EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Validation of an air-liquid interface toxicological set-up using Cu, Pd, and Ag well-characterized nanostructured aggregates and spheres.

ABSTRACT: Systems for studying the toxicity of metal aggregates on the airways are normally not suited for evaluating the effects of individual particle characteristics. This study validates a set-up for toxicological studies of metal aggregates using an air-liquid interface approach. The set-up used a spark discharge generator capable of generating aerosol metal aggregate particles and sintered near spheres. The set-up also contained an exposure chamber, The Nano Aerosol Chamber for In Vitro Toxicity (NACIVT). The system facilitates online characterization capabilities of mass mobility, mass concentration, and number size distribution to determine the exposure. By dilution, the desired exposure level was controlled. Primary and cancerous airway cells were exposed to copper (Cu), palladium (Pd), and silver (Ag) aggregates, 50-150 nm in median diameter. The aggregates were composed of primary particles <10 nm in diameter. For Cu and Pd, an exposure of sintered aerosol particles was also produced. The doses of the particles were expressed as particle numbers, masses, and surface areas. For the Cu, Pd, and Ag aerosol particles, a range of mass surface concentrations on the air-liquid interface of 0.4-10.7, 0.9-46.6, and 0.1-1.4 µg/cm2, respectively, were achieved. Viability was measured by WST-1 assay, cytokines (Il-6, Il-8, TNF-a, MCP) by Luminex technology. Statistically significant effects and dose response on cytokine expression were observed for SAEC cells after exposure to Cu, Pd, or Ag particles. Also, a positive dose response was observed for SAEC viability after Cu exposure. For A549 cells, statistically significant effects on viability were observed after exposure to Cu and Pd particles. The set-up produced a stable flow of aerosol particles with an exposure and dose expressed in terms of number, mass, and surface area. Exposure-related effects on the airway cellular models could be asserted.

Methodology for identifying particle sources in indoor environments.

Growing concern about airborne particles in indoor environments requires fast source identification in order to apply remedial actions. A methodology for identifying sources emitting particles larger than 0.5 microm was designed and applied. It includes: (1) visual inspection of interior surfaces in order to identify deposited particles and inspection of potential sources (equipment, materials, activities etc.) of airborne particles. (2) Technical measurements of airborne particles at different positions in a building with simultaneous logging of activities. (3) Isolating potential activities/particle sources in a test chamber, initially free from particles, for controlled characterizations of the particles generated. The methodology was applied in a study of three houses in southern Sweden. The results show that source identification is facilitated by knowledge of concentration variations between different rooms, real-time measurements together with activity reports and information on particle characteristics that are comparable with results from laboratory simulations. In the houses to which the methodology was applied, major particle emissions from textile handling were identified, which were likely due to detergent zeolite residues.

Management of glucocorticoid-induced osteoporosis in male veterans.

OBJECTIVE: To determine whether glucocorticoid-induced osteoporosis in male veterans was managed in accordance with American College of Rheumatology (ACR) guidelines. These guidelines recommend bone mineral density (BMD) determination at the initiation of long-term therapy with prednisone > or =7.5 mg/d, provision of hormone replacement therapy as needed, calcium and vitamin D supplementation as necessary, and antiresorptive therapy for low BMD. DESIGN: Patients receiving prednisone > or =7.5 mg/d throughout a predefined six-month period were identified through a hospital pharmacy database. Electronic and paper chart review was carried out to determine whether BMD measurement by dual-energy X-ray absorptiometry had been performed. Supplemental calcium and vitamin D intake was assessed for each patient. In addition, pharmacy records were reviewed to determine whether antiresorptive therapy was prescribed for patients with low BMD. SETTING: The Wm. S. Middleton Veterans Affairs Medical Center, Madison, WI. RESULTS: Seventy-two men met study criteria. They had been receiving oral prednisone treatment for a median of 30 months (range 6-74); mean daily dosage during the six-month study period was 12.5 mg (range 7.5-37.5). Extensive record review revealed that only six patients (8%) received recommended calcium and vitamin D, and only 43 (60%) had a BMD determination. Of those 43 men, 32 had T-scores below -1, therefore meeting ACR criteria for recommended antiresorptive therapy. However, only 12 of these 32 patients were prescribed antiresorptive therapy. Although this study was not designed to evaluate differences among clinics, there appeared to be better adherence to ACR guidelines for patients cared for in a rheumatology specialty clinic than in other clinics at the institution. CONCLUSIONS: Adherence to ACR guidelines for management of glucocorticoid-induced osteoporosis was poor. Efforts to improve the prevention and management of glucocorticoid-induced osteoporosis in male veterans are warranted.

Effects of estrogen replacement therapy on the circadian rhythms of serum cortisol and body temperature in postmenopausal women.

Estrogen replacement therapy (ERT) seems to enhance longevity in women. Both gender and aging have been shown to influence the regulation of circadian rhythms, yet little is known about the effect of ERT on circadian regulation. The aim of this study was to determine the effects of ERT (oral conjugated estrogen: Premarin, 0.625 mg) for 6-8 weeks on circadian serum cortisol by continuous blood sampling every 15 min for 24 h with simultaneous measurements of body temperature in six healthy postmenopausal women (range, 54-61 years). The results are presented as median values (range in quartiles). The circadian amplitude of cortisol increased during ERT from 20.20 (18.35, 23.61) to 25.97 (24.94, 27.74) microg/dL (p = 0.016), whereas the timing of nocturnal nadir and morning acrophase did not differ significantly. ERT lowered the 24-h body temperature from 37.03 degrees C (36.95 degrees C, 37.07 degrees C) to 36.90 degrees C (36.77 degrees C, 36.97 degrees C) (p = 0.038), but did not alter the peak and trough body temperatures significantly. These findings are noteworthy because the increased circadian amplitude of serum cortisol during ERT contrasts with the reduction in circadian amplitude seen with normal aging. The reduction in body temperature confirms the regulatory effect of ERT in thermoregulation and has implications regarding the correlation between basal metabolic rate and life span.

Pulsatile adrenocorticotropic hormone: an overview.

Adrenocorticotropic hormone (ACTH) is secreted by corticotrophic cells in pulsatile bursts. This paper reviews the extant literature on the phenomenon of pulsatile ACTH after addressing basic issues of hormone pulsatility in neuroendocrine systems. The following themes emerged from reviewing 51 studies measuring plasma ACTH at intervals of 20 min or less: marked inter-individual variability in the pattern of ACTH, the dependence of pulse identification on sampling frequency, the similarity in ACTH pulse amplitude and frequency across species, and the predominance of amplitude over frequency changes in ACTH pulses in altered physiological states. As the hypothalamic-pituitary-adrenocortical (HPA) axis plays a critical role in orchestrating adaptation and survival, the ability to modulate the shape of ACTH signals may prove to be an important means of transmitting complex information to ACTH responsive cells. The clinical and neurobiological significance of temporal alterations in ACTH secretion represents an area for future investigation.

Geriatric assessment: making it work in primary care practice.

Geriatric assessment has become an established part of medical practice, a trend driven by the growing population of older patients, positive patient outcomes, and increase interest in controlling healthcare cost. Geriatric assessment is a diagnostic process that can be performed in a variety of clinical settings, including the primary care office. The interdisciplinary assessment team usually includes at least three members: a physician, a nurse,and a social worker. Patients who appear to derive the greatest benefit are over age 75, have mild to moderate disabilities, may be at risk of nursing home placement, and may have a poor social network. For optimal effectiveness, assessment must be coupled with a comprehensive therapeutic plan and long-term follow-up.

Soccer injuries in Iceland.

We investigated the frequency, cause and location of injuries in Icelandic elite soccer in 1991. The incidence of injuries for the individual player was 34.8 +/- 5.7 per 1000 game-hours and 5.9 +/- 1.1 per 1000 practice-hours. The most common types of injuries were muscle strains (29%), ligament sprains (22%), contusions (20%), and other injuries (29%). The frequency of reinjury was markedly high, where 44% of the strains and 58% of the sprains were registered as reinjuries. Strains occurred mainly during sprinting, sprains by tackling, and contusion during other contact. Significantly more injuries occurred on artificial turf than on grass or gravel in correlation to number of hours in games and practices. Teams who had the longest pre-season preparation period obtained significantly fewer injuries during the season.

Different patterns of bacterial DNA synthesis during postantibiotic effect.

Studies on bacterial metabolism during the postantibiotic effect (PAE) period are limited but might provide insight into the nature of the PAE. We evaluated the rate of DNA synthesis in bacteria during the PAE period after a 1-h exposure of organisms in the logarithmic growth phase to various antibiotics. Staphylococcus aureus ATCC 25923 was exposed to vancomycin, dicloxacillin, rifampin, and ciprofloxacin; Escherichia coli ATCC 25922 was exposed to gentamicin, tobramycin, rifampin, imipenem, and ciprofloxacin; and Pseudomonas aeruginosa ATCC 25783 was exposed to imipenem, tobramycin, and ciprofloxacin. DNA synthesis was determined by measuring the rate of [3H]thymidine incorporation in S. aureus and E. coli and [3H]adenine incorporation in P. aeruginosa. DNA synthesis in S. aureus was suppressed during the PAE phase with vancomycin, dicloxacillin, and rifampin, it was suppressed in E. coli with rifampin, and it was suppressed in P. aeruginosa after exposure to tobramycin. Conversely, DNA synthesis was relatively enhanced in the gram-negative bacilli after exposure to imipenem and in all three species after exposure to ciprofloxacin. However, DNA synthesis in E. coli was only minimally affected after exposure to tobramycin and gentamicin. The differences in DNA synthesis observed after exposure to various antimicrobial agents suggest multiple mechanisms for the PAE.

Ultrastructural alterations of bacteria during the postantibiotic effect.

Ultrastructural alterations of Staphylococcus aureus and Pseudomonas aeruginosa were examined during the postantibiotic effect (PAE) with transmission electron microscopy. After exposure to dicloxacillin the staphylococci were characterized by an increase in the number of crosswalls, rifampin produced thickening of the cell wall, but only minimal changes were induced by gentamicin. Intracellular electrondense aggregates were observed in P. aeruginosa after exposure to imipenem, tobramycin and ciprofloxacin, and imipenem caused globoid cell formations. These alterations were not uniform in every organism, but they correlated well with the duration of the PAE determined by viable counts.

Impact of pH and cationic supplementation on in vitro postantibiotic effect.

Most studies on pharmacodynamic variables in vitro, including the postantibiotic effect (PAE), are performed at pH 7.4 in noncationic-supplemented media, a situation which may differ significantly from the true microenvironment in most infected foci. We studied the impact of five different pH levels (pH 5, 6, 7, 7.4, and 8) on the duration of the PAE, the MIC, and bactericidal activity. Acid pH was found to have in general a deleterious effect on the activity of aminoglycosides and ciprofloxacin against Escherichia coli and Pseudomonas aeruginosa, with the MIC being higher, the bactericidal rate being lower, and the PAE being shorter at pH 5 (and to a lesser extent at pH 6) than at more alkaline pH levels. Similar results were observed for imipenem against P. aeruginosa. The PAEs induced by ampicillin against E. coli and dicloxacillin against Staphylococcus aureus were not predictably dependent on the pH, whereas the PAEs induced by ciprofloxacin against S. aureus were longest at either end of the pH spectrum. The bactericidal activity of these agents was, however, pH dependent, being slower at acid pHs. The addition of 50 mg of Ca2+ and 20 mg of Mg2+ per liter of liquid medium at pH 7.4 did not affect the duration of the PAE. Since the pH in abscess cavities may be close to 5, these observations may be of importance for employment of the agents studied in closed or poorly drained infections.

The postantibiotic effect induced by antimicrobial combinations.

Antimicrobial combinations are frequently needed for the successful treatment of serious infections. Generally, the same dosing schedules are employed irrespective of whether the drugs are used singly or in combination. A postantibiotic effect (PAE) has been described for all antibiotics used singly against Gram-positive cocci, but only for non-beta-lactams against Gram-negative bacilli with the exception of carbapenems against Pseudomonas aeruginosa. The major clinical relevance of the PAE pertains to its impact on antimicrobial dosing, where agents inducing a long PAE may be administered with longer dosing intervals than currently employed, without loss of efficacy. The purpose of this study was to examine whether PAEs induced by drug combinations differed from the PAEs induced by the drugs alone, and whether a pattern of synergism, addition or antagonism could be defined in this regard. The study organisms, 7 strains of Staphylococcus aureus, 4 strains of Escherichia coli, 4 strains of Klebsiella pneumoniae and 6 strains of Ps. aeruginosa, were exposed to several beta-lactams, aminoglycosides, rifampin and ciprofloxacin singly and in combination. The antimicrobial combinations used against S. aureus affected the PAE in either an additive or an indifferent manner when compared to the PAEs induced by the drugs as single agents. Enhancement of PAEs against Gram-negative bacilli was primarily dependent on the ability of each individual drug to induce a PAE. Thus, for a combination of drugs where both agents induced a PAE individually, the final PAE was a rough mathematical sum of the individual PAEs (addition). When only one of the agents induced a PAE, the final result was similar to the PAE of that particular drug (indifference). Ciprofloxacin seemed to be an exception to this rule, since it did not increase the PAE of a PAE producing drug, despite exhibiting a PAE itself. Rifampin was unique in that it prolonged the PAE in a marked synergistic fashion, when employed with one or more other PAE-producing agents. Further studies in vivo are clearly needed to confirm these observations, but they could have significant impact on the design of dosing regimens for antimicrobial combinations.