Helping family doctors detect vulnerable caregivers after an emergency department visit for an elderly relative: results of a longitudinal study

BACKGROUND: Family doctors have been ascribed a role in monitoring patients and their informal caregivers. Little is known about the factors that might alert physicians to changing circumstances or needs of the caregivers. The study objective was to examine changes in family caregivers' quality of life following an emergency department (ED) visit by an older community-dwelling relative that might cue doctors to subsequent caregiver distress. METHODS: A longitudinal study with follow-up at 1- and 4-months was conducted in the EDs of 4 hospitals in Montreal, Canada. Caregivers reported on demographics and quality of life (SF-36). Patients reported on demographics and functional disability. Multiple linear regression for repeated measures was used to evaluate changes in caregiver quality of life and factors related to these changes. RESULTS: 159 caregivers (60.5 yrs ± 15.8%; 73.0% female), including 68 (42.8%) spouses, 60 (37.7%) adult children, and 31 (19.5%) other relatives participated. Following an initial ED visit by older relatives, caregiver general health and physical functioning declined over time, while mental health status improved. Compared to the other relative caregiver group, spouses were at increased risk for decline in general health, mental health, and physical functioning at 1 month, while adult children were at increased risk for decline in physical health at 1 month. CONCLUSION: Spouses were most at risk for decline in quality of life. Primary care physicians who become aware of an ED visit by an elderly person may be alerted to possible subsequent deterioration in family caregivers, especially spouses

Socio-demographic and clinical characteristics of re-presentation to an Australian inner-city emergency department: implications for service delivery

BACKGROUND: People who have complex health care needs frequently access emergency departments for treatment of acute illness and injury. In particular, evidence suggests that those who are homeless, or suffer mental illness, or have a history of substance misuse, are often repeat users of emergency departments. The aim of this study was to describe the socio-demographic and clinical characteristics of emergency department re-presentations. Re-presentation was defined as a return visit to the same emergency department within 28 days of discharge from hospital. METHODS: A retrospective cohort study was conducted of emergency department presentations occurring over a 24-month period to an Australian inner-city hospital. Characteristics were examined for their influence on the binary outcome of re-presentation within 28 days of discharge using logistic regression with the variable patient fitted as a random effect. RESULTS: From 64,147 presentations to the emergency department the re-presentation rate was 18.0% (n = 11,559) of visits and 14.4% (5,894/40,942) of all patients. Median time to re-presentation was 6 days, with more than half occurring within one week of discharge (60.8%; n = 6,873), and more than three-quarters within two weeks (80.9%; n = 9,151). The odds of re-presentation increased three-fold for people who were homeless compared to those living in stable accommodation (adjusted OR 3.09; 95% CI, 2.83 to 3.36). Similarly, the odds of re-presentation were significantly higher for patients receiving a government pension compared to those who did not (adjusted OR 1.73; 95% CI, 1.63 to 1.84), patients who left part-way through treatment compared to those who completed treatment and were discharged home (adjusted OR 1.64; 95% CI, 1.36 to 1.99), and those discharged to a residential-care facility compared to those who were discharged home (adjusted OR 1.46: 95% CI, 1.03 to 2.06). CONCLUSION: Emergency department re-presentation rates cluster around one week after discharge and rapidly decrease thereafter. Housing status and being a recipient of a government pension are the most significant risk factors. Early identification and appropriate referrals for those patients who are at risk of emergency department re-presentation will assist in the development of targeted strategies to improve health service delivery to this vulnerable group

Delirium risk screening and haloperidol prophylaxis program in hip fracture patients is a helpful tool in identifying high-risk patients, but does not reduce the incidence of delirium

Background: Delirium in patients with hip fractures lead to higher morbidity and mortality. Prevention in high-risk patients by prescribing low dose haloperidol is currently under investigation. Methods. This prospective cohort surveillance assessed hip fracture patients for risk of developing a delirium with the Risk Model for Delirium (RD) score. High-risk patients (score ≥5 points) were treated with a prophylactic low-dose of haloperidol according to hospital protocol. Primary outcome was delirium incidence. Secondary outcomes were differences between high- and low-risk patients in delirium, length of stay (LOS), return to pre-fracture living situation and mortality. Logistic regression analysis was performed with age, ASA-classification, known dementia, having a partner, type of fracture, institutional residence and psychotropic drug use as possible confounders. Results: 445 hip fracture patients aged 65 years and older were admitted from January 2008 to December 2009. The RD-score was completed in 378 patients, 173 (45.8%) high-risk patients were treated with prophylactic medication. Sensitivity was 71.6%, specificity 63.8% and the negative predictive value (NPV) of a score < 5 was 85.9%. Delirium incidence (27.0%) was not significantly different compared to 2007 (27.8%) 2006 (23.9%) and 2005 (29.0%) prior to implementation of the RD- protocol. Logistic regression analysis showed that high-risk patients did have a significant higher delirium incidence (42.2% vs. 14.1%, OR 4.1, CI 2.43-7.02). They were more likely to be residing at an alternative living situation after 3 months (62.3% vs. 17.0%, OR 6.57, CI 3.23-13.37) and less likely to be discharged from hospital before 10 days (34.9% vs. 55.9%, OR 1.63, CI 1.03-2.59). Significant independent risk factors for a delirium were a RD-score 5 (OR 4.13, CI 2.43-7.02), male gender (OR 1.93, CI 0.99-1.07) and age (OR 1.03, CI 0.99-1.07). Conclusions: Introducing the delirium prevention protocol did not reduce delirium incidence. The RD-score did identify patients with a high risk to develop a delirium. This high-risk group had a longer LOS and returned to pre-fracture living situation less often. The NPV of a score < 5 was high, as it should be for a screening instrument. Concluding, the RD-score is a useful tool to identify patients with poorer outcome

Saccharomyces cerevisiae: Population Divergence and Resistance to Oxidative Stress in Clinical, Domesticated and Wild Isolates

BACKGROUND: Saccharomyces cerevisiae has been associated with human life for millennia in the brewery and bakery. Recently it has been recognized as an emerging opportunistic pathogen. To study the evolutionary history of S. cerevisiae, the origin of clinical isolates and the importance of a virulence-associated trait, population genetics and phenotypic assays have been applied to an ecologically diverse set of 103 strains isolated from clinics, breweries, vineyards, fruits, soil, commercial supplements and insect guts. METHODOLOGY/PRINCIPAL FINDINGS: DNA sequence data from five nuclear DNA loci were analyzed for population structure and haplotype distribution. Additionally, all strains were tested for survival of oxidative stress, a trait associated with microbial pathogenicity. DNA sequence analyses identified three genetic subgroups within the recombining S. cerevisiae strains that are associated with ecology, geography and virulence. Shared alleles suggest that the clinical isolates contain genetic contribution from the fruit isolates. Clinical and fruit isolates exhibit high levels of recombination, unlike the genetically homogenous soil isolates in which no recombination was detected. However, clinical and soil isolates were more resistant to oxidative stress than any other population, suggesting a correlation between survival in oxidative stress and yeast pathogenicity. CONCLUSIONS/SIGNIFICANCE: Population genetic analyses of S. cerevisiae delineated three distinct groups, comprising primarily the (i) human-associated brewery and vineyard strains, (ii) clinical and fruit isolates (iii) and wild soil isolates from eastern U.S. The interactions between S. cerevisiae and humans potentiate yeast evolution and the development of genetically, ecologically and geographically divergent groups

Application of light microscopical and ultrastructural immunohistochemistry in the study of goblet cell carcinoid in the appendix

<p>Abstract</p> <p>Background</p> <p>Goblet cell carcinoids appear less frequently in the appendix than do other carcinoids. In the presented work a case with a goblet cell carcinoid of the appendix is described.</p> <p>Methods</p> <p>Routine histological and histochemical methods were employed, with a combination of histochemistry and immunohistochemistry on one section and light and electron microscopical immunohistochemisty on paraffin-embedded material, were applied to identify the type of the carcinoid and to reveal the fine structure of cell types in the tumour nests of the appendix.</p> <p>Results</p> <p>During the biopsy of a patient who had undergone appendectomy, an infiltration with clusters of goblet cells in the submucosa of the appendix was found. After a second operation of right-sided hemicolectomy, similar clusters of goblet cells were detected in the muscle layers of the caecum. After 18 months the patient died from cirrhosis and had not developed metastases or any recurrence. Immunohistochemically the serotonin-, somatostatin-, chromogranin A- and synaptophysin-positive endocrine cells were basally attached to mucin-secreting cells. The combined staining revealed simultaneously present endocrine cells (chromogranin-A-positive) and mucin-secreting cells (PAS- or alcian blue-positive). The ultrastructural immunohistochemistry showed that chromogranin A-positive cells had discoid and pleomorphic granules and were located in tumour nests or as single cells in the appendiceal wall.</p> <p>Conclusion</p> <p>The combined histochemical and immunohistochemical procedure and the ultrastructural immunohistochemistry on archival material could contribute in clarifying the diagnosis of goblet cell carcinoid.</p

Relationship between craving and personality in treatment-seeking women with substance-related disorders

BACKGROUND: Individual differences may impact susceptibility to addiction. The impact of personality features on drug craving, however, has not been studied, particularly in women. METHODS: Ninety-five treatment-seeking women with substance dependence, abstinent for at least 5 and no more than 21 days, were investigated regarding the correlation between personality factors and craving. Personality was assessed using the Temperament and Character Inventory (TCI), the NEO Personality Inventory Revised (NEO-PI-R), and the Barratt Impulsiveness Scale version 11 (BIS-11). Cravings were assessed through the Pennsylvania Craving Scale (PCS), and the Craving Questionnaire (CQ). Anxiety and depressive symptomatology were also recorded. RESULTS: Craving scores were positively correlated with depression and negatively correlated with number of days abstinent from substance use. Also, craving scores were positively associated with the novelty-seeking factor from the TCI and the total score on the BIS-11, and negatively associated with the conscientiousness and agreeableness facets of the NEO-PI-R. CONCLUSION: Findings suggest that personality features, particularly impulsiveness, can be important predictors of craving in women, which has important implications for treatment planning

Differential lipid dependence of the function of bacterial sodium channels

The lipid bilayer is important for maintaining the integrity of cellular compartments and plays a vital role in providing the hydrophobic and charged interactions necessary for membrane protein structure, conformational flexibility and function. To directly assess the lipid dependence of activity for voltage-gated sodium channels, we compared the activity of three bacterial sodium channel homologues (NaChBac, NavMs, and NavSp) by cumulative 22Na+ uptake into proteoliposomes containing a 3:1 ratio of 1-palmitoyl 2-oleoyl phosphatidylethanolamine and different “guest” glycerophospholipids. We observed a unique lipid profile for each channel tested. NavMs and NavSp showed strong preference for different negatively-charged lipids (phosphatidylinositol and phosphatidylglycerol, respectively), whilst NaChBac exhibited a more modest variation with lipid type. To investigate the molecular bases of these differences we used synchrotron radiation circular dichroism spectroscopy to compare structures in liposomes of different composition, and molecular modeling and electrostatics calculations to rationalize the functional differences seen. We then examined pore-only constructs (with voltage sensor subdomains removed) and found that in these channels the lipid specificity was drastically reduced, suggesting that the specific lipid influences on voltage-gated sodium channels arise primarily from their abilities to interact with the voltage-sensing subdomains

Antagonistic Changes in Sensitivity to Antifungal Drugs by Mutations of an Important ABC Transporter Gene in a Fungal Pathogen

Fungal pathogens can be lethal, especially among immunocompromised populations, such as patients with AIDS and recipients of tissue transplantation or chemotherapy. Prolonged usage of antifungal reagents can lead to drug resistance and treatment failure. Understanding mechanisms that underlie drug resistance by pathogenic microorganisms is thus vital for dealing with this emerging issue. In this study, we show that dramatic sequence changes in PDR5, an ABC (ATP-binding cassette) efflux transporter protein gene in an opportunistic fungal pathogen, caused the organism to become hypersensitive to azole, a widely used antifungal drug. Surprisingly, the same mutations conferred growth advantages to the organism on polyenes, which are also commonly used antimycotics. Our results indicate that Pdr5p might be important for ergosterol homeostasis. The observed remarkable sequence divergence in the PDR5 gene in yeast strain YJM789 may represent an interesting case of adaptive loss of gene function with significant clinical implications

Genetic Architecture of Highly Complex Chemical Resistance Traits across Four Yeast Strains

Many questions about the genetic basis of complex traits remain unanswered. This is in part due to the low statistical power of traditional genetic mapping studies. We used a statistically powerful approach, extreme QTL mapping (X-QTL), to identify the genetic basis of resistance to 13 chemicals in all 6 pairwise crosses of four ecologically and genetically diverse yeast strains, and we detected a total of more than 800 loci. We found that the number of loci detected in each experiment was primarily a function of the trait (explaining 46% of the variance) rather than the cross (11%), suggesting that the level of genetic complexity is a consistent property of a trait across different genetic backgrounds. Further, we observed that most loci had trait-specific effects, although a small number of loci with effects in many conditions were identified. We used the patterns of resistance and susceptibility alleles in the four parent strains to make inferences about the allele frequency spectrum of functional variants. We also observed evidence of more complex allelic series at a number of loci, as well as strain-specific signatures of selection. These results improve our understanding of complex traits in yeast and have implications for study design in other organisms

ReCombine: A Suite of Programs for Detection and Analysis of Meiotic Recombination in Whole-Genome Datasets

In meiosis, the exchange of DNA between chromosomes by homologous recombination is a critical step that ensures proper chromosome segregation and increases genetic diversity. Products of recombination include reciprocal exchanges, known as crossovers, and non-reciprocal gene conversions or non-crossovers. The mechanisms underlying meiotic recombination remain elusive, largely because of the difficulty of analyzing large numbers of recombination events by traditional genetic methods. These traditional methods are increasingly being superseded by high-throughput techniques capable of surveying meiotic recombination on a genome-wide basis. Next-generation sequencing or microarray hybridization is used to genotype thousands of polymorphic markers in the progeny of hybrid yeast strains. New computational tools are needed to perform this genotyping and to find and analyze recombination events. We have developed a suite of programs, ReCombine, for using short sequence reads from next-generation sequencing experiments to genotype yeast meiotic progeny. Upon genotyping, the program CrossOver, a component of ReCombine, then detects recombination products and classifies them into categories based on the features found at each location and their distribution among the various chromatids. CrossOver is also capable of analyzing segregation data from microarray experiments or other sources. This package of programs is designed to allow even researchers without computational expertise to use high-throughput, whole-genome methods to study the molecular mechanisms of meiotic recombination