Increased multi-drug resistance among the elderly on admission to the hospital--a 12-year surveillance study.

Resistance to antimicrobials continues to increase worldwide. Data suggest that older patients are among the main reservoirs of multidrug-resistant organisms (MDROs) in the hospital. We hypothesized that older patients (≥ 65 years of age) are more likely to harbor MDRO at hospital admission. We compared rates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and multidrug-resistant gram-negative bacteria (MDRGN) recovered from clinical cultures within the first 48 h of admission to an adult acute care hospital between the elderly (≥ 65 years old) and young per 1000 age-stratified admissions over a 12-year study period. Trends in antimicrobial resistance, sites of recovery and species for MDRGN were also characterized. An average of 7534 positive bacterial cultures were collected per year. The admission prevalence per 1000 age-stratified admissions was consistently higher among the elderly for all three MDRO under investigation. Among the elderly, the admission prevalence increased significantly for VRE (0.89 in 1998 to 3.62 in 2009 per 1000 admissions; p < 0.001) and MDRGN (1.41 in 1998 to 11.33 in 2009 per 1000 admissions; p < 0.001). Percentage resistant for all three MDRO increased as well. These data suggest that elderly patients are contributing substantially to the influx of MDRO into the hospital setting

Humpback whale song revolutions continue to spread from the central into the eastern South Pacific

Funding: COCIBA grants of USFQ National Geographic Society - W396-15; NERC Sea Mammal Research Unit - NE/R015007/1; Project CETACEA Ecuador Royal Society - NF140667, UF160081; Rufford Foundation.Cultural transmission of behaviour is an important aspect of many animal communities ranging from humans to birds. Male humpback whales (Megaptera novaeangliae) sing a repetitive, stereotyped, socially learnt and culturally transmitted song display that slowly evolves each year. Most males within a population sing the same, slow-evolving song type; but in the South Pacific, song ‘revolutions’ have led to rapid and complete replacement of one song type by another introduced from a neighbouring population. Songs spread eastwards, from eastern Australia to French Polynesia, but the easterly extent of this transmission was unknown. Here, we investigated whether song revolutions continue to spread from the central (French Polynesia) into the eastern (Ecuador) South Pacific region. Similarity analyses using three consecutive years of song data (2016–2018) revealed that song themes recorded in 2016–2018 French Polynesian song matched song themes sung in 2018 Ecuadorian song, suggesting continued easterly transmission of song to Ecuador, and vocal connectivity across the entire South Pacific Ocean basin. This study demonstrates songs first identified in western populations can be transmitted across the entire South Pacific, supporting the potential for a circumpolar Southern Hemisphere cultural transmission of song and a vocal culture rivalled in its extent only by our own.Publisher PDFPeer reviewe

Sensitive electrochemiluminescence (ECL) immunoassays for detecting lipoarabinomannan (LAM) and ESAT-6 in urine and serum from tuberculosis patients.

BackgroundTuberculosis (TB) infection was responsible for an estimated 1.3 million deaths in 2017. Better diagnostic tools are urgently needed. We sought to determine whether accurate TB antigen detection in blood or urine has the potential to meet the WHO target product profiles for detection of active TB.Materials and methodsWe developed Electrochemiluminescence (ECL) immunoassays for Lipoarabinomannan (LAM) and ESAT-6 detection with detection limits in the pg/ml range and used them to compare the concentrations of the two antigens in the urine and serum of 81 HIV-negative and -positive individuals with presumptive TB enrolled across diverse geographic sites.ResultsLAM and ESAT-6 overall sensitivities in urine were 93% and 65% respectively. LAM and ESAT-6 overall sensitivities in serum were 55% and 46% respectively. Overall specificity was ≥97% in all assays. Sensitivities were higher in HIV-positive compared to HIV-negative patients for both antigens and both sample types, with signals roughly 10-fold higher on average in urine than in serum. The two antigens showed similar concentration ranges within the same sample type and correlated.ConclusionsLAM and ESAT-6 can be detected in the urine and serum of TB patients, regardless of the HIV status and further gains in clinical sensitivity may be achievable through assay and reagent optimization. Accuracy in urine was higher with current methods and has the potential to meet the WHO accuracy target if the findings can be transferred to a point-of-care TB test

Aged Murine Hematopoietic Stem Cells Drive Aging-Associate Immune Remodeling

Aging-associated remodeling of the immune system impairs its functional integrity and contributes to increased morbidity and mortality in the elderly. Aging of hematopoietic stem cells (HSCs), from which all cells of the adaptive immune system ultimately originate, might play a crucial role in the remodeling of the aged immune system. We recently reported that aging of HSCs is, in part, driven by elevated activity of the small RhoGTPase Cdc42 and that aged HSCs can be rejuvenated in vitro by inhibition of the elevated Cdc42 activity in aged HSCs with the pharmacological compound CASIN. To study the quality of immune systems stemming selectively from young or aged HSCs, we established a HSC transplantation model in T- and B-cell-deficient young RAG1−/− hosts. We report that both phenotypic and functional changes in the immune system on aging are primarily a consequence of changes in the function of HSCs on aging and, to a large extent, independent of the thymus, as young and aged HSCs reconstituted distinct T- and B-cell subsets in RAG1−/− hosts that mirrored young and aged immune systems. Importantly, aged HSCs treated with CASIN reestablished an immune system similar to that of young animals, and thus capable of mounting a strong immune response to vaccination. Our studies further imply that epigenetic signatures already imprinted in aged HSCs determine the transcriptional profile and function of HSC-derived T and B cells

A Novel Sensitive Immunoassay Targeting the 5-Methylthio-d-Xylofuranose-Lipoarabinomannan Epitope Meets the WHO's Performance Target for Tuberculosis Diagnosis.

The only currently commercialized point-of-care assay for tuberculosis (TB) that measures lipoarabinomannan (LAM) in urine (Alere LF-LAM) has insufficient sensitivity. We evaluated the potential of 100 novel monoclonal antibody pairs targeting a variety of LAM epitopes on a sensitive electrochemiluminescence platform to improve the diagnostic accuracy. In the screening, many antibody pairs showed high reactivity to purified LAM but performed poorly at detecting urinary LAM in clinical samples, suggesting differences in antigen structure and immunoreactivity of the different LAM sources. The 12 best antibody pairs from the screening were tested in a retrospective case-control study with urine samples from 75 adults with presumptive TB. The best antibody pair reached femtomolar analytical sensitivity for LAM detection and an overall clinical sensitivity of 93% (confidence interval [CI], 80% to 97%) and specificity of 97% (CI, 85% to 100%). Importantly, in HIV-negative subjects positive for TB by sputum smear microscopy, the test achieved a sensitivity of 80% (CI, 55% to 93%). This compares to an overall sensitivity of 33% (CI, 20% to 48%) of the Alere LF-LAM and a sensitivity of 13% (CI, 4% to 38%) in HIV-negative subjects in the same sample set. The capture antibody targets a unique 5-methylthio-d-xylofuranose (MTX)-dependent epitope in LAM that is specific to the Mycobacterium tuberculosis complex and shows no cross-reactivity with fast-growing mycobacteria or other bacteria. The present study provides evidence that improved assay methods and reagents lead to increased diagnostic accuracy. The results of this work have informed the development of a sensitive and specific novel LAM point-of-care assay with the aim to meet the WHO's performance target for TB diagnosis

A proposal for the retrospective identification and categorization of older people with functional impairments in scientific studies : recommendations of the Medication and Quality of Life in Frail Older Persons (MedQoL) research group

When treating older adults, a main factor to consider is physical frailty. Because specific assessments in clinical trials are frequently lacking, critical appraisal of treatment evidence with respect to functional status is challenging. Our aim was to identify and categorize assessments for functional status given in clinical trials in older adults to allow for a retrospective characterization and indirect comparison of treatment evidence from these cohorts. We conducted 4 separate systematic reviews of randomized and nonrandomized controlled clinical trials in older people with hypertension, diabetes, depression, and dementia. All assessments identified that reflected functional status were analyzed. Assessments were categorized across 4 different functional status levels. These levels span from functionally not impaired, slightly impaired, significantly impaired, to severely impaired/disabled. If available from the literature, cut-offs for these 4 functioning levels were extracted. If not, or if the existing cut-offs did not match the predefined functional levels, cut-off points were defined by an expert group composed of geriatricians, pharmacists, pharmacologists, neurologists, psychiatrists, and epidemiologists using a patient-centered approach. We identified 51 instruments that included measures of functional status. Although some of the assessments had clearly defined cut-offs across our predefined categories, many others did not. In most cases, no cut-offs existed for slightly impaired or severely impaired older adults. Missing cut-offs or values to adjust were determined by the expert group and are presented as described. The functional status assessments that were identified and operationalized across 4 functional levels could now be used for a retrospective characterization of functional status in randomized controlled trials and observational studies. Allocated categories only serve as approximations and should be validated head-to-head in future studies. Moreover, as general standard, upcoming studies involving older adults should include and explicitly report functional impairment as a baseline characteristic of all participants enrolled

Psychological distress, fear and coping strategies during the second and third waves of the COVID-19 pandemic in Southern Germany

Background: The COVID-19 pandemic has imposed enormous psychological discomfort and fear across the globe, including Germany. Objectives: To assess the levels of COVID-19 associated psychological distress and fear amongst Southern German population, and to identify their coping strategies. Methods: A cross-sectional survey using an online questionnaire was conducted in healthcare and community settings in the region of Ulm, Southern Germany. Assessment inventories were the Kessler Psychological Distress Scale (K-10), the Brief Resilient Coping Scale (BRCS), and the Fear of COVID-19 Scale (FCV-19S), which were valid and reliable tools. Results: A total of 474 Individuals participated in the study. The mean age was 33.6 years, and 327 (69%) were females. Most participants (n = 381, 80.4%) had high levels of psychological distress, whereas only 5.1% had high levels of fear, and two-thirds of participants showed higher levels of coping. Moderate to very high levels of psychological distress were associated with being female, living alone, distress due to employment changes, experiencing financial impact, having multiple co-morbidities, being a smoker, increased alcohol use over the previous 6 months, contact with COVID-19 cases and healthcare providers for COVID-19-related stress. Individuals who wer

What works to prevent falls in older adults dwelling in long term care facilities and hospitals? An umbrella review of meta-analyses of randomised controlled trials

Preventing falls in long term care facilities (LTCF) and hospitals is an international priority. Many interventions have been investigated and summarised in meta-analyses (MA) and there is a need to synthesise the top of the hierarchy of evidence in one place. Therefore we conducted an umbrella review of MA of randomised controlled trials (RCTs) of falls prevention interventions LTCF and hospitals. Two independent reviewers searched major electronic databases from inception till October 2014 for MA containing ≥3 RCTs investigating any intervention to prevent falls in LTCF or hospitals in older adults aged ≥60 years. Methodological quality was assessed by the AMSTAR tool and data were narratively synthesised. The methodological quality of the MA was moderate to high across the 10 included MA. Nine MA provided data for LTCF and only two considered hospital settings. Only one MA defined a fall and two reported adverse events (although minor). Consistent evidence suggests that multifactorial interventions reduce falls (including the rate, risk and odds of falling) in LTCF and hospitals. Inconsistent evidence exists for exercise and vitamin D as single interventions in LTCF, whilst no MA has investigated this in hospitals. No evidence exists for hip protectors and medication review on falls in LTCF. In conclusion, multifactorial interventions appear to be the most effective interventions to prevent falls in LTCF and hospital settings. This is not without limitations and more high quality RCTs are needed in hospital settings in particular. Future RCTs and MA should clearly report adverse events

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: Results from the European Project on OSteoArthritis (EPOSA)

People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Methods Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. Results The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Conclusions Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA.The Indicators for Monitoring COPD and Asthma - Activity and Function in the Elderly in Ulm study (IMCA - ActiFE) is supported by the European Union (No.: 2005121) and the Ministry of Science, Baden-Württemberg. The Italian cohort study is part of the National Research Council Project on Aging (PNR). The Longitudinal Aging Study Amsterdam (LASA) is financially supported by the Dutch Ministry of Health, Welfare and Sports. The Peñagrande study was partially supported by the National Fund for Health Research (Fondo de Investigaciones en Salud) of Spain (project numbers FIS PI 05/1898; FIS RETICEF RD06/0013/1013 and FIS PS09/02143). The Swedish Twin Registry is supported in part by the Swedish Ministry of Higher Education. The Hertfordshire Cohort Study was supported by the Medical Research Council, UK