Frailty in younger adults in hospital.

BACKGROUND: Even though frailty has been extensively measured in the acute care setting, relatively little is known about the frailty of younger adult inpatients. AIM: This study aimed to measure frailty in a sample of hospitalized adults aged 18 years and over and to examine how frailty in younger adult inpatients differs from middle-aged and older adult inpatients. DESIGN: Secondary analyses of prospectively collected cohort data. METHODS: Research nurses assessed 910 patients at admission to four Australian hospitals using the interRAI Acute Care instrument. Comparison of frailty index (FI) scores and domains was conducted across three age groups: younger (18-49 years), middle-aged (50-69 years) and older adults (≥70 years). Multivariable logistic regression examined risk of prolonged length of stay and unfavourable discharge destination. RESULTS: Younger adults (n = 214; 23.5%) had a mean (SD) FI of 0.19 (0.10). Approximately 27% (n = 57) of younger adults were frail (FI > 0.25). Mood and behaviour, health symptoms and syndromes, nutrition and pain were the most frequently affected domains in younger adults and 50% had ≥3 comorbidities. Frailty increased the risk of long length of stay (odds ratio (OR) = 1.77, P < 0.001) but not the risk of an unfavourable discharge (OR = 1.40, P = 0.20) in younger adults. CONCLUSIONS: This study showed that frailty is prevalent in younger patients admitted to acute care and is associated with adverse outcomes. This study was a critical first step towards establishing an understanding of frailty in younger hospitalized adults.

Utility of PINP to monitor osteoporosis treatment in primary care, the POSE study (PINP and Osteoporosis in Sheffield Evaluation).

PURPOSE: In Sheffield (UK), we introduced the PINP monitoring algorithm for the management of osteoporosis treatment delivered in primary care. Our aims were to evaluate whether this algorithm was associated with better osteoporosis outcomes and was cost-effective compared to standard care. METHODS: Inclusion criteria were referral from Sheffield GPs, BMD scans performed between 2012 and 2013 and a report advising initiation of oral bisphosphonate and PINP monitoring. 906 patients were identified and retrospectively divided into Group A (intention to monitor, with baseline PINP, n = 588) and Group B (no intention to monitor, without baseline PINP, n = 318). The model described by Davis and colleagues was used to extrapolate life-time costs and quality-adjusted life-years (QALYs). RESULTS: No differences were found in baseline characteristics between groups (age, gender, BMI, BMD and major risk factors for fractures). More patients in Group A started oral treatment (77.4% vs 49.1%; p < 0.001), but there were no differences between groups in the presence of a gap in treatment >3 months or in treatment duration. Patients in Group A were more likely to have follow-up DXA scan at 4-6 years from baseline (46.9% vs 29.2%; p < 0.000) and had a greater increase in total hip BMD (+2.74% vs + 0.42%; p value = 0.003). Fewer new fractures occurred in Group A but this was not statistically significant, but the numbers of fractures were small. Patients in Group A were more likely to change management (p = 0.005) including switching to zoledronate (p = 0.03). The PINP measurement and increased prescribing in Group A resulted in increases in both costs (£30.19) and QALYs (0.0039) relative to Group B, giving an incremental cost effectiveness ratio (ICER) of £7660 in the probabilistic sensitivity analysis. CONCLUSIONS: Patients monitored with PINP are more likely to start oral bisphosphonate treatment, switch to zoledronate, have follow-up DXA scans and a greater increase of hip BMD. PINP monitoring has the potential to be cost-effective in a UK NHS setting given that interventions with an ICER under £20,000 are generally considered to be cost-effective.

The clinical utility of TRACP-5b to monitor anti-resorptive treatments of osteoporosis.

TRACP-5b can be used to monitor the response of treatments in osteoporosis. We investigated the effect of feeding on levels of TRACP-5b and how these markers perform in a clinical setting. After feeding, there was no effect on levels TRACP-5b. It has similar diagnostic accuracy to CTX and PINP. INTRODUCTION: Bone turnover markers (BTMs) can be used to monitor response to osteoporosis treatment. However, some are affected by food intake and are not suitable to measure in a clinical setting. An assay is available which is capable of detecting the active isoform 5b of tartrate resistance acid phosphatase (TRACP-5b) and it may have minimal biological variation. Our aims were to investigate the effect of feeding on levels of TRACP-5b and compare this to CTX and PINP and then to compare the diagnostic accuracy of TRACP-5b to CTX and PINP in patients with osteoporosis given commonly used treatments. METHODS: Eighteen patients were recruited to investigate the effect of feeding on BTMs. Ninety-seven patients (74 females and 23 males) receiving 5 mg annual intra-venous zoledronate (mean age 70) and 97 patients receiving no treatment were recruited as group-matched controls. Sixteen patients receiving 60 mg subcutaneous denosumab every 6 months, (mean age 76) and 16 matched controls were recruited. Seventy-six patients were receiving oral bisphosphonates: 70 mg alendronate weekly, 35 mg risedronate and 150 mg monthly ibandronate (4%). Thirty of these patients had BMD measured at the total hip and lumbar spine. An estimate of compliance was not determined. Eighty patients receiving no treatment were recruited as group-matched controls. TRACP-5b (ELISA, Nittobo) and CTX and PINP were measured in serum in the non-fasting state between 0800 and 1700. RESULTS: After feeding, there was no effect on levels TRACP-5b and significant reductions in CTX and PINP, 29% and 10%, respectively (p < 0.001). In the zoledronate and denosumab groups, there were no differences in the areas under the curves (AUCs) between TRACP-5b, PINP and CTX. In the oral bisphosphonates group, the AUCs between TRACP-5b and PINP and TRACP-5b and CTX were significantly different, p < 0.01 and p = 0.001, respectively. TRACP-5b was negatively correlated with BMD. CONCLUSION: TRACP-5b is not affected by food intake, unlike CTX and PINP. All three BTMs correlate with change in BMD at the lumbar spine and total hip. TRACP-5b has similar diagnostic accuracy to CTX and PINP with commonly used treatments for osteoporosis with the exception of oral bisphosphonate therapy.

Evaluation of estimated glomerular function (eGFR) versus creatinine clearance (CrCl) to predict acute kidney injury when using zoledronate for the treatment of osteoporosis.

Zoledronate could be contributing to the development of acute kidney injury in a small number of patients. Since estimated glomerular function (eGFR) is simpler to obtain and at least as good a predictor as creatinine clearance (CrCl), it should be used in everyday practice. INTRODUCTION: Zoledronate is widely used for the treatment of osteoporosis. A potential side effect is acute kidney injury (AKI). Advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) in 2019 stated that CrCl and not estimated glomerular filtration rate (eGFR) should be used and that treatment should not be given if CrCl < 35 ml/min. The objective of this study was to compare our current method of assessing renal function (eGFR) with the method proposed by the MHRA (CrCl) for predicting AKI after zoledronate infusions. METHODS: The evaluation was performed at the Metabolic Bone Centre in Sheffield Teaching Hospitals, UK. Data on all the patients who had zoledronate from 1/09/2015 to 1/10/2020 were included. RESULTS: Data on 4405 patients were retrieved (total number of infusions 7660). Creatinine in the 14 days post-infusion was available for a total of 969 infusions and AKI was observed within 14 days following 45 infusions (4.6%). One patient died due to pneumonia. One patient needed continued haemodialysis. Severe AKI (threefold in creatinine and/or eGFR < 15 ml/min/173 m2) was observed within 1 year following 24 infusions. If the MHRA recommendations had been followed, 996 infusions with baseline CrCl < 35 ml/min would not have been given. Of these, follow-up data on serum creatinine within 14 days were available for 142 infusions, showing AKI in only four (2.8%). Logistic regression showed that both CrCl and eGFR were significant factors in predicting AKI within 14 days, but that the current recommended cut-off of CrCl 35 ml/min had poor sensitivity. CONCLUSION: Since eGFR is at least as good a predictor of AKI as CrCl, and permits the treatment of more patients at high fracture risk, we recommend that eGFR is used to determine renal function for zoledronate treatment. We suggest that the infusion is given over 30 min in patients with eGFR < 50 ml/min/1.73 m2.

Frailty: A cost incurred by reproduction?

Evolutionary theories of senescence, such as the 'disposable soma' theory, propose that natural selection trades late survival for early fecundity. 'Frailty', a multidimensional measure of health status, may help to better define the long-term consequences of reproduction. We examined the relationship between parity and later life frailty (as measured by the Frailty Index) in a sample of 3,534 adults aged 65 years and older who participated in the English Longitudinal Study of Ageing. We found that the most parous adults were the most frail and that the parity-frailty relationship was similar for both sexes. Whilst this study provided some evidence for a 'parity-frailty trade-off', there was little support for our hypothesis that the physiological costs of childbearing influence later life frailty. Rather, behavioural and social factors associated with rearing many children may have contributed to the development of frailty in both sexes.

Quantitative computed tomography discriminates between postmenopausal women with low spine bone mineral density with vertebral fractures and those with low spine bone mineral density only: the SHATTER study.

Lumbar spine volumetric bone mineral density (BMD) measured using quantitative computed tomography (QCT) can discriminate between postmenopausal women with low areal BMD with and without vertebral fractures. QCT provides a 3D measure of BMD, excludes the vertebral posterior elements and accounts for bone size. This knowledge could contribute to effective treatment targeting of patients with low BMD. INTRODUCTION: We evaluated the ability of lumbar spine bone mineral apparent density (BMAD), trabecular bone score (TBS) and volumetric bone mineral density (vBMD) to discriminate between postmenopausal women with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) with and without vertebral fractures. The discriminatory ability of lumbar spine aBMD was compared with that of BMAD, TBS and vBMD. METHODS: We studied three groups of postmenopausal women, i.e. group 1, aBMD T-score < - 1.0 and ≥ 1 vertebral fracture (n = 39); group 2, aBMD T-score < - 1.0 and no vertebral fracture, age- and aBMD-matched to group 1 (n = 34); group 3, aBMD score > - 1 and no vertebral fracture, age-matched to group 1 (n = 37). Lumbar spine aBMD was measured by DXA. BMAD was calculated using the DXA scan results. TBS was derived following DXA scan image reanalysis. Lumbar spine vBMD was assessed by quantitative computed tomography and Mindways Pro software. Differences in variables between groups 1, 2 and 3 were examined using general linear univariate modelling approaches. Area under the receiver operating characteristic (ROC) curve was calculated for BMAD, TBS and vBMD to determine the ability of lumbar spine measurement variables to discriminate between group 1 and group 2. A comparison of ROCs was performed. RESULTS: Lumbar spine BMAD and TBS measurement variables were similar for groups 1 and 2. However, vBMD was significantly lower in group 1 and could discriminate between those women with low aBMD with (group 1) and without vertebral fractures (group 2). CONCLUSIONS: We conclude that lumbar spine vBMD may discriminate well between postmenopausal women with low aBMD with and without vertebral fractures as it provides a 3D measure of bone mineral density, excludes the posterior elements of the vertebrae and takes into account bone size. A unique feature of the SHATTER study is that groups 1 and 2 were matched for aBMD, thus our study findings are independent of aBMD. Furthermore, we observed that neither BMAD nor TBS could distinguish between women with low aBMD with and without vertebral fractures. The knowledge gained from the SHATTER study will influence clinical and therapeutic decision-making, thereby optimising the care of patients with and without vertebral and other fragility fractures.

The effect of bisphosphosphonates on bone turnover and bone balance in postmenopausal women with osteoporosis: The T-score bone marker approach in the TRIO study.

Postmenopausal osteoporosis is characterised by increased bone turnover and an imbalance between bone resorption and formation. Bisphosphonate treatment reduces bone turnover but their effect on bone balance is yet to be fully investigated. Using the T-score approach our aims were to: i) investigate the effects of oral nitrogen-containing bisphosphonates on bone balance and turnover in postmenopausal women with osteoporosis and ii) determine the relationship of the change in bone balance and turnover with the change in BMD at the lumbar spine and total hip. Women were recruited, mean age 67 years, and randomised to receive: ibandronate (n = 55, 150 mg/month), alendronate (n = 54, 70 mg/week) or risedronate (n = 56, 35 mg/week). They also received calcium and vitamin D daily. A fasting serum sample was collected at baseline and weeks 1, 2, 4, 12, 13, 48 and 96. The control group were 226 healthy premenopausal women receiving no treatments. PINP and CTX were measured using the iSYSIDS analyser and BMD (in g/cm2) of the lumbar spine and total hip were measured by DXA (Hologic Inc). PINP and CTX values were log10-transformed and normalised. T-scores were calculated using the mean and standard deviation from the premenopausal group. Bone turnover and bone balance were calculated from the T-scores. Mean levels (95% CI) of balance and turnover are shown in the table. The change in turnover at weeks 4, 12 and 48 was inversely correlated with the change in lumbar spine and total hip BMD at weeks 48 and 96, (p < .01 to p < .001). The change in balance at week 4 positively correlated with the change in total hip BMD at weeks 48, (p < .01). Bisphosphonates resulted in an initial positive balance and a reduction in turnover. Some of these changes were associated with increases in BMD. Bone turnover is a better predictor of BMD than bone balance.

Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis.

Bone markers may be useful to monitor response to treatment withdrawal in osteoporosis. We used two criteria for investigating the change in BTMs after withdrawal of bisphosphonate treatment. A larger increase in BTMs was associated with greater bone loss. Bone markers may be useful in monitoring of patients taking a pause from treatment. INTRODUCTION: Measurement of bone turnover markers (BTMs) may be useful to monitor offset of treatment with bisphosphonates (BP) in osteoporosis. We assessed the effect of withdrawal of BP treatment by comparing the changes in BTMs and total hip (TH) bone density (BMD). METHODS: We studied postmenopausal osteoporotic women who had completed a randomised study of three oral BPs. After 2 years of treatment, participants with BMD T-score > - 2.5 and in whom it was considered clinically appropriate to discontinue treatment, were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs (CTX and PINP) with offset being defined by two criteria: (1) an increase greater than the least significant change (LSC) and (2) an increase above the reference mean value. RESULTS: Fifty women completed the study. At 48 weeks after stopping BPs, CTX was greater than the LSC for 66% of women and PINP 72%; CTX was above the reference mean for 64% of women and PINP 42%. The decrease in THBMD was greater for women with the largest increase in BTM compared to those with continued suppression (mean difference for CTX was - 2.98%, 95%CI - 4.75 to - 1.22, P < 0.001, PINP - 2.25%, 95% CI - 4.46 to - 0.032, P = 0.046). CONCLUSION: The measurement of BTM after withdrawal of BPs is potentially useful to evaluate patients that are taking a pause from treatment. An increase in BTMs more than the LSC and/or reference mean reflects loss of treatment effect and identifies patients that are likely to have a decrease in BMD. Such changes could provide an indication for reintroduction of treatment.

Validation of a frailty index in older cancer patients with solid tumours.

BACKGROUND: Frailty is an indicator of physiological reserve in older people. In non-cancer settings, frailty indices are reliable predictors of adverse health outcomes. The aims of this study were to 1) derive and validate a frailty index (FI) from comprehensive geriatric assessment (CGA) data obtained in the solid tumour chemotherapy setting, and 2) to explore whether the FI-CGA could predict chemotherapy decisions and survival in older cancer patients with solid tumours. METHODS: Prospective cohort study of a consecutive series sample of 175 cancer patients aged 65 and older with solid tumours. A frailty index was calculated using an accumulated deficits model, coding items from the comprehensive geriatric assessment tool administered prior to chemotherapy decision-making. The domains of physical and cognitive functioning, nutrition, mood, basic and instrumental activities of daily living, and comorbidities were incorporated as deficits into the model. RESULTS: The FI-CGA had a right-skewed distribution, with median (interquartile range) of 0.27 (0.21-0.39). The 99% limit to deficit accumulation was below the theoretical maximum of 1.0, at 0.75. The FI-CGA was significantly related (p < 0.001) to vulnerability as assessed by the Vulnerable Elders Survey-13 and to medical oncologists' assessments of fitness or vulnerability to treatment. Baseline frailty as determined by the FI-CGA was also associated with treatment decisions (Treatment Terminated, Treatment Completed, No Planned Treatment) (p < 0.001), with the No Planned Treatment group significantly frailer than the other two groups. CONCLUSION: The FI-CGA is a potentially useful adjunct to cancer clinical decision-making that could predict chemotherapy outcomes in older patients with solid tumours.

Do health assets have a protective effect for hospitalized frail older adults?

BACKGROUND: Although increasing frailty is predictive of increased mortality and length of stay for hospitalized older adults, this approach ignores health assets that individuals can utilize to recover following hospital admission. AIM: To examine whether health assets mitigate the effect of frailty on outcomes for older adults admitted to hospital. DESIGN: Patients of 1418 aged ≥ 70 years admitted to 11 hospitals in Australia were evaluated at admission using the interRAI assessment system for Acute Care, which surveys a large number of domains, including cognition, communication, mood and behaviour, activities of daily living, continence, nutrition, skin condition, falls and medical diagnosis. METHODS: The data set was interrogated for potential health assets and a multiple logistic regression adjusted for frailty index, age and gender as covariates was performed for the outcomes mortality, length of stay, re-admission and new need for residential care. RESULTS: Inpatient mortality was 3% and 4.5% of patients died within 28 days of discharge. Median length of stay was 7 days (IQR 4-11). In multivariate analysis that includes frailty, being able to walk further [OR 0.08 (0.01-0.63)], ability to leave the house [OR 0.35 (0.17-0.74)] and living alone [OR 0.28 (0.10-0.79)] were protective against mortality. The presence of a support person was associated with a decreased length of stay [OR 0.14 (0.08-0.25)]. CONCLUSION: The inclusion of health assets in predictive models can improve prognostication and highlights potential interventions to improve outcomes for hospitalized older adults.

The Utility of the Frailty Index in Clinical Decision Making.

Using clinical vignettes, this study aimed to determine if a measure of patient frailty would impact management decisions made by geriatricians regarding commonly encountered clinical situations. Electronic surveys consisting of three vignettes derived from cases commonly seen in an acute inpatient ward were distributed to geriatricians. Vignettes included patients being considered for intensive care treatment, rehabilitation, or coronary artery bypass surgery. A frailty index was generated through Comprehensive electronic Geriatric Assessment. For each vignette, respondents were asked to make a recommendation for management, based on either a brief or detailed amount of clinical information and to reconsider their decision after the addition of the frailty index. The study suggests that quantification of frailty might aid the clinical judgment now employed daily to proceed with usual care, or to modify it based on the vulnerability of the person to whom it is aimed.

Teriparatide treatment exerts differential effects on the central and peripheral skeleton: results from the MOAT study.

The central and peripheral skeleton was characterised using imaging techniques during 104 weeks of teriparatide treatment. Teriparatide exerts differential effects on the central and the peripheral skeleton. Overall, we did not observe a change in total body bone mineral. Our conclusions are constrained by the study limitations. INTRODUCTION: Teriparatide stimulates bone formation and resorption and therefore can cause bone gain and loss. We simultaneously characterised the central and peripheral skeleton using imaging techniques to better understand the mechanism of action of teriparatide. METHODS: Postmenopausal, osteoporotic women (n = 20, 65.4 ± 5.5 years) were recruited into a 104-week study of teriparatide. Imaging techniques included DXA, quantitative computed tomography (QCT), and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Total lumbar spine areal bone mineral content (aBMC) (+ 11.2%), total lumbar spine areal bone mineral density (aBMD) (+ 8.1%), subregional thoracic spine aBMD (+ 7.5%), lumbar spine aBMC (+ 23.5%), lumbar spine aBMD (+ 11.9%), pelvis aBMC (+ 9.3%), and pelvis aBMD (+ 4.3%) increased. However, skull aBMC (- 5.0%), arms aBMC (- 5.1%), legs aBMC (- 2.9%), and legs aBMD (- 2.5%) decreased. Overall, we did not observe a change in total body bone mineral. Increases in L1-L3 volumetric BMD (vBMD) (+ 28.5%) occurred but there was no change in total proximal femur vBMD. Radius and tibia cortical vBMD (- 3.3 and - 3.4%) and tissue mineral density (- 3.2 and - 3.8%) decreased and there was an increase in porosity (+ 21.2 and + 10.3%). Tibia, but not radius, trabecular inhomogeneity (+ 3.2%), and failure load (+ 0.2%) increased, but cortical thickness (- 3.1%), area (- 2.9%), and pore volume (- 1.6%) decreased. CONCLUSIONS: Teriparatide exerts differential effects on the central and the peripheral skeleton. Central trabecular vBMD (L1-L3) is improved, but there is a concomitant decrease in peripheral cortical vBMD and an increase in porosity. Overall, we did not observe a change in total body bone mineral. We acknowledge that our conclusions may be speculative and are constrained by the technical limitations of the imaging techniques used, the lack of a control group, and the small sample size studied.

Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density.

The antiresorptive potency varies between different bisphosphonates. We investigated the effect of stopping oral bisphosphonate treatment for postmenopausal osteoporosis (ibandronate, alendronate, risedronate) on BTMs and BMD. After stopping treatment, all three groups showed an increase in BTMs and a decrease in hip BMD; however, none returned to pre-treatment baseline values. INTRODUCTION: Bisphosphonates (BPs) continue to suppress bone turnover markers (BTMs) after treatment has stopped, leading to the suggestion that a pause in treatment could be considered for low-risk patients. Indirect comparisons suggest that after cessation of treatment, the effects on bone may differ between drugs. We investigated the effects of stopping oral BP treatments for postmenopausal osteoporosis on BTMs and bone mineral density (BMD). METHODS: We studied postmenopausal osteoporotic women who had previously taken part in a 2-year randomised study of three oral BPs (ibandronate, alendronate, or risedronate). At the end of the study, women with hip BMD T-score > - 2.5 and considered clinically appropriate to discontinue treatment were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs, and BMD was measured by dual-energy X-ray absorptiometry. RESULTS: All BTMs increased after treatment withdrawal but remained below the pre-treatment baseline with less suppression of BTMs for the risedronate group compared to alendronate and ibandronate up to 48 weeks. There was no difference between the BP groups 96 weeks after stopping treatment. The change in BMD during the 96 weeks after stopping treatment was - 1.6% (95% CI - 1.9 to - 1.2, P < 0.001) for the total hip and - 0.6% (95% CI - 1.1 to - 0.2, P = 0.17) at the lumbar spine with no difference between the three BP groups (P = 0.85 and P = 0.48, respectively). CONCLUSION: For all treatment groups, there was an increase in BTMs and a decrease in hip BMD after stopping BPs for 2 years; however, none returned to pre-treatment baseline values.

Perioperative assessment of older surgical patients using a frailty index-feasibility and association with adverse post-operative outcomes.

This study aimed to examine the feasibility of using a frailty index (FI) based on comprehensive geriatric assessment (CGA), to assess the level of frailty in older surgical patients preoperatively and to evaluate the association of FI-CGA with poorer postoperative outcomes. Two hundred and forty-six patients aged ≥70 years undergoing intermediate- to high-risk surgery in a tertiary hospital were recruited. Frailty was assessed using a 57-item FI-CGA form, with fit, intermediate frail, and frail patients defined as FI ≤0.25, >0.25 to 0.4, and >0.4, respectively. Adverse outcomes were ascertained at 30 days and 12 months post-surgery. Logistic regression models assessed the relationship between FI and adverse outcomes, adjusting for age, gender and acuity of surgery. The mean age of the participants was 79 years (standard deviation [SD] 6.5%), 52% were female, 91% were admitted from the community, 43% underwent acute surgery, and 19% were assessed as frail. The FI-CGA form was reported as being easy to apply, with a low patient refusal rate (2.2%). The majority of items were easy to rate, although inter-rater reliability was not tested. In relation to outcomes, greater frailty was associated with increased 12-month mortality (6.4%, 15.6%, and 23% for fit, intermediate frail, and frail patients respectively, P=0.01) and 12-month hospital readmissions (33.9%, 48.9%, and 60% respectively, P=0.004). There were no statistically significant differences between fit, intermediate frail, and frail groups in perioperative adverse events (17.4%, 23.3%, and 19.1% respectively, P=0.577) or 30-day postoperative complications (35.8%, 47.8%, and 46.8% respectively, P=0.183). Our findings suggest that it is feasible to use the FI-CGA to assess frailty preoperatively, and that using the FI-CGA may identify patients at high risk of adverse long-term outcomes.

Sex differences in frailty: A systematic review and meta-analysis.

BACKGROUND: It is a well-described clinical phenomenon that females live longer than males, yet tend to experience greater levels of co-morbidity and disability. Females can therefore be considered both more frail (because they have poorer health status) and less frail (because they have a lower risk of mortality). This systematic review aimed to determine whether this ageing paradox is demonstrated when the Frailty Index (FI) is used to measure frailty. METHODS: Medline, EMBASE and CINAHL databases were searched for observational studies that measured FI and mortality in community-dwellers over 65years of age. In five-year age groups, meta-analysis determined the sex differences in mean FI (MD=mean FIfemale-mean FImale) and mortality rate. RESULTS: Of 6482 articles screened, seven articles were included. Meta-analysis of data from five studies (37,426 participants) found that MD values were positive (p<0.001; MD range=0.02-0.06) in all age groups, indicating that females had higher FI scores than males at all ages. This finding was consistent across individual studies. Heterogeneity was high (I2=72.7%), reflecting methodological differences. Meta-analysis of mortality data (13,127 participants) showed that male mortality rates exceeded female mortality rates up until the 90 to 94-years age group. Individual studies reported higher mortality for males at each level of FI, and higher risk of death for males when controlling for age and FI. CONCLUSIONS: The pattern of sex differences in the FI and mortality of older adults was consistent across populations and confirmed a 'male-female health-survival paradox'.

Frailty and post-operative outcomes in older surgical patients: a systematic review.

BACKGROUND: As the population ages, increasing numbers of older adults are undergoing surgery. Frailty is prevalent in older adults and may be a better predictor of post-operative morbidity and mortality than chronological age. The aim of this review was to examine the impact of frailty on adverse outcomes in the 'older old' and 'oldest old' surgical patients. METHODS: A systematic review was undertaken. Electronic databases from 2010 to 2015 were searched to identify articles which evaluated the relationship between frailty and post-operative outcomes in surgical populations with a mean age of 75 and older. Articles were excluded if they were in non-English languages or if frailty was measured using a single marker only. Demographic data, type of surgery performed, frailty measure and impact of frailty on adverse outcomes were extracted from the selected studies. Quality of the studies and risk of bias was assessed by the Epidemiological Appraisal Instrument. RESULTS: Twenty-three studies were selected for the review and they were assessed as medium to high quality. The mean age ranged from 75 to 87 years, and included patients undergoing cardiac, oncological, general, vascular and hip fracture surgeries. There were 21 different instruments used to measure frailty. Regardless of how frailty was measured, the strongest evidence in terms of numbers of studies, consistency of results and study quality was for associations between frailty and increased mortality at 30 days, 90 days and one year follow-up, post-operative complications and length of stay. A small number of studies reported on discharge to institutional care, functional decline and lower quality of life after surgery, and also found a significant association with frailty. CONCLUSION: There was strong evidence that frailty in older-old and oldest-old surgical patients predicts post-operative mortality, complications, and prolonged length of stay. Frailty assessment may be a valuable tool in peri-operative assessment. It is possible that different frailty tools are best suited for different acuity and type of surgical patients. The association between frailty and return to pre-morbid function, discharge destination, and quality of life after surgery warrants further research.

The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis: The TRIO study.

Bisphosphonates are used to treat bone disease characterised by increased bone resorption by inhibiting the activity of mature osteoclasts, resulting in decreased bone turnover. Bisphosphonates may also reduce the population of osteoclast precursor cells. Our aims were to investigate the effect of bisphosphonates on i) osteoclast precursor cells and ii) circulating cytokine and cytokine receptor in postmenopausal women with osteoporosis compared with healthy premenopausal women. Participants were 62 postmenopausal women (mean age 66) from a 48-week parallel group trial of bisphosphonates. They received ibandronate 150mg/month (n=22), alendronate 70mg/week (n=19) or risedronate 35mg/week (n=21). Fasting blood was collected at baseline, weeks 1 and 48. At baseline, blood was also collected from 25 healthy premenopausal women (mean age 37) to constitute a control group. Peripheral blood mononuclear cells were extracted and stained for CD14, M-CSFR, CD11b and TNFRII receptors. Flow cytometry was used to identify cells expressing CD14+ and M-CSFR+ or CD11b+ or TNFRII+. RANKL and OPG were measured to evaluate potential mediation of the bisphosphonate effect. After 48weeks of treatment, there was a decrease in the percentage of cells expressing M-CSFR and CD11b receptors by 53% and 49% respectively (p<0.01). Cells expressing M-CSFR and CD11b were decreased with ibandronate and risedronate after 48weeks to the lower part of the premenopausal reference interval. These effects were not significantly different between each of the treatment groups. There was no significant effect on RANKL and OPG throughout the study period. Bisphosphonates inhibit bone resorption in the short-term by direct action on mature osteoclasts. There is also a later effect mediated in part by a reduction in the population of circulating osteoclast precursors.

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia.

UNLABELLED: We used two methods of identifying women who reached the target for raloxifene treatment with bone turnover markers. Both approaches identified women that responded to treatment but did not fully agree and may be complementary. INTRODUCTION: The change in bone turnover markers (BTMs) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene. METHODS: Fifty postmenopausal osteopenic women (age 51-72 years) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40 years). Bone mineral density (BMD) was measured at the spine and hip. RESULTS: There was a decrease in BTM in response to raloxifene treatment, percentage change at 12 weeks: C terminal telopeptide of type I collagen (CTX) -39 % (95 % CI -48 to -28) and N terminal propeptide of type I procollagen (PINP) -32 % (95 % CI -40 to -23) P < 0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was as follows: CTX 38 % and PINP 52 % and at 48 weeks CTX 60 % and PINP 65 %. For the RI approach, the proportion of women classified as responding to treatment at 12 weeks was CTX and PINP 38 % and at 48 weeks CTX 40 % and PINP 45 %. There was a significant difference in the change in spine BMD in the raloxifene-treated group compared to the no-treatment group at week 48: difference 0.031 g/cm(2) (95 % CI 0.016 to 0.046, P < 0.001). CONCLUSIONS: The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response, but the two approaches do not fully overlap and may be complementary.