Evaluation of a novel immunoassay to detect p-Tau Thr127 in the CSF to distinguish Alzheimer disease from other dementias

OBJECTIVE: To investigate whether p-tau T217 assay in cerebrospinal fluid (CSF) can distinguish Alzheimer's disease from other dementias and healthy controls. METHODS: We developed and validated a novel Simoa immunoassay to detect p-tau T217 in CSF. There was a total of 190 participants from three cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy subjects (n = 44). RESULTS: The p-tau T217 assay (cut-off 242 pg/ml) identified AD subjects with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, 88% specificity compared favorably with p-tau T181 ELISA (52 pg/ml) showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity, 97% sensitivity. The assay distinguished AD patients from age-matched healthy subjects (cut-off 163 pg/ml, sensitivity 98%, specificity 93%) similarly to p-tau T181 ELISA (cut-off 60 pg/ml, 96% sensitivity and 86% specificity). In AD patients, we found a strong correlation between p-tau T217-tau and p-tau T181, t-tau and Aβ40 but not with Aβ42. CONCLUSIONS: This study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggests that the new p-tau T217 assay has a potential as an AD diagnostic test in the clinical evaluation. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes AD from other dementias and healthy controls

Magnitude of potentially inappropriate prescribing in Germany among older patients with generalized anxiety disorder

<p>Abstract</p> <p>Background</p> <p>Several medications commonly used to treat generalized anxiety disorder (GAD) have been designated "potentially inappropriate" for use in patients aged ≥65 years because their risks may outweigh their potential benefits. The actual extent of use of these agents in clinical practice is unknown, however.</p> <p>Methods</p> <p>Using a database with information from encounters with general practitioners (GP) in Germany, we identified all patients, aged ≥65 years, with any GP office visits or dispensed prescriptions with a diagnosis of GAD (ICD-10 diagnosis code F41.1) between 10/1/2003 and 9/30/2004 ("GAD patients"). Among GAD-related medications (including benzodiazepines, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors, venlafaxine, hydroxyzine, buspirone, pregabalin, and trifluoperazine), long-acting benzodiazepines, selected short-acting benzodiazepines at relatively high dosages, selected TCAs, and hydroxyzine were designated "potentially inappropriate" for use in patients aged ≥ 65 years, based on published criteria.</p> <p>Results</p> <p>A total of 975 elderly patients with GAD were identified. Mean age was 75 years, and 72% were women; 29% had diagnoses of comorbid depression. Forty percent of study subjects received potentially inappropriate agents – most commonly, bromazepam (10% of all subjects), diazepam (9%), doxepin (7%), amitriptyline (5%), and lorazepam (5%). Twenty-three percent of study subjects received long-acting benzodiazepines, 10% received short-acting benzodiazepines at relatively high doses, and 12% received TCAs designated as potentially inappropriate.</p> <p>Conclusion</p> <p>GPs in Germany often prescribe medications that have been designated as potentially inappropriate to their elderly patients with GAD – especially those with comorbid depressive disorders. Further research is needed to ascertain whether there are specific subgoups of elderly patients with GAD for whom the benefits of these medications outweigh their risks.</p

Structure and evolution of the mouse pregnancy-specific glycoprotein (Psg) gene locus

BACKGROUND: The pregnancy-specific glycoprotein (Psg) genes encode proteins of unknown function, and are members of the carcinoembryonic antigen (Cea) gene family, which is a member of the immunoglobulin gene (Ig) superfamily. In rodents and primates, but not in artiodactyls (even-toed ungulates / hoofed mammals), there have been independent expansions of the Psg gene family, with all members expressed exclusively in placental trophoblast cells. For the mouse Psg genes, we sought to determine the genomic organisation of the locus, the expression profiles of the various family members, and the evolution of exon structure, to attempt to reconstruct the evolutionary history of this locus, and to determine whether expansion of the gene family has been driven by selection for increased gene dosage, or diversification of function. RESULTS: We collated the mouse Psg gene sequences currently in the public genome and expressed-sequence tag (EST) databases and used systematic BLAST searches to generate complete sequences for all known mouse Psg genes. We identified a novel family member, Psg31, which is similar to Psg30 but, uniquely amongst mouse Psg genes, has a duplicated N1 domain. We also identified a novel splice variant of Psg16 (bCEA). We show that Psg24 and Psg30 / Psg31 have independently undergone expansion of N-domain number. By mapping BAC, YAC and cosmid clones we described two clusters of Psg genes, which we linked and oriented using fluorescent in situ hybridisation (FISH). Comparison of our Psg locus map with the public mouse genome database indicates good agreement in overall structure and further elucidates gene order. Expression levels of Psg genes in placentas of different developmental stages revealed dramatic differences in the developmental expression profile of individual family members. CONCLUSION: We have combined existing information, and provide new information concerning the evolution of mouse Psg exon organization, the mouse Psg genomic locus structure, and the expression patterns of individual Psg genes. This information will facilitate functional studies of this complex gene family

Adverse Drug Reactions Related Hospital Admissions in Persons Aged 60 Years and over, The Netherlands, 1981–2007: Less Rapid Increase, Different Drugs

Background: Epidemiologic information on time trends of Adverse Drug Reactions (ADR) and ADR-related hospitalizations is scarce. Over time, pharmacotherapy has become increasingly complex. Because of raised awareness of ADR, a decrease in ADR might be expected. The aim of this study was to determine trends in ADR-related hospitalizations in the older Dutch population. Methodology and Principal Findings: Secular trend analysis of ADR-related hospital admissions in patients ≥60 years between 1981 and 2007, using the National Hospital Discharge Registry of the Netherlands. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of ADR-related hospital admissions were used as outcome measures in each year of the study. Between 1981 and 2007, ADR-related hospital admissions in persons ≥60 years increased by 143%. The overall standardized incidence rate increased from 23.3 to 38.3 per 10,000 older persons. The increase was larger in males than in females. Since 1997, the increase in incidence rates of ADR-related hospitalizations flattened (percentage annual change 0.65%), compared to the period 1981-1996 (percentage annual change 2.56%). Conclusion/Significance: ADR-related hospital admissions in older persons have shown a rapidly increasing trend in the Netherlands over the last three decades with a temporization since 1997. Although an encouraging flattening in the increasing trend of ADR-related admissions was found around 1997, the incidence is still rising, which warrants sustained attention to this problem

Socioeconomic determinants of psychotropic drug utilisation among elderly: a national population-based cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Psychotropic drugs are commonly utilised among the elderly. This study aimed to analyse whether two socioeconomic determinants - income and marital status - are associated with differences in utilisation of psychotropic drugs and potentially inappropriate psychotropic drugs among elderly in Sweden.</p> <p>Methods</p> <p>All individuals aged 75 years and older who had purchased a psychotropic drug in Sweden during 2006 were included (68.7% women, n = 384712). Data was collected from national individual-based registers. Outcome measures were utilisation of three or more psychotropic drugs and utilisation of potentially inappropriate psychotropic drugs, as classified by the Swedish National Board of Health and Welfare.</p> <p>Results</p> <p>Individuals with low income were more likely to utilise three or more psychotropic drugs compared to those with high income; adjusted odds ratio (aOR) 1.12 (95% confidence interval [CI] 1.10-1.14). The non-married had a higher probability for utilising three or more psychotropic drugs compared to the married (aOR 1.22; CI 1.20-1.25). The highest probability was observed among the divorced and the never married. Potentially inappropriate psychotropic drugs were more common among individuals with low compared to high income (aOR 1.14; CI 1.13-1.16). Compared to the married, potentially inappropriate psychotropic drug utilisation occurred more commonly among the non-married (aOR 1.08; CI 1.06-1.10). The never married and the divorced had the highest probability.</p> <p>Conclusions</p> <p>There was an association between socioeconomic determinants and psychotropic drug utilisation. The probability for utilising potentially inappropriate psychotropics was higher among individuals with low income and among the non-married.</p

Gonadal suppression alters axillary steroid secretions in men, but does that affect olfactory social signaling?

Background and objective: Luteinizing hormone-releasing hormone agonists (LHRHa) suppress gonadal hormone production and are commonly used to treat prostate cancer (PC) in men and conditions ranging from uterine fibroids to estrogen-sensitive cancers in women. They are also used to delay sexual development in children considering gender reassignment or experiencing premature puberty. As chemically castrating agents, LHRHa may affect cutaneous steroid secretions, which, in turn, could alter body odor and influence the psycho-sexual dynamics between individuals. The objectives of the present study were to determine (1) if LHRHa indeed alter cutaneous skin secretions, and (2) whether this leads to perceivable changes in body odor. Material and methods: Axillary skin secretions were collected on new cotton T-shirts worn by men undergoing androgen deprivation therapy with an LHRHa to treat PC (n = 10), both before starting the LHRHa and 3 months later. Healthy heterosexual university students (50 males, 50 females) were recruited to smell and rate the shirts for their masculinity, attractiveness, and intensity of odor. Liquid chromatography-mass spectrometry (LC-MS) was also used to analyze steroids extracted from the shirt samples. Results: LC-MS showed a statistically significant decline in the concentration of the androgenic metabolites, androsterone and 5α-androstane-3,17-dione. This confirms that LHRHa drugs that suppress gonadal hormone production markedly reduce cutaneous secretion of androgenic metabolic intermediates in adult males. However, no differences in odor were detected in the ratings of the shirts by male, female, nor male and female raters combined for any of the three variables assessed. Possible reasons why the human sniffers failed to perceive a change in odor are explored. Conclusion: Our data document that LHRHa alter steroid skin secretions in older men, but whether such changes alter the olfactory signals that might influence psychosocial interactions remains unresolved

Health status and quality of life among older adults in rural Tanzania

BACKGROUND\ud \ud Increasingly, human populations throughout the world are living longer and this trend is developing in sub-Saharan Africa. In developing African countries such as Tanzania, this demographic phenomenon is taking place against a background of poverty and poor health conditions. There has been limited research on how this process of ageing impacts upon the health of older people within such low-income settings.\ud \ud OBJECTIVE\ud \ud The objective of this study is to describe the impacts of ageing on the health status, quality of life and well-being of older people in a rural population of Tanzania.\ud \ud DESIGN\ud \ud A short version of the WHO Survey on Adult Health and Global Ageing questionnaire was used to collect information on the health status, quality of life and well-being of older adults living in Ifakara Health and Demographic Surveillance System, Tanzania, during early 2007. Questionnaires were administered through this framework to 8,206 people aged 50 and over.\ud \ud RESULTS\ud \ud Among people aged 50 and over, having good quality of life and health status was significantly associated with being male, married and not being among the oldest old. Functional ability assessment was associated with age, with people reporting more difficulty in performing routine activities as age increased, particularly among women. Reports of good quality of life and well-being decreased with increasing age. Women were significantly more likely to report poor quality of life (odds ratio 1.31; p<0.001, 95% CI 1.15-1.50).\ud \ud CONCLUSIONS\ud \ud Older people within this rural Tanzanian setting reported that the ageing process had significant impacts on their health status, quality of life and physical ability. Poor quality of life and well-being, and poor health status in older people were significantly associated with marital status, sex, age and level of education. The process of ageing in this setting is challenging and raises public health concerns

Prevalence of inappropriate medication using Beers criteria in Japanese long-term care facilities

BACKGROUND: The prevalence and risk factors of potentially inappropriate medication use among the elderly patients have been studied in various countries, but because of the difficulty of obtaining data on patient characteristics and medications they have not been studied in Japan. METHODS: We conducted a retrospective cross-sectional study in 17 Japanese long-term care (LTC) facilities by collecting data from the comprehensive MDS assessment forms for 1669 patients aged 65 years and over who were assessed between January and July of 2002. Potentially inappropriate medications were identified on the basis of the 2003 Beers criteria. RESULTS: The patients in the sample were similar in terms of demographic characteristics to those in the national survey. Our study revealed that 356 (21.1%) of the patients were treated with potentially inappropriate medication independent of disease or condition. The most commonly inappropriately prescribed medication was ticlopidine, which had been prescribed for 107 patients (6.3%). There were 300 (18.0%) patients treated with at least 1 inappropriate medication dependent on the disease or condition. The highest prevalence of inappropriate medication use dependent on the disease or condition was found in patients with chronic constipation. Multiple logistic regression analysis revealed psychotropic drug use (OR = 1.511), medication cost of per day (OR = 1.173), number of medications (OR = 1.140), and age (OR = 0.981) as factors related to inappropriate medication use independent of disease or condition. Neither patient characteristics nor facility characteristics emerged as predictors of inappropriate prescription. CONCLUSION: The prevalence and predictors of inappropriate medication use in Japanese LTC facilities were similar to those in other countries