Reference values and clinical predictors of bone strength for HR-pQCT-based distal radius and tibia strength assessments in women and men.

Reference values for radius and tibia strength using multiple-stack high-resolution peripheral quantitative computed tomography (HR-pQCT) with homogenized finite element analysis are presented in order to derive critical values improving risk prediction models of osteoporosis. Gender and femoral neck areal bone mineral density (aBMD) were independent predictors of bone strength. INTRODUCTION: The purpose was to obtain reference values for radius and tibia bone strength computed by using the homogenized finite element analysis (hFE) using multiple stacks with a HR-pQCT. METHODS: Male and female healthy participants aged 20-39 years were recruited at the University Hospital of Bern. They underwent interview and clinical examination including hand grip, gait speed and DXA of the hip. The nondominant forearm and tibia were scanned with a double and a triple-stack protocol, respectively, using HR-pQCT (XCT II, SCANCO Medical AG). Bone strength was estimated by using the hFE analysis, and reference values were calculated using quantile regression. Multivariable analyses were performed to identify clinical predictors of bone strength. RESULTS: Overall, 46 women and 41 men were recruited with mean ages of 25.1 (sd 5.0) and 26.2 (sd 5.2) years. Sex-specific reference values for bone strength were established. Men had significantly higher strength for radius (mean (sd) 6640 (1800) N vs. 4110 (1200) N; p < 0.001) and tibia (18,200 (4220) N vs. 11,970 (3150) N; p < 0.001) than women. In the two multivariable regression models with and without total hip aBMD, the addition of neck hip aBMD significantly improved the model (p < 0.001). No clinical predictors of bone strength other than gender and aBMD were identified. CONCLUSION: Reference values for radius and tibia strength using multiple HR-pQCT stacks with hFE analysis are presented and provide the basis to help refining accurate risk prediction models. Femoral neck aBMD and gender were significant predictors of bone strength.

[Catalogue of learning goals for pregraduate education in geriatric medicine. A recommendation of the German Geriatric Society (DGG), the German Society of Gerontology and Geriatrics (DGGG), the Austrian Society of Geriatrics and Gerontology (ÖGGG) and the Swiss Society of Geriatric Medicine (SFGG) on the basis of recommendations of the European Union of Medical Specialists Geriatric Medicine Section (UEMS-GMS) 2013]. / Lernzielkatalog für die studentische Lehre im Fachbereich "Geriatrie" an Fakultäten für Humanmedizin. Eine Empfehlung der Deutschen Gesellschaft für Geriatrie (DGG), der deutschen Gesellschaft für Gerontologie und Geriatrie (DGGG), der Österreichischen Gesellschaft für Geriatrie und Gerontologie (ÖGGG) und der Schweizerischen Fachgesellschaft für Geriatrie (SFGG) auf Basis der Empfehlungen der Europäischen Facharztvereinigung-Sektion Geriatrie (UEMS-GMS) 2013.

Sound knowledge in the care and management of geriatric patients is essential for doctors in almost all medical subspecialties. Therefore, it is important that pregraduate medical education adequately covers the field of geriatric medicine. However, in most medical faculties in Europe today, learning objectives in geriatric medicine are often substandard or not even explicitly addressed. As a first step to encourage undergraduate teaching in geriatric medicine, the European Union of Medical Specialists -Geriatric Medicine Section (UEMS-GMS) recently developed a catalogue of learning goals using a modified Delphi technique in order to encourage education in this field. This catalogue of learning objectives for geriatric medicine focuses on the minimum requirements with specific learning goals in knowledge, skills and attitudes that medical students should have acquired by the end of their studies.In order to ease the implementation of this new, competence-based curriculum among the medical faculties in universities teaching in the German language, the authors translated the published English language curriculum into German and adapted it according to medical language and terms used at German-speaking medical faculties and universities of Austria, Germany and Switzerland. This article contains the final German translation of the curriculum. The Geriatric Medicine Societies of Germany, Austria, and Switzerland formally endorse the present curriculum and recommend that medical faculties adapt their curricula for undergraduate teaching based on this catalogue.

Comparing Prevalence of Sarcopenia Using Twelve Sarcopenia Definitions in a Large Multinational European Population of Community-Dwelling Older Adults.

OBJECTIVES: Multinational prevalence data on sarcopenia among generally healthy older adults is limited. The aim of the study was to assess prevalence of sarcopenia in the DO-HEALTH European trial based on twelve current sarcopenia definitions. SETTING AND PARTICIPANTS: This is an analysis of the DO-HEALTH study including 1495 of 2157 community-dwelling participants age 70+ years from Germany, France, Portugal, and Switzerland with complete measurements of the sarcopenia toolbox including muscle mass by DXA, grip strength, and gait speed. MEASUREMENTS: The twelve sarcopenia definitions applied were Asian Working Group on Sarcopenia (AWGS1), AWGS2, Baumgartner, Delmonico, European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, EWGSOP2-lower extremities, Foundation for the National Institutes of Health (FNIH1), FNIH2, International Working Group on Sarcopenia in Older People (IWGS), Morley, and Sarcopenia Definitions and Outcomes Consortium (SDOC). RESULTS: Mean age was 74.9 years (SD 4.4); 63.3% were women. Sarcopenia prevalence ranged between 0.7% using the EWGSOP2 or AWGS2 definition, up to 16.8% using the Delmonico definition. Overall, most sarcopenia definitions, including Delmonico (16.8%), Baumgartner (12.8%), FNIH1(10.5%), IWGS (3.6%), EWGSOP1 (3.4%), SDOC (2.0%), Morley (1.3%), and AWGS1 (1.1%) tended to be higher than the prevalence based on EWGSOP2 (0.7%). In contrast, the definitions AWGS2 (0.7%), EWGSOP2-LE (1.1%), FNIH2 (1.0%) - all based on muscle mass and muscle strength - showed similar lower prevalence as EWGSOP2 (0.7%). Moreover, most sarcopenia definitions did not overlap on identifying sarcopenia on an individual participant-level. CONCLUSION: In this multinational European trial of community-dwelling older adults we found major discordances of sarcopenia prevalence both on a population- and on a participant- level between various sarcopenia definitions. Our findings suggest that the concept of sarcopenia may need to be rethought to reliably and validly identify people with impaired muscle health.

Performance of a Novel Handheld Bioelectrical Impedance Device for Assessing Muscle Mass in Older Inpatients.

OBJECTIVES: To investigate practicality and repeatability of a handheld compared to a state-of-the-art multisegmental bioelectrical impedance analysis (BIA) device to facilitate screening of sarcopenia in older inpatients. DESIGN AND SETTING: Cross-sectional study in a geriatric rehabilitation hospital. PARTICIPANTS: 207 inpatients aged 70+. MEASUREMENTS: In a first phase, appendicular skeletal muscle mass index (ASMI) was measured using the handheld Biody xpertZm II BIA device (n=100). In a second phase, ASMI was obtained using the multisegmental Biacorpus RX 4004M device (n=107). Repeatability of BIA devices was compared in subgroups of patients (handheld BIA device: n=36, multisegmental BIA device: n=46) by intra-class correlation (ICC) and Bland-Altman plots. RESULTS: Overall, measurement failure was seen in 31 patients (31%) tested with the handheld BIA device compared to one patient (0.9%) using the multisegmental BIA device (p<0.001). Main reasons for measurement failure were inability of patients to adopt the position necessary to use the handheld BIA device and device failure. The mean difference of two ASMI measurements in the same patient was 0.32 (sd 0.85) using the handheld BIA device compared to 0.02 kg/m2 (sd 0.07) using the multisegmental device (adjusted mean difference between both groups -0.35, 95% confidence interval (CI) -0.61 to -0.09 kg/m2). Congruently, Bland-Altman plots showed poor agreement with the handheld compared to the multisegmental BIA device. CONCLUSION: The handheld BIA device is neither a practical nor reliable device for assessing muscle mass in older rehabilitation inpatients.

Predictive Abilities of the Frailty Phenotype and the Swiss Frailty Network and Repository Frailty Index for Non-Home Discharge and Functional Decline in Hospitalized Geriatric Patients.

BACKGROUND: Frailty is increasingly applied as a measure to predict clinical outcomes, but data on the predictive abilities of frailty measures for non-home discharge and functional decline in acutely hospitalized geriatric patients are scarce. OBJECTIVES: The aim of this study was to investigate the predictive ability of the frailty phenotype and a frailty index currently validated as part of the ongoing Swiss Frailty Network and Repository Study based on clinical admission data for non-home discharge and functional decline in acutely hospitalized older patients. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Data were analyzed from 334 consecutive hospitalized patients of a tertiary acute care geriatric inpatient clinic admitted between August 2020 and March 2021. MEASUREMENTS: We assessed frailty using 1) the frailty phenotype and 2) the Swiss Frailty Network and Repository Study (SFNR) frailty index based on routinely available clinical admission data. Predictive abilities of both frailty measures were analyzed for the clinical outcomes of non-home discharge and functional decline using multivariate logistic regression models and receiver operating characteristic curves (ROC). RESULTS: Mean age was 82.8 (SD 7.2) years and 55.4% were women. Overall, 170 (53.1%) were frail based on the frailty phenotype and 220 (65.9%) based on the frailty index. Frail patients based on the frailty phenotype were more likely to be discharged non-home (55 (32.4%) vs. 26 (17.3%); adjusted OR 2.4 (95% CI, 1.4, 5.1)). Similarly, frail patients based on the frailty index were more likely to be discharged non-home compared to non-frail patients (76 (34.6%) vs. 9 (7.9%); adjusted OR, 5.5 (95% CI, 2.6, 11.5)). Both, the frailty phenotype and the frailty index were similarly associated with functional decline (adjusted OR 2.7 (95% CI, 1.5, 4.9); adjusted OR 2.8 (95% CI 1.4, 5.5)). ROC analyses showed best discriminatory accuracy for the frailty index for non-home discharge (area under the curve 0.76). CONCLUSIONS: Frailty using the SFNR-frailty index and the frailty phenotype is a promising measure for prediction of non-home discharge and functional decline in acutely hospitalized geriatric patients. Further study is needed to define the most valid frailty measure.

Sarcopenia in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI): A Systematic Review of the Literature.

BACKGROUND: In older patients, sarcopenia is a prevalent disease associated with negative outcomes. Sarcopenia has been investigated in patients undergoing transcatheter aortic valve implantation (TAVI), but the criteria for diagnosis of the disease are heterogeneous. This systematic review of the current literature aims to evaluate the prevalence of sarcopenia in patients undergoing TAVI and to analyse the impact of sarcopenia on clinical outcomes. METHODS: A comprehensive search of the literature has been performed in electronic databases from the date of initiation until March 2020. Using a pre-defined search strategy, we identified studies assessing skeletal muscle mass, muscle quality and muscle function as measures for sarcopenia in patients undergoing TAVI. We evaluated how sarcopenia affects the outcomes mortality at ≥1 year, prolonged length of hospital stay, and functional decline. RESULTS: We identified 18 observational studies, enrolling a total number of 9'513 patients. For assessment of skeletal muscle mass, all included studies used data from computed tomography. Cut-off points for definition of low muscle mass were heterogeneous, and prevalence of sarcopenia varied between 21.0% and 70.2%. In uni- or multivariate regression analysis of different studies, low muscle mass was found to be a significant predictor of mortality, prolonged length of hospital stay, and functional decline. No interventional study was identified measuring the effect of nutritional or physiotherapy interventions on sarcopenia in TAVI patients. CONCLUSIONS: Sarcopenia is highly prevalent among patients undergoing TAVI, and negatively affects important outcomes. Early diagnosis of this condition might allow a timely start of nutritional and physiotherapy interventions to prevent negative outcomes in TAVI patients.

Effects of Health Risk Assessment and Counselling on Fruit and Vegetable Intake in Older People: A Pragmatic Randomised Controlled Trial.

OBJECTIVES: Interventions to increase fruit and vegetable intake among community-dwelling older people have shown mixed effects. We investigated whether an intervention based on an initial multidimensional health risk assessment and subsequent physician-lead nutrition counselling has favourable effects on dietary intake among community-dwelling older people. DESIGN: Randomised controlled trial comparing the intervention versus usual care. SETTING AND PARTICIPANTS: Non-disabled persons aged 65 years or older at an ambulatory geriatric clinic in Bucharest, Romania, allocated to intervention (n=100) and control (n=100) groups. INTERVENTION: Participants received a computer-generated health profile report based on answers to a health risk assessment questionnaire, followed by monthly individual counselling sessions with a geriatrician on topics related to health promotion and disease prevention, with a special focus on adequate fruit and vegetable consumption. MEASUREMENTS: Fruit and vegetable intake at baseline and at 6-month follow-up. RESULTS: At baseline, fruit and vegetable intake was below the recommended five portions per day in most study participants (85% in the intervention group, and 86% among controls, respectively). At six months, intake increased in the intervention group from a median of 3.8 to 4.6 portions per day, and decreased in the control group due to a seasonal effect from a median of 3.8 to 3.1 portions per day. At six months, fruit and vegetable consumption was significantly higher among persons in the intervention group as compared to controls (median difference 1.4 portions per day, 95% confidence interval 1.1-1.7, p<0.001). CONCLUSION: Personalised food-based dietary guidance, delivered as part of multidimensional preventive health counselling during geriatric clinic visits, results in relevant improvement of fruit and vegetable intake in community-dwelling older adults.

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring.

Approximate entropy (ApEn) of blood pressure (BP) can be easily measured based on software analysing 24-h ambulatory BP monitoring (ABPM), but the clinical value of this measure is unknown. In a prospective study we investigated whether ApEn of BP predicts, in addition to average and variability of BP, the risk of hypertensive crisis. In 57 patients with known hypertension we measured ApEn, average and variability of systolic and diastolic BP based on 24-h ABPM. Eight of these fifty-seven patients developed hypertensive crisis during follow-up (mean follow-up duration 726 days). In bivariate regression analysis, ApEn of systolic BP (P<0.01), average of systolic BP (P=0.02) and average of diastolic BP (P=0.03) were significant predictors of hypertensive crisis. The incidence rate ratio of hypertensive crisis was 14.0 (95% confidence interval (CI) 1.8, 631.5; P<0.01) for high ApEn of systolic BP as compared to low values. In multivariable regression analysis, ApEn of systolic (P=0.01) and average of diastolic BP (P<0.01) were independent predictors of hypertensive crisis. A combination of these two measures had a positive predictive value of 75%, and a negative predictive value of 91%, respectively. ApEn, combined with other measures of 24-h ABPM, is a potentially powerful predictor of hypertensive crisis. If confirmed in independent samples, these findings have major clinical implications since measures predicting the risk of hypertensive crisis define patients requiring intensive follow-up and intensified therapy.

Electronic alert system for improving appropriate thromboprophylaxis in hospitalized medical patients: a randomized controlled trial.

Essentials Venous thromboembolism (VTE) prophylaxis in hospitalized medical patients remains inconsistent. We implemented an electronic alert system featuring a validated risk assessment model for VTE. In this randomized controlled study, the e-alert system did not improve VTE prophylaxis. Many electronic alerts were ignored by ordering physicians. SUMMARY: Background The use of thromboprophylaxis among acutely ill hospitalized medical patients remains inconsistent. Objective To improve thromboprophylaxis use by implementing a computer-based alert system combined with a Geneva Risk Score calculation tool in the electronic patient chart and order entry system. Patients/Methods Consecutive patients admitted to the general internal medicine wards of the University Hospital Bern, Switzerland were randomized to the alert group, in which an alert and the Geneva Risk Score calculation tool was issued in the electronic patient chart, or to the control group, in which no alert was issued. The primary endpoint was the rate of appropriate thromboprophylaxis during hospital stay. Results Overall, 1593 patients (alert group, 804; control group, 789) were eligible for analysis. The median age was 67 years (interquartile range, 53-79 years) and 47% were female. Appropriate thromboprophylaxis was administered to 536 (66.7%) patients from the alert group and to 526 (66.7%) patients from the control group. Among the 804 patients from the alert group, a total of 446 (55.5%) either had no score calculation by the physician in charge (n = 348) or had a calculated score result that was inconsistent with information from the patient chart (n = 98). Appropriate thromboprophylaxis was less often administered to patients with no score or an inconsistent score result than to 358 patients with a consistent score result (62.6% versus 71.8%). Conclusions The electronic alert (e-alert) system did not improve appropriate thromboprophylaxis, most likely because many e-alerts were ignored by ordering physicians. The use of appropriate thromboprophylaxis in the control group was higher than expected.

Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis: 1-year follow-up data of a randomized-controlled trial.

Essentials Acute iliofemoral deep vein thrombosis can be treated with catheter-directed thrombolysis (CDT). We performed a randomized trial comparing conventional CDT versus ultrasound-assisted CDT (USAT). Clinical and duplex sonographic outcomes at 12 months were similar in the CDT and USAT groups. In both groups, incidence of postthrombotic syndrome was very low with good quality of life. SUMMARY: Background In patients with acute iliofemoral deep vein thrombosis (IFDVT), catheter-directed thrombolysis (CDT) aims to prevent the postthrombotic syndrome (PTS). Adding intravascular high-frequency, low-power ultrasound energy to CDT does not seem to improve the immediate thrombolysis results but its impact on clinical outcomes at 12 months is not known. Patients/Methods In this randomized-controlled trial, 48 patients (mean age 50 ± 21 years; 52% women) with acute IFDVT were randomized to conventional CDT (n = 24) or ultrasound-assisted CDT (USAT; n = 24). In both groups, a fixed-dose thrombolysis regimen (20 mg r-tPA over 15 h) was used, followed by routine stenting of residual venous obstruction. At 12 months, PTS and venous disease severity (Villalta score and revised Venous Clinical Severity Score [rVCSS]), disease-specific quality of live (QOL; CIVIQ-20) and duplex-sonographic outcomes were assessed. Results Among the 45 surviving patients, 40 (89%; 95% confidence interval [CI] 76-96%) patients were free from PTS (defined as Villalta score < 5 points; 83%, 95% CI 61-95% in the USAT and 96%, 95% CI 77-100% in the CDT group), with a similar mean total Villalta score of 2.3 ± 2.9 vs. 1.7 ± 1.6, and a mean total rVCSS of 3.0 ± 3.5 vs. 2.7 ± 2.9 in the USAT and the CDT groups, respectively. Both groups had good disease-specific QOL with a CIVIQ-20 score of 29.4 ± 11.8 vs. 26.1 ± 7.8, respectively. Primary (100% vs. 92%) and secondary (100% vs. 96%) iliofemoral patency rates and presence of femoro-popliteal venous reflux (39% vs. 33%) were similar in both groups. Conclusion The addition of intravascular ultrasound energy to conventional CDT for the treatment of acute IFDVT did not have any impact on relevant clinical or duplex sonographic outcomes, which were favorable in both study groups. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier:NCT01482273.

Inappropriate medication use in community-residing older persons.

BACKGROUND: Elderly patients taking inappropriate drugs are at increased risk for adverse outcomes. We investigated the prevalence of inappropriate drug use and its predisposing factors in community-residing older persons. METHODS: We conducted in-home interviews with 414 subjects aged 75 years and older living in the community of Santa Monica, Calif. Inappropriate medication use was evaluated using explicit criteria developed through a modified Delphi consensus process. These criteria identified drugs that should generally be avoided in elderly community-residing subjects regardless of dosage, duration of therapy, or clinical circumstances. RESULTS: Based on these conservative criteria, 14.0% of the subjects were using at least one inappropriate drug. The most common examples were long-acting benzodiazepines, persantine, amitriptyline, and chlorpropamide. Subjects using three or more prescription drugs, compared with one or two, were more likely to be taking an inappropriate medication (odds ratio, 3.9; 95% confidence interval, 1.9 to 7.9). Furthermore, subjects with depressive symptoms had a higher risk of receiving inappropriate medications than nondepressive subjects (odds ratio, 2.2; 95% confidence interval, 1.1 to 4.1). CONCLUSIONS: Inappropriate drug use is a common problem in community-residing older persons. The risk of inappropriate drug use is increased in patients taking multiple medications and in patients with depressive symptoms.

A randomized trial of in-home visits for disability prevention in community-dwelling older people at low and high risk for nursing home admission.

BACKGROUND: In-home preventive visits with multidimensional geriatric assessments can delay the onset of disabilities in older people. METHODS: This was a stratified randomized trial. There were 791 participants, community-dwelling people in Bern, Switzerland, older than 75 years. The participants' risk status was based on 6 baseline predictors of functional deterioration. The intervention consisted of annual multidimensional assessments and quarterly follow-up in-home visits by 3 public health nurses (nurses A, B, and C), who, in collaboration with geriatricians, evaluated problems, gave recommendations, facilitated adherence with recommendations, and provided health education. Each nurse was responsible for conducting the home visits in 1 ZIP code area. RESULTS: After 3 years, surviving participants at low baseline risk in the intervention group were less dependent in instrumental activities of daily living (ADL) compared with controls (odds ratio, 0.6; 95% confidence interval, 0.3-1.0; P = .04). Among subjects at high baseline risk, there were no favorable intervention effects on ADL and an unfavorable increase in nursing home admissions (P= .02). Despite the similar health status of subjects, nurse C identified fewer problems in the subjects who were visited compared with those assessed by nurses A and B. Subgroup analysis revealed that among low-risk subjects visited by nurses A and B, the intervention had favorable effects on instrumental ADL (P = .005) and basic ADL (P = .009), reduced nursing home admissions (P = .004), and resulted in net cost savings in the third year (US $1403 per person per year). Among low-risk subjects visited by nurse C, the intervention had no favorable effects. CONCLUSIONS: These data suggest that this intervention can reduce disabilities among elderly people at low risk but not among those at high risk for functional impairment, and that these effects are likely related to the home visitor's performance in conducting the visits.

Health risk appraisal for older people in general practice using an expert system: a pilot study.

The prevention of disability in later life is a major challenge facing industrialised societies. Primary care practitioners are well positioned to maintain and promote health in older people, but the British experience of population-wide preventive interventions has been disappointing. Health risk appraisal (HRA), an emergent information-technology-based approach from the USA, has the potential for fulfilling some of the objectives of the National Service Framework for Older People. Information technology and expert systems allow the perspectives of older people on their health and health risk behaviours to be collated, analysed and converted into tailored health promotion advice without adding to the workload of primary care practitioners. The present paper describes a preliminary study of the portability of HRA to British settings. Cultural adaptation and feasibility testing of a comprehensive health risk assessment questionnaire was carried out in a single group practice with 12,500 patients, in which 58% of the registered population aged 65 years and over participated in the study. Eight out of 10 respondents at all ages found the questionnaire easy or very easy to understand and complete, although more than one-third had or would have liked assistance. More than half felt that the length of the questionnaire was about right, and one respondent in 10 disliked some questions. Of those who completed the questionnaire and received tailored, written health promotion advice, 39% provided feedback on this with comments that can be used for increasing the acceptability of tailored advice. These findings have informed a wider exploratory study in general practice.

Kinetics of prednisolone and endogenous cortisol suppression in the elderly.

The kinetics of prednisolone after intravenous prednisolone and oral prednisone were investigated in 19 young (23 to 34 years) and 12 elderly (65 to 89 years) subjects. The systemic availability of unbound prednisolone after oral prednisone and the apparent interconversion of prednisolone into prednisone and vice versa (reflecting the activity of the 11 beta-hydroxydehydrogenase) were independent of age. The total exposure of the elderly subjects to prednisolone was increased because the nonrenal (5.7 +/- 1.0 vs. 7.7 +/- 1.6 ml/min/kg, mean +/- SD; P less than 0.001) and renal (0.9 +/- 0.3 vs. 2.9 +/- 0.7 ml/min/kg; P less than 0.001) clearances of unbound prednisolone were lower in the elderly. The fractional clearance of 6 beta-hydroxyprednisolone (reflecting the activity of the 6 beta-hydroxylase) decreased linearly with the metabolic clearance of prednisolone. Despite increased prednisolone exposure, elderly subjects had higher endogenous cortisol concentrations. It was concluded that elderly subjects exhibit higher concentrations of both total and unbound prednisolone. Despite this greater exposure of target tissues, there appears to be less suppression of endogenous cortisol concentrations in plasma compared with younger subjects.

Fleroxacin clinical pharmacokinetics.

Fleroxacin is a new member of the class of fluoroquinolones. The drug has good activity (i.e. minimum inhibitory concentrations at less than 2 mg/L against 90% of strains) against a wide range of Gram-positive and Gram-negative bacteria. High performance liquid chromatography is used to determine concentrations of fleroxacin and its metabolites in biological fluids. Absorption of orally ingested drug is rapid as the peak plasma concentration of approximately 5 mg/L is reached in 1 to 2h after a single dose of 400mg. The systemic availability is close to 100%. Fleroxacin is poorly bound to plasma proteins (23%) and exhibits excellent tissue distribution. Renal clearance accounts for 60 to 70% of elimination. The drug is metabolised to form antimicrobially active N-demethyl-fleroxacin and inactive N-oxide-fleroxacin. In multiple dose studies the accumulation ratio of a once-daily dosage regimen is about 1.3, as predicted from the elimination half-life of 10 to 12h. Compared with ciprofloxacin, fleroxacin has a greater systemic availability and a longer half-life. Fleroxacin concentrations are higher in elderly patients, but further studies are needed to establish whether a dosage reduction should be recommended for this age group. In patients with renal disease dosage adjustment is recommended since a decreased renal clearance of fleroxacin leads to a significant prolongation of the elimination half-life. Fleroxacin is only poorly eliminated by peritoneal dialysis or haemodialysis. The most important drug-drug interaction is a decrease in systemic availability of fleroxacin after ingestion of aluminium- or magnesium-containing antacids. There is no evidence of a significant interaction between fleroxacin and theophylline. Only limited data are available on adverse reactions of fleroxacin. The most important adverse effects appear to be photosensitivity and a dose-dependent incidence of central nervous system reactions including sleep disorders.

Impacts of geriatric evaluation and management programs on defined outcomes: overview of the evidence.

Comprehensive geriatric assessment is a technique for multidimensional diagnosis of frail elderly people with the purpose of planning and/or delivering medical, psychosocial, and rehabilitative care. When comprehensive geriatric assessment is coupled with some therapy, then the term geriatric evaluation and management (GEM) will be used. Following a brief history of comprehensive geriatric assessment, we describe the varied patterns of GEM program organization and review the literature of studies examining GEM effectiveness. Program diversity complicates drawing firm conclusions about GEM effects; however, the vast majority of studies report positive, if not uniformly significant, results. Our analysis suggests that much of the variability in findings is due to sample size limitations. In order to reach conclusions of program effects across studies and to avoid problems of small sample sizes, we undertook a formal meta-analysis. In this initial meta-analysis, we sought to evaluate the effect of GEM programs on a single outcome: mortality. We pooled all published GEM controlled trials into four major groups: inpatient consultation services, inpatient GEM units, home assessment services, and outpatient GEM programs. Meta-analysis of 6-month mortality demonstrates a 39% reduction of mortality for inpatient consultation services (odds ratio 0.61, 95% confidence interval 0.46-0.81, P = 0.0008) and a 37% reduction of mortality for inpatient GEM units (odds ratio 0.63, 95% CI 0.42-0.93, P = 0.02). Home assessment services reduced mortality by 29% (odds ratio 0.71, 95% CI 0.55-0.90, P = 0.005). On the other hand, no significant survival effect was found for outpatient GEM programs (odds ratio 0.96, 95% confidence interval 0.61-1.49).(ABSTRACT TRUNCATED AT 250 WORDS)

Multidimensional risk assessment versus age as criterion for retirement of airline pilots.

OBJECTIVE: To determine whether airline pilots over the age of 60 pose a hazard to aviation safety and whether risk assessment could replace age-based retirement. DATA SOURCES: A computer-assisted literature search (MEDLINE), expert consultation, and government reports. STUDY SELECTION: Original studies on flight performance and pilot age; sudden incapacitation, neuropsychological testing, and/or medication use in pilots; and/or non-invasive testing for predicting sudden death or stroke in asymptomatic subjects. DATA EXTRACTION: Pertinent results and methods data were abstracted from the 49 included studies. DATA SYNTHESIS: No study on aircraft accidents or pilot performance has shown an increased accident risk for over-60-year-old pilots. Normal age-related cognitive changes probably have minimal impact on aviation safety up to age 70, given above average health, education, and experience in airline pilots. Cognitive tests have not been validated for predicting flight performance safety, but they can detect early stages of cognitive disease. Cardiovascular incapacitation risk increases with age, but risk factor profiles and non-invasive tests could identify pilots with non-acceptable risk. CONCLUSIONS: An improved medical certification test could identify those pathologic conditions that might occur more frequently in older subjects. If pilots also underwent adequate performance testing, a gradual increase of the retirement age to approximately age 70 would seem justified. In the future, a longitudinal database should be established to validate medical tests for their ability to predict a pilot's accident risk. Using individual pilots as their own controls might be more sensitive than using population-based norm values. Progress in this field would advance medical assessment for other groups such as air traffic controllers or automobile drivers.

Effectiveness of preventive in-home geriatric assessment in well functioning, community-dwelling older people: secondary analysis of a randomized trial.

OBJECTIVES: To determine whether preventive in-home comprehensive geriatric assessment (CGA) prevents functional decline in community-dwelling older persons with different baseline functional status: (1) without any basic activities of daily living (BADL) dependency at baseline; and (2) without any instrumental ADL (IADL) and basic ADL dependency at baseline. DESIGN: Subgroup analyses of a 3-year randomized controlled trial. SETTING: The city of Santa Monica, California. PARTICIPANTS: Participants came from the original population (n = 414) of community-living older persons aged 75 years and older who participated in a trial testing the effectiveness of annual preventive in-home CGA. For the first subgroup analysis, we excluded subjects (n = 27) who were dependent in one or more BADL before randomization (final sample size, n = 387); for the second subgroup analysis, we excluded 93 additional subjects who were dependent in one or more IADL before randomization (final sample size, n = 294). INTERVENTION: Annual preventive in-home CGA, with quarterly home visits by gerontologic nurse practitioners, for 3 years. MEASUREMENTS: Functional status data were collected through yearly in-home interviews by independent observers. Subjects were classified as (1) independent in both BADL and IADL, (2) dependent in IADL but independent in BADL, or (3) dependent in both IADL and BADL. RESULTS: In both subgroup analyses, there was no difference in survival between intervention and control subjects. In the subgroup with no BADL impairment at baseline, intervention subjects spent significantly fewer days dependent in both BADL and IADL during each year of the study (5 days vs 14 days, P = .022; 13 vs 33, P = .016; and 19 vs 44, P = .014 for years 1, 2, and 3, respectively) and over all 3 years combined (36 days vs 92 days, P = .016) in bivariate analyses. In multivariate analyses, the intervention reduced time spent in complete (BADL and IADL) dependency (P = .028). In the subgroup of subjects without any IADL or BADL impairment at baseline, no significant differences were apparent in the number of days spent in complete independence and days spent in complete dependency. Intervention group subjects spent more days in partial dependency during Year 1 (24 days vs 9 days, P = .021), but the difference was not significant during Year 2 (47 vs 29, P = .088), Year 3 (49 vs 41, P = .370), and over all 3 years combined (120 vs 79, P = .123) as well as in multivariate analysis (P = .062). CONCLUSION: These findings support the hypothesis that in-home preventive visits delay the onset of disability in people without initial BADL impairment. Further studies in larger samples are needed to determine optimal intervention strategies and effectiveness among well functioning older people.

The association between chronic illness and functional change among participants in a comprehensive geriatric assessment program.

OBJECTIVE: To examine the association between chronic illness and functional status change during a 3-year period in older people enrolled in an in-home comprehensive geriatric assessment (CGA) and preventive care program. DESIGN: Secondary analysis of data from a longitudinal cohort study. SETTING: Santa Monica, California. PARTICIPANTS: Two hundred two community-dwelling older persons (mean age at baseline was 81 years, 70% were women, and 72% reported good health) randomized to the intervention group in a trial of in-home comprehensive geriatric assessment and preventive care. MEASUREMENTS: We studied 13 common chronic illnesses/conditions determined clinically from an annual comprehensive evaluation by gerontologic nurse practitioners (GNPs) in consultation with study geriatricians. These target conditions included hypertension, osteoarthritis, coronary artery disease, obesity, undernutrition, urinary incontinence, sleep disorders, falls, gait/balance disorders, hearing and vision deficits, depression, and unsafe home environment. The dependent variable was functional change as measured by instrumental activities of daily living (IADL) and basic activities of daily living (BADL) assessed at baseline and annually for 3 years by independent research personnel. Potential confounding variables, including comorbid conditions and other subject characteristics, were controlled for in the analyses. RESULTS: Although functional status was similar at baseline, the presence of certain target conditions in this sample was associated significantly with functional decline in IADL and BADL during the 3-year period. Four conditions (gait/balance disorders, depression, unsafe home environment, and coronary artery disease) were associated with significant declines in IADL, and four conditions (gait/balance disorders, depression, hypertension, and urinary incontinence) were associated with significant declines in BADL. Conversely, subjects with obesity had no significant change in IADL or BADL throughout the study period and had less decline in IADL compared with nonobese subjects. CONCLUSIONS: Certain chronic conditions, particularly gait/balance disorders and depression, are associated with significant decline in functional status in older persons who receive CGA. These findings may help identify older persons at risk for greatest functional decline despite participation in CGA and may also suggest the need for more effective intervention strategies in these individuals.