Correlation of frailty assessment metrics in one-year follow-up of aged care residents: a sub-study of a randomised controlled trial.

INTRODUCTION: Frailty is increasingly recognised as a dynamic syndrome, with multiple causes, dimensions and consequences. There is little understanding of how those frailty assessment metrics interact over time. The aim of this study was to describe the longitudinal correlation between five frailty metrics, namely multimorbidity, muscular strength, mood alterations, cognitive capacity, and functional capacity in a cohort study of aged care (nursing home) residents. METHODS: 248 aged care residents with Frailty Index at baseline of < 0.4 and no dementia were followed for 12 months. A multimorbidity score and an activity of daily living limitation score were created using individual items of the Frailty Index. Muscular strength was measured by grip strength. Cognitive capacity was measured using the Montreal Cognitive Assessment (MoCA) test. Mood alterations were measured using the anxiety/depression screening question from EQ-5D. We analysed the inter-individual correlation at baseline, association between baseline and future change, and within-individual correlation at baseline, 6 and 12 months. RESULTS: Population analysis shows that metrics were not associated at baseline. All of the studied metrics at baseline were associated with change in 12 months, with the exception of anxiety/depression scores. Pairwise within-individual correlation was strong between MoCA and grip strength (0.13, p = 0.02) and activity of daily living (- 0.48, p < 0.001), and between activities of daily living and multimorbidity index (0.28, p < 0.001). No within-individual correlation was found between anxiety depression score and other metrics. CONCLUSION: The results suggest an interdependence between comorbidities, physical capacity, cognition and activities of daily living in aged care residents. Comprehensive measurement of frailty-related metrics may provide improved understanding of frailty progression at later life stages.

The relationship between cleaning product exposure and respiratory and skin symptoms among healthcare workers in a hospital setting: A systematic review and meta-analysis.

Background and Aims: Several studies from multiple work settings have reported an increase in asthma and asthma-like respiratory symptoms in workers exposed to cleaning or disinfecting agents. Hospital workers perform many cleaning and disinfecting activities and may be vulnerable to respiratory and skin symptoms caused by these agents. This systematic review and meta-analysis aim to quantify the risk of asthma and asthma-like symptoms in hospital workers exposed to cleaning/disinfecting agents. A secondary aim is to assess associated risks of skin symptoms in those studies. Methods: MEDLINE, EMBASE, CDSR, CENTRAL, CINAHL databases, and references of relevant review articles were searched. NHLBI quality assessment tools were used to assess the quality of the included studies. A total of 2550 articles were retrieved and 34 studies met criteria to be included. The software R version 4.0.5 was used to perform the meta-analysis. The random-effects model was used to pool the results due to within-studies heterogeneity. Results: Meta-analysis of 10 studies evaluating the association between occupational cleaning exposures and asthma demonstrated a 35% increased risk in exposed hospital workers (meta-RR = 1.35, 95% CI: 1.09-1.68). The risk of asthma increased when workers were exposed to bleach compared with nonexposed workers (meta-RR = 1.51, 95% CI: 0.54-4.18), but was not statistically significant. Two studies investigated the relationship between respiratory and skin symptoms and produced mixed results. Conclusions: The results suggest a need for preventive practices to reduce the risk of asthma and asthma-like symptoms in hospital workers exposed to occupational cleaning/disinfecting agents. Trial registration number: CRD42020137804.

The influence of rejection episodes in recipients of bilateral corneal grafts.

We investigated whether a rejection episode in one graft was associated with rejection in the other graft, in recipients with bilateral corneal transplants. In a prospectively maintained, national register of 14,865 followed corneal grafts, 1476 patients with bilateral penetrating corneal grafts were identified. Occurrence of rejection was a risk factor for graft failure (p < 0.0001). Logistic regression was used to calculate the adjusted odds ratio for rejection in one eye following rejection in the other eye. In the subset of 1118 patients with bilateral grafts but no history of previous grafts or rejections in either eye, the adjusted odds ratio for a rejection episode in the first eye following rejection in the second was 3.27 (95% confidence interval, CI 1.85, 5.79; p < 0.001). The adjusted odds ratio was 2.04 (95% CI 1.07, 3.91; p = 0.03) for rejection in the second eye following rejection in the first. The median time between the first rejection episode in one eye and the first rejection episode in the other eye was 15 months. Patients with bilateral corneal grafts who suffer a graft rejection episode in one eye are at significantly greater odds of suffering a rejection episode in the other corneal transplant.

Radionuclide imaging correlatives of heart rate impairment during maximal exercise testing.

A lower than normal heart rate response to maximal dynamic exercise, known as chronotropic incompetence or heart rate impairment, has been demonstrated to have a poor prognosis. In order to better describe patients with this finding, 156 men with coronary heart disease were evaluated. All patients were studied with maximal exercise testing, including measurements of oxygen consumption, exercise electrocardiograms, thallium scintigraphy and radionuclide ventriculography. Chronotropic incompetence was defined as a maximal heart rate 1 standard error of the estimate below the regression line of age versus maximal heart rate on two separate exercise tests. In patients so defined, mean maximal oxygen consumption was significantly lowered and angina was the major reason for stopping exercise on the treadmill. Patients with chronotropic incompetence not limited by angina had more evidence of myocardial scar and dysfunction and had a greater prevalence of three vessel coronary disease than did patients with a normal heart rate response. Radionuclide testing results suggest that among patients with chronotropic incompetence, those with angina have a better prognosis than those who do not have angina but who may have myocardial dysfunction.

Noninvasive testing in the evaluation of myocardial ischemia: agreement among tests.

The purpose of this study was to investigate the relations among four exercise-induced phenomena--angina, ST segment depression, decrease in ejection fraction and thallium perfusion defects--and to determine their impact on aerobic capacity. One hundred fifty-six men (mean age 52 +/- 8 years) with documented coronary heart disease were studied with radionuclide ventriculography during supine bicycle exercise, thallium scintigraphy and treadmill testing with computerized electrocardiography and maximal oxygen uptake. Of 624 administered tests, 243 results (39%) were considered to indicate ischemia. The average number of abnormal tests was 1.6 per patient and, when considered as continuous variables, their results correlated poorly. Correlations did not improve when adjusting for heart rate achieved or by eliminating patients with coronary artery bypass surgery or myocardial infarction. Statistical methods of comparing degree of interest agreement yielded surprisingly weak relations among the four tests of ischemia. Treadmill performance was markedly impaired by angina, but much less impaired by other indicators of ischemia. It is concluded that the usual test responses implying ischemia have weak agreement when uniformly applied to patients with known coronary artery disease.

Use of clinical data in predicting improvement in exercise capacity after cardiac rehabilitation.

Fifty-nine men with coronary heart disease underwent 1 year of supervised aerobic exercise. They performed exercise tests for maximal oxygen uptake, ST segment analysis, thallium scintigraphy and radionuclide ventriculography before and after the year of exercise. A computerized data base that included clinical descriptors and exercise test results was retrospectively reviewed to determine whether initial features could predict the patient's response to the exercise intervention. Poor correlations were found between the initial measurements and change in maximal oxygen consumption and other indexes of training effect. Patients who initially were in the poorest state of fitness showed the most improvement with training. None of the initial features from the history and physical examination, treadmill study or radionuclide studies was a good predictor of a beneficial result from the exercise program. The usual measurements of work intensity during training were poor predictors of outcome. A significant decrease in the amount of ischemia measured by thallium perfusion scintigraphy was demonstrated after training.

Nonentrained circadian rhythms of melatonin in submariners scheduled to an 18-hour day.

The human circadian timing system has previously been shown to free run with a period slightly longer than 24 h in subjects living in the laboratory under conditions of forced desynchrony. In forced desynchrony, subjects are shielded from bright light and periodic time cues and are required to live on a day length outside the range of circadian entrainment. The work schedule used for most personnel aboard American submarines is 6 h on duty alternating with 12 h off duty. This imposed 18-h cycle is too short for human circadian synchronization, especially given that there is no bright-light exposure aboard submarines. However, crew members are exposed to 24-h stimuli that could mediate synchronization, such as clocks and social contacts with personnel who are living on a 24-h schedule. The authors investigated circadian rhythms of salivary melatonin in 20 crew members during a prolonged voyage on a Trident nuclear submarine. The authors found that in crew members living on the 18-h duty cycle, the endogenous rhythm of melatonin showed an average period of 24.35 h (n = 12, SD = 0.18 h). These data indicate that social contacts and knowledge of clock time are insufficient for entrainment to a 24-h period in personnel living by an 18-h rest-activity cycle aboard a submarine.

Calibration and standardization of bone mineral densitometers.

Measurements of bone mineral density (BMD) by four 153Gd and two x-ray bone densitometers were compared utilizing spine phantoms that simulated the human lumbar spine. The six instruments provided BMD values that differed by as much as 16%, due to differences as large as 8% in bone mineral content and as large as 7% in bone area. Instrument calibration curves, determined by measuring thin, medium, and thick hydroxyapatite blocks, were linear (r = 0.99) but had different (p less than 0.0001) slopes and intercepts. Serial measurements of spine and total body phantoms were employed to evaluate the long-term stability of 153Gd bone densitometry. These measurements of spine phantom BMD increased 1.0-2.6% (p less than 0.0001) following a software change, and measurements of total body bone density increased 4-6% after 153Gd source replacement. The changes occurred at a time when serial measurements of cylindrical calibration standards were stable, indicating that such simple standards are unable to detect and correct for changes in instrumental response. We conclude that investigators, manufacturers, and government regulatory agencies must develop and implement the following: (1) effective calibration procedures that would assure comparability among instruments, and (2) appropriate quality control phantoms that would allow the confident interpretation of serial patient measurements.

Quantitative digital radiography versus dual photon absorptiometry of the lumbar spine.

Lumbar spine bone mineral density (BMD) was measured by quantitative digital radiography, a new dual energy x-ray technique, and by 153Gd dual photon absorptiometry (DPA) in 85 patients. Each patient was measured twice by the new method and once by DPA on the same day, with repositioning between measurements. Serial measurements were made on an hydroxyapatite spine phantom embedded in tissue-equivalent plastic to evaluate the long term reproducibility of each instrument. The spinal BMD measurements with the 2 techniques were linearly related and highly correlated (r = 0.98) over a range from severely osteopenic to high normal. This correlation was not affected by the age, weight, or BMD of the patient measured. Quantitative digital radiography's long-term reproducibility using the spine phantom was stable for 180 days (coefficient of variation, 0.23%); DPA values were 3 times as variable for 170 days (coefficient of variation 0.73%) and increased 1.0% (P less than 0.0001) after a software change. The short term reproducibility of quantitative digital radiography, estimated from paired patient measurements, was 2-fold better than reported values for DPA and was independent of the patient's age, weight, or BMD. Measurement time by quantitative digital radiography was 5-8 min, with a maximum radiation exposure of 3 mrem, significantly lower than the corresponding DPA values. Quantitative digital radiography's image resolution was superior to that of DPA, enabling it to measure more bones. These advantages along with the elimination of 153Gd source changes and Nuclear Regulatory Commission licensing requirements indicate that quantitative digital radiography is the superior method for spinal BMD measurements.

Dual-conjugate wavefront generation for adaptive optics.

We present results of the isoplanatic performance of an astronomical adaptive optics system in the laboratory, by using a dual layer turbulence simulator. We describe how the performance of adaptive correction degrades with off--axis angle. These experiments demonstrate that it is now possible to produce quantifiable multi-layer turbulence in the laboratory as a precursor to constructing multi-conjugate adaptive optics.

Oxygen-induced brain vacuolation in Drosophila and a possible threshold for this response.

Wild type populations of Drosophila melanogaster were exposed to 21%, 33%, 45%, and 55% oxygen at normal atmospheric pressures. Individuals were selected randomly at 5-d intervals and inspected for vacuolation of the forebrain. Longevity of the populations was also measured. Flies in 21% and 33% oxygen had identical survivorship and even after 50 d showed little vacuolation. Flies maintained in 45% oxygen showed rapid mortality between 30-40 d and were found to have vacuolated forebrains. Populations treated in 55% oxygen declined rapidly in numbers between 20-30 d and showed severe vacuolation of the forebrain. It was considered important that normal longevity and normal aging of brain cells in 33% oxygen at standard pressure were found because similar partial pressures of pure oxygen were reported to significantly reduce longevity. It is suggested that, because insects are known to be tolerant to fairly extreme changes in total atmospheric pressure, a partial pressure of nitrogen as a diluent gas is the important factor in the toxic effects of a given pressure of oxygen. The study indicates that in a nitrogen/oxygen mix at 760 torr total pressure, the threshold to toxicity lies near, or just beyond, 300 torr oxygen. The authors indicate that preliminary findings in their current work show that if a small partial pressure of nitrogen is maintained, the total pressure can be reduced considerably without affecting this threshold level.

DXA body composition: theory and practice.

Dual energy X-ray absorptiometry (DXA) was used to measure human body composition on a high speed fan beam scanner. High and low energy attenuation pairs, produced by the various combinations of fat mass and fat-free mass in the human body, were compared to attenuation values produced by standard materials (aluminum and acrylic). These standards were measured in various combinations to construct calibration curves for fat and fat-free mass. Primary calibration of the aluminum/acrylic combinations was achieved by direct comparison to the dual energy attenuation produced by stearic acid and pure water. Whole body examinations were accomplished using three 45 s longitudinal passes of the fan beam. These passes were acquired and assembled to create a giant, isocentric fan beam with a single center of focus. In vivo precision was 0.009 g/cm2 for BMD and 425 g for fat mass and fat-free mass (s.d.).

White-light performance of a polarization-independent liquid-crystal phase modulator.

The broadband performance of a polarization-insensitive liquid-crystal phase modulator is analyzed, and its effect on an adaptive optics system is quantified.

Phase-aberration correction with dual liquid-crystal spatial light modulators.

A phase-aberration-correction system that uses high-resolution, twisted nematic liquid-crystal spatial light modulators in a Mach-Zehnder interferometer is presented. A correction algorithm is described and experimentally verified by use initially of one liquid-crystal panel. Phase aberrations are successfully removed by a single liquid-crystal panel, but unacceptably high amplitude variation is introduced into the wave front because of the phase-amplitude coupling of the spatial light modulator. A second panel is used to remove the amplitude modulation. The modified optical system with a multiplicative architecture is described, and results are presented that show the correction of phase aberrations with an amplitude variation of less than 10%.

Reproductive epigenetics.

Epigenetics refers to covalent modifications of DNA and core histones that regulate gene activity without altering DNA sequence. To date, the best-characterized DNA modification associated with the modulation of gene activity is methylation of cytosine residues within CpG dinucleotides. Human disorders associated with epigenetic abnormalities include rare imprinting diseases, molar pregnancies, and childhood cancers. Germ cell development and early embryo development are critical times when epigenetic patterns are initiated or maintained. This review focuses on the epigenetic modification DNA methylation and discusses recent progress that has been made in understanding when and how epigenetic patterns are differentially established in the male and female germlines, the mouse, and human disorders associated with abnormalities in epigenetic programming in germ cells and early embryos, as well as genetic and other modulators (e.g. nutrition and drugs) of reproductive epigenetic events.

Sleep latency measures of caffeine effects during sleep deprivation.

Studies of stimulants during sleep deprivation have used performance assessment batteries (PABs) and occasionally the multiple sleep latency test (MSLT) as measures. Another type of sleep latency test, the maintenance of wakefulness test (MWT), assesses ability to remain awake without assistance, rather than ability to go to sleep. The MWT previously has not been used in studies of stimulants during sleep deprivation. This study of caffeine during 64 h without sleep included a PAB, the MSLT, and a single MWT trial per day. The PAB and the MSLT were sensitive to caffeine effects during the first 24 h without sleep. The MWT demonstrated that caffeine improved ability to remain awake even after 2 nights of sleep deprivation. Ability to go to sleep and ability to stay awake during sleep deprivation appear to be affected differently by caffeine. PAB testing may fail to detect this stimulant effect because technicians prevent subjects from nodding off during PAB testing, an external support not available to subjects during the MWT and also not available in many real-world work environments. The MWT was more sensitive to stimulant amelioration of sleep-deprivation effects. The findings need to be validated with MWTs at other times of day and with other stimulants.

Single X-ray absorptiometry of the forearm: precision, correlation, and reference data.

The performance of a single X-ray absorptiometry (SXA) device incorporating an X-ray tube as a photon source was evaluated with respect to precision in vivo and in vitro, scan time, image quality, and correlation with an existing dual energy X-ray absorptiometry (DXA) device. SXA precision in vivo, expressed as a coefficient of variation (CV), was 0.66% for bone mineral content (BMC) and 1.05% for bone mineral density (BMD). Precision in vitro, based on 78 BMC measurements of a forearm phantom over 195 days, was 0.53%. Correlation with DXA at the 8 mm distal forearm site was high (r = 0.97 for BMC and r = 0.96 for BMD). A preliminary SXA reference database composed of 151 healthy Caucasian American women was developed to facilitate the interpretation of patient measurements. SXA scan time was 4 minutes and delivered a radiation exposure of 1.68 mrem. SXA image quality and spatial resolution were superior to SPA and comparable to DXA.

Prediction of outcome in late-stage cardiomyopathy.

One hundred thirty-three patients with dilated heart failure, 80 with coronary artery disease, and 53 with idiopathic dilated cardiomyopathy were followed for a mean of 29 months. Patients with ischemic heart disease had a worse prognosis than those classified as having idiopathic cardiomyopathy. Features from history, physical examination, and diagnostic tests done when patients were referred to our clinic were checked for univariate association with survival and were used in Cox model survival analysis to define risk groups. Neither the overall group nor either subgroup showed a relationship between ejection fraction and survival. The best variables for predicting long-term mortality included underlying coronary artery disease, basal systolic blood pressure of less than 120 mm Hg, presence of congestion on chest radiogram, and age over 64. Other variables did not improve risk prediction in the overall group. Among patients with ischemic heart disease, blood pressure, congestion, maximal heart rate on treadmill test, and the presence of left bundle branch block on the initial electrocardiogram all contributed. Only systolic blood pressure and the symptom score were related to survival in idiopathic cardiomyopathy.