Predicting falls in older adults: an umbrella review of instruments assessing gait, balance, and functional mobility.

BACKGROUND: To review the validated instruments that assess gait, balance, and functional mobility to predict falls in older adults across different settings. METHODS: Umbrella review of narrative- and systematic reviews with or without meta-analyses of all study types. Reviews that focused on older adults in any settings and included validated instruments assessing gait, balance, and functional mobility were included. Medical and allied health professional databases (MEDLINE, PsychINFO, Embase, and Cochrane) were searched from inception to April 2022. Two reviewers undertook title, abstract, and full text screening independently. Review quality was assessed through the Risk of Bias Assessment Tool for Systematic Reviews (ROBIS). Data extraction was completed in duplicate using a standardised spreadsheet and a narrative synthesis presented for each assessment tool. RESULTS: Among 2736 articles initially identified, 31 reviews were included; 11 were meta-analyses. Reviews were primarily of low quality, thus at high risk of potential bias. The most frequently reported assessments were: Timed Up and Go, Berg Balance Scale, gait speed, dual task assessments, single leg stance, functional Reach Test, tandem gait and stance and the chair stand test. Findings on the predictive ability of these tests were inconsistent across the reviews. CONCLUSIONS: In conclusion, we found that no single gait, balance or functional mobility assessment in isolation can be used to predict fall risk in older adults with high certainty. Moderate evidence suggests gait speed can be useful in predicting falls and might be included as part of a comprehensive evaluation for older adults.

Implementation fidelity of the Falls Management Exercise Programme: a mixed methods analysis using a conceptual framework for implementation fidelity.

OBJECTIVES: Falls in older adults cause significant morbidity and mortality and incur cost to health and care services. The Falls Management Exercise (FaME) programme is a 24-week intervention for older adults that, in clinical trials, improves balance and functional strength and leads to fewer falls. Similar but more modest outcomes have been found when FaME is delivered in routine practice. Understanding the degree to which the programme is delivered with fidelity is important if 'real-world' delivery of FaME is to achieve the same magnitude of outcome as in clinical trials. The objective of this study was to examine the implementation fidelity of FaME when delivered in the community to inform quality improvement strategies that maximise programme effectiveness. STUDY DESIGN: A mixed methods implementation study of FaME programme delivery. METHODS: Data from programme registers, expert observations of FaME classes, and semistructured interviews with FaME instructors were triangulated using a conceptual framework for implementation fidelity. Quantitative data were analysed using descriptive statistics. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: In total, 356 participants enrolled on 29 FaME programmes, and 143 (40%) participants completed at least 75% of the classes within a programme. Observations showed that 72%-78% of programme content was delivered, and 80%-84% quality criteria were met. Important content that was most often left out included home exercises, Tai Chi moves, and floor work, whereas quality items most frequently missed out included asking about falls in the previous week, following up attendance absence and explaining the purpose of exercises. Only 24% of class participants made the expected strength training progression. Interviews with FaME instructors helped explain why elements of programme content and quality were not delivered. Strategies for improving FaME delivery were established and helped to maintain quality and fidelity. CONCLUSIONS: FaME programmes delivered in the 'real world' can be implemented with a high degree of fidelity, although important deviations were found. Facilitation strategies could be used to further improve programme fidelity and maximise participant outcomes.

The combined effect of Parathyroid hormone (1-34) and whole-body Vibration exercise in the treatment of postmenopausal OSteoporosis (PaVOS study): a randomized controlled trial.

Treatment effects of combining teriparatide and whole-body vibration exercise (WBV) vs teriparatide alone in twelve months were compared using bone mineral density (BMD), bone microarchitecture, and bone turnover markers. We found an increased effect in lumbar spine BMD by adding WBV to teriparatide in postmenopausal osteoporotic women. INTRODUCTION: The parathyroid hormone (PTH) analogue teriparatide is an effective but expensive anabolic treatment for osteoporosis. Whole-body vibration exercise (WBV) has been found to stimulate muscle and bone strength in some studies. Animal data demonstrate a beneficial effect on bone when combining PTH with mechanical loading. The aim of this study was to investigate if combining WBV exercise and teriparatide treatment gives additional beneficial effects on bone compared to teriparatide alone in postmenopausal women with osteoporosis. METHODS: The PaVOS study is a randomized controlled trial where postmenopausal osteoporotic women starting teriparatide 20 µg/day were randomized to WBV + teriparatide or teriparatide alone. WBV consisted of three sessions a week (12 min, including 1:1 ratio of exercise:rest). Bone mineral density (BMD) and bone microarchitecture, bone turnover markers, and sclerostin measurements were obtained. Data were analyzed using a linear mixed regression model with adjustment for baseline values or robust cluster regression in an intention-to-treat (ITT) analysis. RESULTS: Thirty-five women were randomized (17 in teriparatide + WBV group and 18 in teriparatide group). At 12 months, both groups increased significantly in BMD at the lumbar spine. The teriparatide + WBV group increased by (mean ± SD) 8.90% ± 5.47 and the teriparatide group by 6.65% ± 5.51. The adjusted treatment effect of adding WBV to teriparatide was statistically significant at 2.95% [95% CI = 0.14-5.77; P = 0.040]. Markers of bone turnover increased significantly in both groups at three and six months with no significant difference between groups. No other treatment effects were observed in hip BMD, bone microarchitecture parameters, or sclerostin levels in either group. CONCLUSION: Twelve months of WBV and teriparatide had a significant clinically relevant treatment effect in lumbar spine BMD compared to teriparatide alone in postmenopausal osteoporotic women. ClinicalTrials.gov :(NCT02563353).

Chair based exercise in community settings: a cluster randomised feasibility study.

BACKGROUND: Some older people who find standard exercise programmes too strenuous may be encouraged to exercise while remaining seated - chair based exercises (CBE). We previously developed a consensus CBE programme (CCBE) following a modified Delphi process. We firstly needed to test the feasibility and acceptability of this treatment approach and explore how best to evaluate it before undertaking a definitive trial. METHODS: A feasibility study with a cluster randomised controlled trial component was undertaken to 1. Examine the acceptability, feasibility and tolerability of the intervention and 2. Assess the feasibility of running a trial across 12 community settings (4 day centres, 4 care homes, 4 community groups). Centres were randomised to either CCBE, group reminiscence or usual care. Outcomes were collected to assess the feasibility of the trial parameters: level of recruitment interest and eligibility, randomisation, adverse events, retention, completion of health outcomes, missing data and delivery of the CCBE. Semi- structured interviews were conducted with participants and care staff following the intervention to explore acceptability. RESULTS: 48% (89 out of 184 contacted) of eligible centres were interested in participating with 12 recruited purposively. 73% (94) of the 128 older people screened consented to take part with 83 older people then randomised following mobility testing. Recruitment required greater staffing levels and resources due to 49% of participants requiring a consultee declaration. There was a high dropout rate (40%) primarily due to participants no longer attending the centres. The CCBE intervention was delivered once a week in day centres and community groups and twice a week in care homes. Older people and care staff found the CCBE intervention largely acceptable. CONCLUSION: There was a good level of interest from centres and older people and the CCBE intervention was largely welcomed. The trial design and governance procedures would need to be revised to maximise recruitment and retention. If the motivation for a future trial is physical health then this study has identified that further work to develop the CCBE delivery model is warranted to ensure it can be delivered at a frequency to elicit physiological change. If the motivation for a future trial is psychological outcomes then this study has identified that the current delivery model is feasible. TRIAL REGISTRATION: ISRCTN27271501 . Date registered: 30/01/2018.

A comprehensive fracture prevention strategy in older adults: the European Union Geriatric Medicine Society (EUGMS) statement.

Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society, in collaboration with the International Association of Gerontology and Geriatrics for the European Region, the European Union of Medical Specialists, and the International Osteoporosis Foundation-European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.

Is calcaneal quantitative ultrasound useful as a prescreen stratification tool for osteoporosis?

Calcaneal quantitative ultrasound (QUS) is attractive as a prescreening tool for osteoporosis, alternative to dual-energy X-ray absorptiometry. We investigated the literature of the usability of calcaneal QUS. We found large heterogeneity between studies and uncertainty about cutoff, device, and measured variable. Despite osteoporosis-related fractures being a major health issue, osteoporosis remains underdiagnosed. Dual-energy X-ray absorptiometry (DXA) of the hip or spine is currently the preferred method for diagnosis of osteoporosis, but the method is limited by low accessibility. QUS is a method for assessing bone alternative to DXA. The aim of this systematic review was to explore the usability of QUS as a prescreen stratification tool for assessment of osteoporosis. Studies that evaluated calcaneal QUS with DXA of the hip or spine as the gold standard was included. We extracted data from included studies to calculate number of DXAs saved and misclassification rates at cutoffs equal to high sensitivity and/or specificity. The number of DXAs saved and percentage of persons misclassified were measures of usability. We included 31 studies. Studies were heterogeneous regarding study characteristics. Analyses showed a wide spectrum of percentage of DXAs saved (2.7-68.8%) and misclassification rates (0-12.4%) depending on prescreen strategy and study characteristics, device, measured variable, and cutoff. Calcaneal QUS is potentially useful as a prescreen tool for assessment of osteoporosis. However, there is no consensus of device, variable, and cutoff. Overall, there is no sufficient evidence to recommend a specific cutoff for calcaneal QUS that provides a certainty level high enough to rule in or out osteoporosis. Calcaneal QUS in a prescreen or stratification algorithm must be based on device-specific cutoffs that are validated in the populations for which they are intended to be used.

[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.

A European survey of older peoples' preferences, and perceived barriers and facilitators to inform development of a medication-related fall-prevention patient portal.

PURPOSE: Falls are a major and growing health care problem in older adults. A patient portal has the potential to provide older adults with fall-prevention advice to reduce fall-risk. However, to date, the needs and preferences regarding a patient portal in older people who have experienced falls have not been explored. This study assesses content preferences, potential barriers and facilitators with regard to using a patient portal, as perceived by older people who have experienced falls, and explores regional differences between European participants. METHODS: We conducted a survey of older adults attending an outpatient clinic due to a fall or fall-related injury, to explore their content preferences, perceived barriers, and facilitators with respect to a fall-prevention patient portal. Older adults (N = 121, 69.4% female, mean age: 77.9) were recruited from seven European countries. RESULTS: Almost two-thirds of respondents indicated they would use a fall-prevention patient portal. The portal would preferably include information on Fall-Risk-Increasing Drugs (FRIDs), and ways to manage other related/relevant medical conditions. Facilitators included a user-friendly portal, with easily accessible information and physician recommendations to use the portal. The most-commonly-selected barriers were privacy issues and usage fees. A family member's recommendation to use the portal was seemingly more important for Southern and Eastern European participants compared to the other regions. CONCLUSION: The majority of older people with lived falls experience expressed an interest in a fall-prevention patient portal providing personalized treatment advice to prevent further falls. The results will be used to inform the development of a fall-prevention patient portal. The fall-prevention patient portal is intended to be used in addition to a consultation with a physician. Future research is needed to explore how to prevent falls in older patients who are not interested in a fall-prevention patient portal.

Risk factors for fracture in elderly men: a population-based prospective study.

SUMMARY: Risk factors for fractures were assessed in a random sample of 4,696 elderly men followed for 5.4 years. Results highlighted the importance of assessment of falls and dizziness as well as novel risk factors including frequent urination and erectile dysfunction. INTRODUCTION: Knowledge about risk factors for fracture in men is limited. The aim of this study was to evaluate factors potentially associated with fracture risk in men. METHODS: A questionnaire enquiring about potential risk factors for fractures in men was posted to a random sample of 9,314 men aged 60-74 years. A completed questionnaire was returned by 4,696 (50.4%). Follow-up on incident fractures over 5.4 years was performed using public registries. RESULTS: During the study, 203 individuals experienced a first clinical fracture, of which 85 patients were considered osteoporotic (9 in humerus, 10 vertebral, 32 in the hip and 34 in the forearm). Cox proportional hazard regression models were used to evaluate risk factors for any and osteoporotic fractures. The following variables were found to be associated with increased risk of any fracture in adjusted models family history of a hip fracture (HR; 95%CI: 1.56; 1.05-2.33), falls (2-4/year: 2.10; 1.35-3.27, >4/year: 2.46; 1.12-5.41, both compared to no falls), dizziness (2.36; 1.51-3.71), erectile dysfunction (1.41; 1.06-1.87) and frequent urination (2.06; 1.26-3.39). Similarly, falls (2.36; 1.45-3.86), dizziness (2.83; 1.52-5.25), erectile dysfunction (2.01; 1.30-3.09) and pulmonary illness (1.90; 1.03-3.53) were associated with increased risk of osteoporotic fractures in adjusted models. CONCLUSION: These results underline the importance of assessment of dizziness, falls and those with a family history of hip fracture. Frequent urination and erectile dysfunction were independently associated with increased fracture risk. Although the mechanism of association is unknown, these variables are likely to be indicators of frailty or hypogonadism.

Proceedings of the Rank Forum on Vitamin D.

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of 'optimal' concentration of serum 25(OH)D needs to define 'optimal' with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

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.

Effect of a 6-Month Brisk Walking Program on Walking Endurance in Sedentary and Physically Deconditioned Women Aged 60 or Older: A Randomized Trial.

BACKGROUND: Walking endurance is a predictor of healthy ageing. OBJECTIVE: To examine if a 6-month brisk walking program can increase walking endurance in sedentary and physically deconditioned older women. TRIAL DESIGN: Randomized controlled trial. SETTING: Women recruited from public meetings aimed at promoting physical activity in women aged 60 or older. SUBJECTS: 121 women aged 65.7 ± 4.3 years, with sedentary lifestyle (Physical Activity Questionnaire for the Elderly score < 9.4), and a 6-minute walking distance (6MWD) below normal value based on their gender, age, and body weight, and weight. METHODS: Women were randomly assigned to a 150 min/week brisk walking program (two supervised sessions and one session on their own per week) for six months (exercisers) (n=61) or a control group with physical activity allowed freely (n=60). OUTCOME: The primary outcome was relative change in 6MWD. RESULTS: 54/61 exercisers and 55/60 control subjects completed the program and data analysis was possible for 51 exercisers and 47 controls. At baseline, 6MWD was on average 23.1% and 22.5% below age-matched norms in exercisers and controls, respectively. Attendance rate for supervised sessions was 92% in exercisers. The 6MWD increased more significantly in exercisers than in controls (mean increase of 41.5% vs 11.0 %; p<0.0001). Over the 6-month program, 38 exercisers (74.5%) vs 5 controls (10.6%) had a 6MWD over the age-matched norm (p<0.0001). Exercisers with the highest tertile of 6MWD improvement (>46%) were those with baseline lowest values of 6MWD (p=0.001) and highest values of body mass index (BMI) (p<0.01). CONCLUSION: Present results support recommendation that brisk walking programs should be encouraged to improve walking endurance in physically deconditioned women aged 60 or older, especially in those with high BMI.

Reducing falls among older people in general practice: The ProAct65+ exercise intervention trial.

BACKGROUND: Falls are common in the older UK population and associated costs to the NHS are high. Systematic reviews suggest that home exercise and group-based exercise interventions, which focus on progressively challenging balance and increasing strength, can reduce up to 42% of falls in those with a history of falls. The evidence is less clear for those older adults who are currently at low risk of falls. AIM: ProAct65+, a large, cluster-randomised, controlled trial, investigated the effectiveness of a home exercise programme (Otago Exercise Programme (OEP)) and a group-based exercise programme (Falls Management Exercise (FaME)) compared to usual care (UC) at increasing moderate to vigorous physical activity (MVPA). This paper examines the trial's secondary outcomes; the effectiveness of the interventions at reducing falls and falls-related injuries. SETTING & PARTICIPANTS: 1256 community-dwelling older adults (aged 65+) were recruited through GP practices in two sites (London and Nottingham). Frequent fallers (≥3 falls in last year) and those with unstable medical conditions were excluded, as were those already reaching the UK Government recommended levels of physical activity (PA) for health. METHODS: Baseline assessment (including assessment of health, function and previous falls) occurred before randomisation; the intervention period lasted 24 weeks and there was an immediate post-intervention assessment; participants were followed up every six months for 24 months. Falls data were analysed using negative binomial modelling. OUTCOME MEASURES: Falls data were collected prospectively during the intervention period by 4-weekly diaries (6 in total). Falls recall was recorded at the 3-monthly follow-ups for a total of 24 months. Balance was measured at baseline and at the end of the intervention period using the Timed Up & Go and Functional Reach tests. Balance confidence (CONFbal), falls risk (FRAT) and falls self-efficacy (FES-I) were measured by questionnaire at baseline and at all subsequent assessment points. RESULTS: 294 participants (24%) reported one or two falls in the previous year. There was no increase in falls in either exercise group compared to UC during the intervention period (resulting from increased exposure to risk). The FaME arm experienced a significant reduction in injurious falls compared to UC (incidence rate ratio (IRR) 0.55, 95% CI 0.31, 0.96; p=0.04) and this continued during the 12 months after the end of the intervention (IRR 0.73, 95% CI 0.54, 0.99; p=0.05). There was also a significant reduction in the incidence of all falls (injurious and non-injurious) in the FaME arm compared with UC (IRR 0.74, 95% CI 0.55, 0.99; p=0.04) in the 12 month period following the cessation of the intervention. There was a non-significant reduction in the incidence of all falls in the OEP arm compared with UC (IRR 0.76, 95% CI 0.53, 1.09; p=0.14) in the 12 months following the cessation of the intervention. The effects on falls did not persist at the 24 months assessment in either exercise arm. However, when those in the FaME group who continued to achieve 150min of MVPA per week into the second post-intervention year were compared to those in the FaME group who did not maintain their physical activity, there was a significant reduction in falls incidence (IRR=0.49, 95% CI 0.30, 0.79; p=0.004). CONFbal was significantly improved at 12 months post intervention in both intervention arms compared with UC. There were no significant changes in any of the functional balance measures, FES-I or FRAT, between baseline and the end of the intervention period. CONCLUSION: Community-dwelling older adults who joined an exercise intervention (FaME) aimed at increasing MVPA did not fall more during the intervention period, fell less and had fewer injurious falls in the 12 months after cessation of the intervention. However, 24 months after cessation of exercise, the beneficial effects of FaME on falls reduction ceased, except in those who maintained higher levels of MVPA. OEP exercise appears less effective at reducing falls in this functionally more able population of older adults.

A Comprehensive Fracture Prevention Strategy in Older Adults: The European Union Geriatric Medicine Society (EUGMS) Statement.

Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.

A randomized trial of two etoposide schedules in small-cell lung cancer: the influence of pharmacokinetics on efficacy and toxicity.

PURPOSE: Etoposide is a schedule-dependent drug, as demonstrated by the superiority of 5 consecutive daily infusions over a continuous 24-hour infusion in patients with small-cell lung cancer. A randomized trial has therefore been conducted to compare an extended 8-day regimen with the 5-day schedule. PATIENTS AND METHODS: Ninety-four patients with small-cell lung cancer (35 limited disease, 59 extensive disease) were randomized to receive single-agent etoposide 500 mg/m2, either as 5 daily 2-hour infusions of 100 mg/m2 or as 8 daily 75-minute infusions of 62.5 mg/m2, both repeated every 3 weeks for six cycles. Single-agent carboplatin was administered at relapse in both arms of the study. Patients were stratified at randomization according to extent of disease and Karnofsky performance status (KPS). RESULTS: The overall response rate was 81% in the 5-day arm and 87% in the 8-day arm, with median survival durations of 7.1 and 9.4 months, respectively (no significant differences). The time over which plasma etoposide exceeded low plasma concentrations was significantly longer in patients who responded compared with patients who did not respond. This was most significant for time at concentrations greater than 1, 1.5, and 2 micrograms/mL. Hematologic toxicity was significantly worse in the 5-day arm of the study (cycle no. 1 nadir neutrophil count, 0.8 x 10(9)/L v 1.7 x 10(9)/L). Stepwise regression analysis found duration of exposure to plasma etoposide greater than 3 micrograms/mL to be predictive of nadir neutrophil count and duration of exposure to plasma etoposide greater than 2 micrograms/mL to be predictive of nadir WBC count. CONCLUSION: The 5-day and 8-day regimens had equivalent activity in small-cell lung cancer. A pharmacokinetic association between concentrations of etoposide and response and toxicity was found. Antitumor activity was associated with the maintenance of lower levels of etoposide than found to be associated with hematologic toxicity. This supports the hypothesis that the schedule of etoposide administration may affect efficacy and toxicity, and that prolonged exposure to low concentrations of etoposide may improve the therapeutic ratio for this drug.

Falls and health status in elderly women following first eye cataract surgery: a randomised controlled trial.

BACKGROUND/AIM: A third of elderly people fall each year. Poor vision is associated with increased risk of falls. The authors aimed to determine if first eye cataract surgery reduces the risk of falling, and to measure associated health gain. METHODS: 306 women aged over 70, with cataract, were randomised to expedited (approximately 4 weeks) or routine (12 months wait) surgery. Falls were ascertained by diary, with follow up every 3 months. Health status was measured after 6 months. RESULTS: Visual function improved in the operated group (corrected binocular acuity improved by 0.25 logMAR units; 8% had acuity worse than 6/12 compared with 37% of controls). Over 12 months of follow up, 76 (49%) operated participants fell at least once, and 28 (18%) fell more than once. 69 (45%) unoperated participants fell at least once, 38 (25%) fell more than once. Rate of falling was reduced by 34% in the operated group (rate ratio 0.66, 95% confidence interval 0.45 to 0.96, p = 0.03). Activity, anxiety, depression, confidence, visual disability, and handicap all improved in the operated group compared with the control group. Four participants in the operated group had fractures (3%), compared with 12 (8%) in the control group (p = 0.04). CONCLUSION: First eye cataract surgery reduces the rate of falling, and risk of fractures and improves visual function and general health status.

A population study of the screening potential of assessment of trabecular pattern of the femoral neck (Singh index): the Chingford Study.

The trabecular pattern of the femoral neck (Singh index) has been used as a measure of osteopenia and fracture risk but the value of this method is controversial. This study assessed the usefulness of the Singh index (SI) by using dual energy X-ray absorptiometry (DXA) as the "gold standard". 659 Caucasian women (45-70 years) from an age-sex register of a general practice had their femoral neck and lumbar spine bone densities measured by DXA and had antero-posterior hip X-rays performed which were then categorized into six osteopenia grades using the SI method. The intraobserver and interobserver reproducibility of this method was good (kappa = 0.64 and 0.61, respectively). The SI grades correlated significantly with body mass index (r = 0.35) and age (r = 0.17) (p < 0.001). The mean femoral neck and lumbar spine bone densities were significantly higher with increasing SI grade even after adjustment for age and body mass index (p < 0.001). The proportion of subjects below the fracture threshold (2 SD below mean peak bone mass) decreased with increasing SI grade, ranging from 100% in SI grade 2 to 16.8% in SI grade 6. There was, however, wide overlap of bone densities between the grades. Using the criteria "osteoporosis < or = SI grade 4", the sensitivity and specificity of the SI method diagnosing low bone mass was 35.1% and 90.0%, respectively. These data suggest that the SI is a reproducible tool which may detect differences in bone mass between populations or subgroups within populations, although caution should be used in classifying individual patients because of the wide variation in bone density. The method has a low sensitivity but a relatively high specificity in diagnosing low bone mass.