Confounding factors of the expression of mTBI biomarkers, S100B, GFAP and UCH-L1 in an aging population.

OBJECTIVES: To evaluate some confounding factors that influence the concentrations of S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L-1 (UCH-L1) in older individuals. Indeed, recent guidelines have proposed the combined use of S100B and the "GFAP-UCH-L1" mTBI test to rule out mild traumatic brain injuries (mTBI). As older adults are the most at risk of mTBI, it is particularly important to understand the confounding factors of those mTBI rule-out biomarkers in aging population. METHODS: The protein S100B and the "GFAP and UCH-L1" mTBI test were measured using Liaison XL (Diasorin) and Alinity I (Abbott), respectively, in 330 and 341 individuals with non-suspected mTBI from the SarcoPhAge cohort. RESULTS: S100B, GFAP and UCH-L1 were all significantly correlated with renal function whereas alcohol consumption, Geriatric Depression Score (GDS), smoking habits and anticoagulant intake were not associated with any of these three biomarkers. Body mass index (BMI) and age were associated with GFAP and UCH-L1 expression while sex and mini-mental state examination (MMSE) were only associated with GFAP. According to the manufacturer's cut-offs for mTBI rule-out, only 5.5 % of participants were positive for S100B whereas 66.9 % were positive for the "GFAP-UCH-L1" mTBI test. All positive "GFAP-UCH-L1" mTBI tests were GFAP+/UCH-L1-. Among individuals with cystatin C>1.55 mg/L, 25 % were positive for S100B while 90 % were positive for the mTBI test. CONCLUSIONS: Our data show that confounding factors have different impacts on the positivity rate of the "GFAP-UCH-L1" mTBI test compared to S100B.

Muscle parameters in fragility fracture risk prediction in older adults: A scoping review.

Half of osteoporotic fractures occur in patients with normal/osteopenic bone density or at intermediate or low estimated risk. Muscle measures have been shown to contribute to fracture risk independently of bone mineral density. The objectives were to review the measurements of muscle health (muscle mass/quantity/quality, strength and function) and their association with incident fragility fractures and to summarize their use in clinical practice. This scoping review follows the PRISMA-ScR guidelines for reporting. Our search strategy covered the three overreaching concepts of 'fragility fractures', 'muscle health assessment' and 'risk'. We retrieved 14 745 references from Medline Ovid SP, EMBASE, Web of Science Core Collection and Google Scholar. We included original and prospective studies on community-dwelling adults aged over 50 years that analysed an association between at least one muscle parameter and incident fragility fractures. We systematically extracted 17 items from each study, including methodology, general characteristics and results. Data were summarized in tables and graphically presented in adjusted forest plots. Sixty-seven articles fulfilled the inclusion criteria. In total, we studied 60 muscle parameters or indexes and 322 fracture risk ratios over 2.8 million person-years (MPY). The median (interquartile range) sample size was 1642 (921-5756), age 69.2 (63.5-73.6) years, follow-up 10.0 (4.4-12.0) years and number of incident fragility fractures 166 (88-277). A lower muscle mass was positively/not/negatively associated with incident fragility fracture in 28 (2.0), 64 (2.5) and 10 (0.2 MPY) analyses. A lower muscle strength was positively/not/negatively associated with fractures in 53 (1.3), 57 (1.7 MPY) and 0 analyses. A lower muscle function was positively/not/negatively associated in 63 (1.9), 45 (1.0 MPY) and 0 analyses. An in-depth analysis shows how each single muscle parameter was associated with each fragility fractures subtype. This review summarizes markers of muscle health and their association with fragility fractures. Measures of muscle strength and function appeared to perform better for fracture risk prediction. Of these, hand grip strength and gait speed are likely to be the most practical measures for inclusion in clinical practice, as in the evaluation of sarcopenia or in further fracture risk assessment scores. Measures of muscle mass did not appear to predict fragility fractures and might benefit from further research, on D3-creatine dilution test, lean mass indexes and artificial intelligence methods.

Comparison of the cost-effectiveness of sequential treatment with abaloparatide in US men and women at very high risk of fractures.

BACKGROUND: Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. AIMS: This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ - 2.5 and a recent fracture). METHODS: A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). RESULTS: From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. DISCUSSION: Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. CONCLUSIONS: Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

Sarcopenia and health-related quality of life: A systematic review and meta-analysis.

The decrease of physical abilities and functional decline that can be caused by musculoskeletal conditions such as sarcopenia, can lead to higher levels of dependency and disability. Therefore, it may influence patient reported outcome measures (PROM), such as the health-related quality of life (HRQoL). The purpose of this systematic review and meta-analysis is to provide a comprehensive overview of the relationship between sarcopenia and HRQoL. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed throughout the whole process of this work. A protocol was previously published on PROSPERO. The electronic databases MEDLINE, Scopus, Allied and Complementary Medicine (AMED), EMB Review - ACP Journal Club, EBM Review - Cochrane Central of Register of Controlled Trials and APA PsychInfo were searched until October 2022 for observational studies reporting a HRQoL assessment in both sarcopenic and non-sarcopenic individuals. Study selection and data extraction were carried out by two independent researchers. Meta-analysis was performed using a random effect model, reporting an overall standardized mean difference (SMD) and its 95% confidence interval (CI) between sarcopenic and non-sarcopenic individuals. Study quality was measured using the Newcastle-Ottawa Scale and the strength of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. The search strategy identified 3725 references from which 43 observational studies were eligible and included in this meta-synthesis study. A significantly lower HRQoL was observed for sarcopenic individuals compared with non-sarcopenic ones (SMD -0.76; 95% CI -0.95; -0.57). Significant heterogeneity was associated with the model (I2  = 93%, Q test P-value <0.01). Subgroup analysis showed a higher effect size when using the specific questionnaire SarQoL compared with generic questionnaires (SMD -1.09; 95% CI -1.44; -0.74 with the SarQoL versus -0.49; 95% CI -0.63; -0.36 with generic tools; P-value for interaction <0.01). A greater difference of HRQoL between sarcopenic and non-sarcopenic was found for individuals residing in care homes compared with community-dwelling individuals (P-value for interaction <0.001). No differences were found between age groups, diagnostic techniques, and continents/regions. The level of evidence was rated as moderate using the GRADE assessment. This systematic review and meta-analysis combining 43 observational studies shows that HRQoL is significantly reduced in sarcopenic patients. The use of disease-specific HRQoL instruments may better discriminate sarcopenic patients with respect to their quality of life.

An update on the use of conventional and biological disease-modifying anti-rheumatic drugs in hand osteoarthritis.

Osteoarthritis (OA) is a highly prevalent condition worldwide associated with pain, progressive disability, reduced participation in social activities, and impaired quality of life. Despite its growing burden, the therapeutic options are still limited and almost exclusively addressed to symptoms' management, while no disease-modifying OA drugs able to prevent or retard disease progression are actually available. For these reasons, in the last decades, relevant efforts to find new potential therapeutic targets in OA have been made and a number of existing conventional and biological disease-modifying anti-rheumatic drugs (DMARDs), including hydroxychloroquine (HCQ), methotrexate (MTX), tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 inhibitors, commonly used to treat inflammatory rheumatic diseases, have been repurposed for the treatment of OA and explored also in hand osteoarthritis (HOA). The current narrative review was aimed to provide a comprehensive and updated understanding of the possibilities and the criticisms related to the treatment of HOA with conventional and biological DMARDs. Unfortunately, therapy with conventional and biologic drugs in HOA has not achieved the expected success, despite a rationale for their use exists. Thus, our findings outline the urgent need to enhance the exploration of HOA basic molecular mechanisms to find new potential therapeutic targets, personalized for each patient, and appropriate for the different subsets of HOA and for the different phases of disease.

Sarcopenia is associated with a greater risk of polypharmacy and number of medications: a systematic review and meta-analysis.

Polypharmacy in older adults is associated with multiple negative consequences that may affect muscular function, independently from the presence of medical conditions. The aim of this systematic review and meta-analysis was to investigate the association of sarcopenia with polypharmacy and higher number of medications. A systematic literature search of observational studies using PubMed, Web of Science, Scopus and Cochrane Library databases was conducted from inception until June 2022. To determine if sarcopenia is associated with a higher risk of polypharmacy and increased number of medications, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42022337539). Twenty-nine studies were included in the systematic review and meta-analysis. Sarcopenia was associated with a higher prevalence of polypharmacy (odds ratio [OR]: 1.65, 95% confidence interval [CI] [1.23, 2.20], I2  = 84%, P < 0.01) and higher number of medications (mean difference: 1.39, 95% CI [0.59, 2.19], I2  = 95%, P < 0.01) compared with individuals without sarcopenia. Using meta-regression, a high variance was observed due to different populations (i.e., community-dwelling, nursing home residents, inpatients, outpatients) for both outcomes of polypharmacy (r = -0.338, SE = 0.1669, 95% CI [-0.67, -0.01], z = -2.03, P = 0.04) and number of medications (r = 0.589, SE = 0.2615, 95% CI [0.08, 1.10], z = 2.25, P = 0.02). This systematic review and meta-analysis reported a significantly increased risk of polypharmacy and higher number of medications in people with sarcopenia compared with individuals without this condition. Future research should clarify whether the specificity and number of medications is a direct contributor in accelerating the progression of muscle wasting and dysfunction contributing to sarcopenia in older adults.

Recent sarcopenia definitions-prevalence, agreement and mortality associations among men: Findings from population-based cohorts.

BACKGROUND: The 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. METHODS: White men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4-6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27 kg and ALM index <7.0 kg/m2 ), SDOC (grip strength <35.5 kg and gait speed <0.8 m/s) and Modified SDOC (grip strength <35.5 kg and gait speed <1.0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis. RESULTS: Mean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (κ = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I2 : 0.0%]; SDOC [2.75 (2.28, 3.31), I2 : 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I2 : 58.3%]. CONCLUSIONS: There was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

Lifestyle approaches to prevent and retard sarcopenia: A narrative review.

Sarcopenia, with its high prevalence and its adverse health outcomes, amongst older adults is considered a major public health problem. Its primary, secondary and tertiary preventions are therefore very important. Our objective was to review the effects of lifestyle factors, including not only dietary habits and exercise but also social use of substances such as alcohol and tobacco, on the incidence of sarcopenia and on its health outcomes. We found that the effect of lifestyle on muscle parameters or physical function has been investigated in many trials of heterogeneous design and quality. However, based on data from interventional studies, we can be confident that loss of physical function and its consequences can be counteracted by physical activity. There are some interesting data, mainly evident from observational studies, suggesting that healthier dietary patterns may improve muscle health. The combination of exercise with dietary supplement has more conflicting results and the effect of other lifestyle changes, such as cessation of alcohol or tobacco use, is difficult to establish clearly. Further high-quality trials are needed to substantiate the mechanism of action of each intervention as well as to determine the optimal modalities of these in older adults.

Neurofilament light chain concentration in an aging population.

BACKGROUND: Neurofilament light chain (NF-L) concentration is recognized to be modified in neurological diseases and traumatic brain injuries, but studies in the normal aging population are lacking. It is, therefore, urgent to identify influencing factors of NF-L concentration in the aging population. METHOD: We assessed NF-L concentration in sera of a large cohort of 409 community-dwelling adults aged over 65 years. We studied the association between NF-L and various physiological factors but also with self-reported comorbidities or life-style habits. RESULTS: We showed that NF-L concentration in serum was tightly associated with cystatin C concentration (r = 0.501, p < 0.0001) and consequently, to the estimated glomerular filtration rate (eGFR) (r = - 0.492; p < 0.0001). Additionally, NF-L concentration was dependent on age and body mass index (BMI) but not sex. Among the self-reported comorbidities, subjects who reported neurological disorders, cardiovascular diseases or history of fracture had higher NF-L concentration in univariate analysis, whereas it was only the case for subjects who reported neurological disorders in the multivariate analysis. NF-L concentration was also increased when Mini-Mental State Examination (MMSE) was decreased (≤ 25 points) but not when geriatric depression score (GDS) was increased (> 5 points) in both univariate and multivariate analysis. Finally, we are providing reference ranges by age categories for subjects with or without altered renal function. CONCLUSION: NF-L concentration in the aging population is not driven by the increasing number of comorbidities or depression. Yet, NF-L blood concentration is dependent on kidney function and NF-L interpretation in patients suffering from renal failure should be taken with caution.

A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes.

This study investigated the possible anti-inflammatory and chondroprotective effects of a combination of celecoxib and prescription-grade glucosamine sulfate (GS) in human osteoarthritic (OA) chondrocytes and their possible mechanism of action. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination with IL-1ß (10 ng/mL) and a specific nuclear factor (NF)-κB inhibitor (BAY-11-7082, 1 µM). Gene expression and release of some pro-inflammatory mediators, metalloproteinases (MMPs), and type II collagen (Col2a1) were evaluated by qRT-PCR and ELISA; apoptosis and mitochondrial superoxide anion production were assessed by cytometry; B-cell lymphoma (BCL)2, antioxidant enzymes, and p50 and p65 NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with IL-1ß significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1ß, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1ß. Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased BCL2; and limited p50 and p65. Celecoxib and GS combination demonstrated an increased inhibitory effect on IL-1ß than that observed by each single treatment. Drugs effects were potentiated by pre-incubation with BAY-11-7082. Our results demonstrated the synergistic effect of celecoxib and GS on OA chondrocyte metabolism, apoptosis, and oxidative stress through the modulation of the NF-κB pathway, supporting their combined use for the treatment of OA.

Assessment of the performance of the SarQoL® questionnaire in screening for sarcopenia in older people.

BACKGROUND: Because of its low prevalence and the need for physical tests to establish a diagnosis, recruiting sarcopenic people for clinical studies can be a resource-intensive process. AIMS: We investigated whether the SarQoL®, a 55-item questionnaire designed to measure quality of life in sarcopenia, could be used to identify older people with a high likelihood of being sarcopenic, and to compare its performance to the SARC-F tool. METHODS: We performed a secondary analysis of data from older, community-dwelling participants of the SarcoPhAge study, evaluated for sarcopenia according to the EWGSOP2 criteria, and who completed the SarQoL® and SARC-F questionnaires. We determined the optimal threshold to distinguish between sarcopenic and non-sarcopenic people with the Youden index. Screening performance was evaluated with the area under the curve (AUC) and by calculating sensitivity and specificity. RESULTS: The analysis of 309 participants provided an optimal threshold value of ≤ 52.4 points for identifying people with sarcopenia with the SarQoL® questionnaire, which resulted in a sensitivity of 64.7% (41.1-84.2%), a specificity of 80.5% (75.7-84.7%) and an AUC of 0.771 (0.652-0.889). Compared to the SARC-F, the SarQoL® has greater sensitivity (64.7% vs 52.39%), but slightly lower specificity (80.5% vs. 86.6%). DISCUSSION: The SarQoL® questionnaire showed acceptable screening accuracy, on par with the SARC-F. The optimal threshold of ≤ 52.4 points should be confirmed in other cohorts of older people. CONCLUSIONS: This exploratory study showed that the SarQoL® could potentially be applied in a screening strategy, with the added benefit of providing a measure of QoL at the same time.

Evaluating quality of life in frailty: applicability and clinimetric properties of the SarQoL® questionnaire.

BACKGROUND: The SarQoL® questionnaire was specifically designed to measure quality of life (QoL) in sarcopenia. Frailty and sarcopenia have areas of overlap, notably weak muscle strength and slow gait speed, which may mean that the SarQoL could provide a measure of QoL in frailty. This study aimed to evaluate the clinimetric properties of the SarQoL questionnaire in physical frailty using the Fried criteria. METHODS: Analyses were carried out on data from the Sarcopenia and Physical impairment with advancing Age study. Frailty was assessed with the Fried criteria and QoL with the SarQoL, the Short-Form 36-Item, and the EuroQoL 5-Dimension (EQ-5D) questionnaires. We evaluated discriminative power (with the Kruskal-Wallis analysis of variance test), internal consistency (with Cronbach's alpha), construct validity (through hypotheses testing), test-retest reliability (with the intraclass correlation coefficient), measurement error (calculating standard error of measurement and smallest detectable change), and responsiveness (through hypotheses testing and standardized response mean). RESULTS: In total, 382 participants were included for the validation and 117 for the responsiveness evaluation. They had a median age of 73 (69-79) years, took 5 (3-8) drugs, and had 4 (3-5) co-morbidities. There were more women (n = 223; 58.4%) than men and, in total, 172 (45%) robust, 167 (44%) pre-frail, and 43 (11%) frail participants. Discriminative power was confirmed when significantly lower (P < 0.001) overall SarQoL scores, and thus also worse QoL, were observed between robust [77.1 (64.35-85.90)], pre-frail [62.54 (53.33-69.57)], and frail [49.99 (40.45-56.06)] participants. Six of the SarQoL domains performed likewise, with significantly lower scores according to frailty status with Domain 7 (fears) being the exception. Internal consistency was good (α = 0.866). Convergent (using Short-Form 36-Item and EQ-5D) and divergent construct validity (using EQ-5D) was confirmed. Test-retest reliability was excellent [intraclass correlation coefficient = 0.918 (0.834-0.961)], with a standard error of measurement of 3.88 and a smallest detectable change of 10.76 points. We found moderate responsiveness when five of the nine hypotheses were confirmed, coupled with a large effect size for the overall SarQoL score (corrected standardized response mean of -1.44). CONCLUSIONS: The SarQoL questionnaire has adequate clinimetric properties for use with frail patients in clinical practice and trials and could provide data that are more appropriate and detailed than the generic questionnaires currently used.

Prediction of 5-year mortality risk by malnutrition according to the GLIM format using seven pragmatic approaches to define the criterion of loss of muscle mass.

OBJECTIVES: To assess the association between baseline malnutrition according to the GLIM format, using seven pragmatic approaches to define the criterion of loss of muscle mass, with mortality in the SarcoPhAge (Sarcopenia and Physical Impairment with advancing Age) study during a 5-year follow-up. Secondarily, to calculate diagnostic performance indicators, concordance, and feasibility of these 7 pragmatic approaches compared to the original GLIM criteria. METHODS: Post-hoc analysis of the SarcoPhAge cohort, which included 534 community-dwelling volunteers ≥65-year-old, followed-up from 2013 to 2019. Baseline malnutrition was defined by GLIM criteria and 7 approaches: 1) Omission of a reduced muscle mass as a criterion; 2) Substitution for handgrip strength, 3) Calf-circumference, 4) Mid-arm circumference, 5) Goodman's grid, 6) Ishii's score chart, and 7) Yu's formula. The association between malnutrition (according to GLIM criteria and the 7 approaches) and mortality was assessed by Cox-regressions. Sensitivity, Specificity, Positive (PPV), Negative (NPV) predictive values, area under the curve (AUC), Cohen-kappa coefficient, and TELOS-feasibility score were calculated. RESULTS: Data to calculate GLIM criteria were available for 373 subjects (73.07 ± 5.96 years, 56% women). Prevalence of malnutrition with GLIM criteria was 24.4% (ranged from 13.9% to 20.9% with the 7 approaches). GLIM criteria showed a HR = 3.38 (1.89-6.09) to predict mortality during the 5-year follow-up, which ranged from HR = 2.72 (1.51-4.91) to 3.94 (2.14-7.24) with the 7 approaches. All 7 approaches were feasible (TELOS ≥ 3), showed sensitivity ≥ 65%, specificity ≥ 95.4%, PPV ≥ 85%, NPV ≥ 88%, AUC ≥ 0.7 and had almost-perfect/strong concordance (k ≥ 0.7) with the original GLIM criteria. CONCLUSIONS: GLIM criteria and the 7 approaches predicted three-to four-fold mortality, all ensured an accurate diagnosis, and were feasible in clinical settings.

Mortality in malnourished older adults diagnosed by ESPEN and GLIM criteria in the SarcoPhAge study.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) criteria have been recently launched by consensus of the major nutrition societies. GLIM criteria are partly constructed on the previous definition of malnutrition developed by the European Society of Clinical Nutrition and Metabolism (ESPEN). We aimed to assess malnutrition according to the ESPEN and GLIM criteria at baseline and to determine the corresponding risk of mortality during a 4-year follow-up in community-dwelling older adults from the SarcoPhAge (Sarcopenia and Physical Impairment with advancing Age) study. The relationship between malnutrition and incidence of 4-year adverse health consequences (institutionalization, hospitalization, falls, and fractures) was assessed. METHODS: This prospective population-based cohort was part of SarcoPhAge, which included 534 older adults in Belgium, followed up from 2013 to 2019. Community-dwelling healthy volunteers ≥65 years old were recruited. Mortality and adverse health consequences were collected annually by interview or phone call. Baseline malnutrition was defined according to the GLIM and ESPEN criteria. Agreement between the two definitions was reported by Cohen's kappa coefficient. Adjusted Cox regression and Kaplan-Meier survival curves were performed for malnutrition. Logistic regression was used for the other outcomes. RESULTS: From 534 subjects in SarcoPhAge, the records for 411 participants (73.2 ± 6.05 years old; 55.7% women) had all the variables needed to apply the GLIM criteria. Prevalence of baseline malnutrition was 23.4% for GLIM and 7% for ESPEN criteria (k = 0.30, low agreement). The adjusted Cox regression showed a significant increased mortality risk according to malnutrition status as defined by the GLIM [adjusted hazard ratio = 4.41 (95% confidence interval: 2.17-8.97)] and ESPEN [adjusted hazard ratio = 2.76 (95% confidence interval: 1.16-6.58)] criteria. Survival curves differed significantly between malnourished and non-malnourished groups, regardless of the definition used (log rank P < 0.001 for both). No association was found between baseline malnutrition according to these two criteria and 4-year risk of institutionalization, hospitalization, falls, or fractures (all P > 0.05). CONCLUSIONS: Malnutrition according to the GLIM criteria was associated with a 4.4-fold higher mortality risk, double that of the ESPEN criteria, during a 4-year follow-up. No association was found between malnutrition according to these two criteria and incidence of other health adverse consequences. GLIM criteria anticipate mortality and might guide interventions, with important implications for clinical practice and research.

Cost-effectiveness of sequential treatment with abaloparatide followed by alendronate vs. alendronate monotherapy in women at increased risk of fracture: A US payer perspective.

OBJECTIVES: Emerging evidence supports sequential therapy with anabolic followed by antiresorptive in patients at high-risk of fragility fractures. This study assessed the cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) [(ABL/ALN)] compared to ALN monotherapy and to sequential treatment starting with antiresorptive therapy (ALN/ABL/ALN). METHODS: A previously validated Markov microsimulation model was used to estimate the cost-effectiveness of sequential ABL/ALN compared to ALN monotherapy and to sequential ALN/ABL/ALN from a lifetime US payer perspective. In line with practice guidelines, patients were assumed to receive ABL for 18 months followed by 5 years of ALN, or ALN monotherapy for 5 years, or a sequence of ALN for 2 years followed by 18 months of ABL and then by 3 years ALN. Evaluation was conducted for patients aged 50-80 years old with a BMD T-score ≤-3.5 and without a history of prior fracture, or with a T-score between -2.5 and -3.5 and a history of ≥ 1 osteoporotic fracture. RESULTS: Sequential ABL/ALN was cost-effective (threshold of US$150,000 per QALY) vs generic ALN monotherapy in women ≥60 years with a BMD T-score ≤-3.5 and in women with BMD T-score between -2.5 and -3.5 and history of osteoporotic fracture. In all simulated populations, sequential ABL/ALN therapy was dominant (lower costs, more QALYs) compared with sequential ALN/ABL/ALN, resulting from limited effect of ABL in patients previously treated with an antiresorptive agent. CONCLUSIONS: Sequential ABL/ALN therapy is cost-effective vs ALN monotherapy for US postmenopausal women aged ≥60 years at increased risk of fractures.

Total joint replacement improves pain, functional quality of life, and health utilities in patients with late-stage knee and hip osteoarthritis for up to 5 years.

OBJECTIVES: To study and identify the determinants of the impact on pain, function, and quality of life of a prosthetic replacement surgery after 5 years of survival in patients with osteoarthritis (OA) of the lower limb. METHOD: In total, 626 osteoarthritic patients from a University Hospital, divided in 2 groups (according to surgical site), were prospectively followed for 5 years after hip (n = 346) or knee (n = 280) replacement. Validated specific Western Ontario and McMaster Universities Arthritis Index (WOMAC) and generic (SF-36 and EQ) instruments assessing quality of life were used prior to surgery and yearly, thereafter. We defined a good outcome as a clinically relevant improvement in WOMAC greater than or equal to the minimally important difference (MID). Regressions showed the relationships among preoperative, perioperative, and postoperative measures and the evolution of WOMAC scores after 5 years (percent change). We also examined any predictors of good outcomes. RESULTS: The beneficial effect on quality of life observed during the first year after hip and knee arthroplasty (HA and KA) was maintained for up to 5 years. More than 3/4 of the patients in our study experienced a good outcome (86.04% in HA group and 79.91% in KA group). Both the good outcome and the 5-year change in WOMAC are predicted by preoperative (i.e., radiological severity, comorbidities, disability, and level of education), perioperative (i.e., length of hospital stay and place of discharge), and postoperative (i.e., complications) variables in the two groups. CONCLUSIONS: Joint arthroplasty is a highly valuable therapeutic strategy for hip or knee OA patients who do not respond to pharmacological management. These results represent a step towards the collection of robust, scientifically sound data that will facilitate the completion of health economic analyses in the field of OA. KEY POINTS: • This study reports the long term outcomes of hip and knee replacement surgery in late-stage OA.• We identified pre-, per-, and post-operative determinants which contribute to a greater improvement in pain and function, hence increasing patients' satisfaction.• These results could contribute to select an OA population which has a high probability to get an optimal benefit from total joint replacement.

Cost-effectiveness of sequential treatment with abaloparatide vs. teriparatide for United States women at increased risk of fracture.

OBJECTIVES: There is emerging evidence supporting sequential therapy with an osteoanabolic followed by an antiresorptive in patients at high-risk of fragility fractures. This study assessed the cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) [(ABL/ALN)] compared with teriparatide (TPTD) followed by ALN (TPTD/ALN). METHODS: A previously validated Markov microsimulation model was adapted to estimate the cost-effectiveness of sequential ABL/ALN compared with sequential TPTD/ALN and no treatment with a lifetime horizon from the US payer perspective. Patients were assumed to receive ABL or TPTD for 18 months followed by 5 years of ALN in line with clinical recommendations. The effects of ABL on fracture risk were derived from the ACTIVExtend trial. The effects of TPTD were assumed to be maintained during subsequent ALN treatment, consistent with ACTIVExtend findings for ABL. Evaluation was completed for patients, aged 50-80 years with a BMD T-score ≤ -3.5 or with a T-score between -2.5 and -3.5 and a history of ≥ one osteoporotic fracture. RESULTS: In all simulated populations, sequential ABL/ALN therapy was dominant (lower costs, higher QALYs) compared with sequential TPTD/ALN therapy, resulting from the improved efficacy and lower drug price of ABL. Probabilistic sensitivity analyses suggested that ABL/ALN was dominant in at least 99% of the simulations. Compared to no treatment, the cost per QALY gained of ABL/ALN was always below $130,000. CONCLUSIONS: Sequential ABL/ALN therapy is a cost-effective (dominant) strategy compared with sequential TPTD/ALN therapy for the treatment of US women at increased risk of fractures.

The health economics burden of sarcopenia: a systematic review.

Despite of better knowledge about sarcopenia, an optimal understanding of its consequences from a public health perspective remains a challenge. Specifically, the economic burden of the illness is unclear. As a support for the public health policy makers and other health actors, our objective was to perform a systematic review of the literature comparing healthcare costs between sarcopenic and non-sarcopenic patients (under the registration number CRD42018099291). A search for relevant articles was conducted on the Medline and Scopus databases. Rigorous eligibility criteria were established (e.g., subjects with sarcopenia, both men and women, mean age of the sarcopenic population) and applied by two investigators to identify suitable studies. The first screening phase, performed by 2 independent reviewers, covered 455 references. Fourteen relevant studies were included in the final analysis. Overall, we noted an important heterogeneity between studies in the way of assessing sarcopenia (i.e. operational definitions, tools and cut-offs used). There were also large variations between studies in their cost analysis settings (i.e., discrepancies in time horizon, types and sources of economic data). Most of the studies focused on hospitalization costs following surgery for a specific disease such as cancer. Finally, 11 out of the 14 studies reported higher healthcare costs for sarcopenic patients. However, most of the included studies have important methodological bias (e.g. potential confusion factors rarely taken into account), and low to moderate quality scores. More standardized research, taking into account all the limitations of the published studies, should be conducted to assess the true impact of sarcopenia on healthcare consumption.