecundity, placing them under negative genetic selection. This implicates variants of recent origin, such as de novo mutations or common, very low-risk polymorphisms that escape negative selection. High or moderate risk variants have been discovered by chromosome analysis, genome sequencing and copy number variant (CNV) detection, including a 3Mb deletion causing 22q11.2 deletion syndrome (Velo-Cardio-Facial Syndrome) that has penetrance of up to 50% for schizophrenia. More recently, rare, recurrent and often de novo pathogenic CNVs, including deletions at NRXN1, 1q21.2, 15q11.2 and 15q13.3, 16p11.2 and duplications at VIPR2 and 16p13.11, have also been discovered. These have several unique features that differentiate them from Mendelian disease mutations in that they have incomplete penetrance, with moderate-to-high odds ratios for risk, and show diagnostic pleiotropy, increasing risk across the neurodevelopmental disorder spectrum. Some are also syndromic, with characteristic features such as facial dysmorphology, and other specific risks such as aortic dissection or obesity, implying that they might be better classified as distinct diagnoses. The discovery of pathogenic CNVs provide new opportunities for translation leading to patent benefit, including improvements in clinical genetic diagnosis and genetic counselling, the possibility of clinician decision-making tools for risk prediction, and the identification of drug targets and implementation of personalised medicine using stratification by genotype.     

A strabismus susceptibility locus on chromosome 7p

Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes.     

Molecular epidemiology of dual HIV-1/HIV-2 seropositive adults from Senegal,West Africa

Dual infection with HIV-1 and HIV-2 can occur in locales where these viruses co-circulate, most commonly in West Africa. Although dual seropositivity is common in this region, the true rate of dual infection remains unclear. In addition, whether unique HIV-1 subtypes are circulating in dually infected individuals is unknown. A cohort of 47 HIV-1 and HIV-2 dually seropositive individuals from Senegal, West Africa was screened for the presence of HIV-1 and HIV-2 gag and env PBMC viral DNA sequences using PCR. Of the 47 dual HIV-1/HIV-2 seropositive individuals tested, 19 (40.4%) had infection with both HIV-1 and HIV-2 confirmed by genetic sequence analysis, whereas only HIV-1 or HIV-2 was confirmed in 17 (36.2%) or 9 (19.1%), respectively. The majority of HIV-1 subtypes found were CRF-02 and A, although subtypes D, C, G, J and B were also found, reflecting the subtypes known to be circulating in Senegal. There was no significant difference in HIV-1 subtype distribution between individuals with confirmed dual infection and patients in this study with dual seropositivity but lacking HIV-2, or with HIV-1 infected patients within the general population in Senegal, although the study was underpowered to detect anything but large differences. The prevalence of HIV-1/HIV-2 dual infection appears to be significantly less than that of dually seropositive individuals and this likely reflects cross-reactive serology. The common HIV-1 subtypes prevalent in West Africa (CRF-02 and subtype A) have a similar distribution to those found in our cohort of dually infected and dually seropositive subjects.     

Coping and Management Techniques Used by Chronic Low Back Pain Patients Receiving Treatment From Chiropractors

ObjectivesThe purpose of this study was to describe coping strategies (eg, mechanisms, including self-treatment) that a person uses to reduce pain and its impact on functioning as reported by patients with chronic low back pain who were seen by doctors of chiropractic and how these coping strategies vary by patient characteristics.MethodsData were collected from a national sample of US chiropractic patients recruited from chiropractic practices in 6 states from major geographical regions of the United States using a multistage stratified sampling strategy. Reports of coping behaviors used to manage pain during the past 6 months were used to create counts across 6 domains: cognitive, self-care, environmental, medical care, social activities, and work. Exploratory analyses examined counts in domains and frequencies of individual items by levels of patient characteristics.ResultsA total of 1677 respondents with chronic low back pain reported using an average of 9 coping behaviors in the prior 6 months. Use of more types of behaviors were reported among those with more severe back pain, who rated their health as fair or poor and who had daily occurrences of pain. Exercise was more frequent among the healthy and those with less pain. Female respondents tended to report using more coping behaviors than men, and Hispanics more than non-Hispanics.ConclusionPersons with chronic back pain were proactive in their coping strategies and frequently used self-care coping strategies like those provided by chiropractors in patient education. In alignment with patients’ beliefs that their condition was chronic and lifelong, many patients attempted a wide range of coping strategies to relieve their pain.     

Detecting subject-specific activations using fuzzy clustering

Inter-subject variability in evoked brain responses is attracting attention because it may reflect important variability in structure-function relationships over subjects. This variability could be a signature of degenerate (many-to-one) structure-function mappings in normal subjects or reflect changes that are disclosed by brain damage. In this paper, we describe a non-iterative fuzzy clustering algorithm (FCP: fuzzy clustering with fixed prototypes) for characterizing inter-subject variability in between-subject or second-level analyses of fMRI data. The approach identifies the contribution of each subject to response profiles in voxels surviving a classical F-statistic criterion. The output identifies subjects who drive activation in specific cortical regions (local effects) or in voxels distributed across neural systems (global effects). The sensitivity of the approach was assessed in 38 normal subjects performing an overt naming task. FCP revealed that several subjects had either abnormally high or abnormally low responses. FCP may be particularly useful for characterizing outlier responses in rare patients or heterogeneous populations. In these cases, atypical activations may not be detected by standard tests, under parametric assumptions. The advantage of using FCP is that it searches all voxels systematically and can identify atypical activation patterns in a quantitative and unsupervised manner.     

Breaking Down Silos: Mapping Growth of Cross‐Disciplinary Collaboration in a Translational Science Initiative

The importance of transdisciplinary collaboration is growing, though not much is known about how to measure collaboration patterns. The purpose of this paper is to present multiple ways of mapping and evaluating the growth of cross‐disciplinary partnerships over time. Social network analysis was used to examine the impact of a Clinical and Translational Science Award (CTSA) on collaboration patterns. Grant submissions from 2007 through 2010 and publications from 2007 through 2011 of Institute of Clinical and Translational Sciences (ICTS) members were examined. A Cohort Model examining the first‐year ICTS members demonstrated an overall increase in collaborations on grants and publications, as well as an increase in cross‐discipline collaboration as compared to within‐discipline. A Growth Model that included additional members over time demonstrated the same pattern for grant submissions, but a decrease in cross‐discipline collaboration as compared to within‐discipline collaboration for publications. ICTS members generally became more cross‐disciplinary in their collaborations during the CTSA. The exception of publications for the Growth Model may be due to the time lag between funding and publication, as well as pressure for younger scientists to publish in their own fields. Network analysis serves as a valuable tool for evaluating changes in scientific collaboration.     

Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health

ABSTRACT

Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new ‘generation’ of potentially beneficial microbes to have been recognized are members of the genus Eubacterium, who form a part of the core human gut microbiome. The genus consists of phylogenetically, and quite frequently phenotypically, diverse species, making Eubacterium a taxonomically unique and challenging genus. Several members of the genus produce butyrate, which plays a critical role in energy homeostasis, colonic motility, immunomodulation and suppression of inflammation in the gut. Eubacterium spp. also carry out bile acid and cholesterol transformations in the gut, thereby contributing to their homeostasis. Gut dysbiosis and a consequently modified representation of Eubacterium spp. in the gut, have been linked with various human disease states. This review provides an overview of Eubacterium species from a phylogenetic perspective, describes how they alter with diet and age and summarizes its association with the human gut and various health conditions.