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.

Early Coronary Artery Calcification Progression over Two Years in Breast Cancer Patients Treated with Radiation Therapy: Association with Cardiac Exposure (BACCARAT Study).

Background: Radiotherapy (RT) for breast cancer (BC) can induce coronary artery disease many years after RT. At an earlier stage, during the first two years after RT, we aimed to evaluate the occurrence of increased coronary artery calcium (CAC) and its association with cardiac exposure. Methods: This prospective study included 101 BC patients treated with RT without chemotherapy. Based on CAC CT scans performed before and two years after RT, the event 'CAC progression' was defined by an increase in overall CAC score (CAC RT+ two years­CAC before RT > 0). Dosimetry was evaluated for whole heart, left ventricle (LV), and coronary arteries. Multivariable logistic regression models were used to assess association with doses. Results: Two years after RT, 28 patients presented the event 'CAC progression', explained in 93% of cases by a higher CAC score in the left anterior descending coronary (LAD). A dose−response relationship was observed with LV exposure (for Dmean LV: OR = 1.15, p = 0.04). LAD exposure marginally explained increased CAC in the LAD (for D2 LV: OR =1.03, p = 0.07). Conclusion: The risk of early CAC progression may be associated with LV exposure. This progression might primarily be a consequence of CAC increase in the LAD and its exposure.

Association Between Cardiac Radiation Exposure and the Risk of Arrhythmia in Breast Cancer Patients Treated With Radiotherapy: A Case-Control Study.

Background: Previous studies suggested that radiation therapy (RT) for breast cancer (BC) can induce cardiac arrhythmias and conduction disorders. However, the association with mean heart dose and specific cardiac substructures doses was less studied. Materials and Methods: We conducted a nested case-control study based on French BC patients, enrolled in the European MEDIRAD-BRACE study (https://clinicaltrials.gov, Identifier: NCT03211442), who underwent three-dimensional conformal radiation therapy (3D-CRT) between 2009 and 2013 and were retrospectively followed until 2019. Cases were incident cases of cardiac arrhythmia. Controls without arrhythmia were selected with propensity-scored matching by age, duration of follow-up, chemotherapy, hypertension, and diabetes (ratio 1:4 or 5). Doses to the whole heart (WH), left and right atria (LA and RA), and left and right ventricles (LV and RV) were obtained after delineation with multi-atlas-based automatic segmentation. Results: The study included 116 patients (21 cases and 95 controls). Mean age at RT was 64 ± 10 years, mean follow-up was 7.0 ± 1.3 years, and mean interval from RT to arrhythmia was 4.3 ± 2.1 years. None of the results on association between arrhythmia and cardiac doses reached statistical significance. However, the proportion of right-sided BC was higher among patients with arrhythmia than among controls (57% vs. 51%, OR = 1.18, p = 0.73). Neither mean WH dose, nor LV, RV, and LA doses were associated with an increased risk of arrhythmia (OR = 1.00, p > 0.90). In contrast, the RA dose was slightly higher for cases compared to controls [interquartile range (0.61-1.46 Gy) vs. (0.49-1.31 Gy), p = 0.44], and a non-significant trend toward a potentially higher risk of arrhythmia with increasing RA dose was observed (OR = 1.19, p = 0.60). Subanalysis according to BC laterality showed that the association with RA dose was reinforced specifically for left-sided BC (OR = 1.76, p = 0.75), while for right-sided BC, the ratio of mean RA/WH doses may better predict arrhythmia (OR = 2.39, p = 0.35). Conclusion: Despite non-significant results, our exploratory investigation on BC patients treated with RT is the first study to suggest that right-sided BC patients and the right atrium irradiation may require special attention regarding the risk of cardiac arrhythmia and conduction disorders. Further studies are needed to expand on this topic.

Subclinical Left Ventricular Dysfunction Detected by Speckle-Tracking Echocardiography in Breast Cancer Patients Treated With Radiation Therapy: A Six-Month Follow-Up Analysis (MEDIRAD EARLY-HEART study).

Background: In the case of breast cancer (BC), radiotherapy (RT) helps reduce locoregional recurrence and BC-related deaths but can lead to cardiotoxicity, resulting in an increased risk of long-term major cardiovascular events. It is therefore of primary importance to early detect subclinical left ventricular (LV) dysfunction in BC patients after RT and to determine the dose-response relationships between cardiac doses and these events. Methods: Within the frame of the MEDIRAD European project (2017-2022), the prospective multicenter EARLY-HEART study (ClinicalTrials.gov Identifier: NCT03297346) included chemotherapy naïve BC women aged 40-75 years and treated with lumpectomy and adjuvant RT. Myocardial strain analysis was provided using speckle-tracking echocardiography performed at baseline and 6 months following RT. A global longitudinal strain (GLS) reduction >15% between baseline and follow-up was defined as a GLS-based subclinical LV dysfunction. Individual patient dose distributions were obtained using multi-atlas-based auto-segmentation of the heart. Dose-volume parameters were studied for the whole heart (WH) and left ventricle (LV). Results: The sample included 186 BC women (57.5 ± 7.9 years, 64% left-sided BC). GLS-based subclinical LV dysfunction was observed in 22 patients (14.4%). These patients had significantly higher cardiac exposure regarding WH and LV doses compared to patients without LV dysfunction (for mean WH dose: 2.66 ± 1.75 Gy versus 1.64 ± 0.96 Gy, p = 0.01). A significantly increased risk of subclinical LV dysfunction was observed with the increase in the dose received to the WH [ORs from 1.13 (V5) to 1.74 (Dmean); p <0.01] and to the LV [ORs from 1.10 (V5) to 1.46 (Dmean); p <0.01]. Based on ROC analysis, the LV-V5 parameter may be the best predictor of the short-term onset of subclinical LV dysfunction. Conclusion: These results highlighted that all cardiac doses were strongly associated with the occurrence of subclinical LV dysfunction arising 6 months after BC RT. Whether measurements of GLS at baseline and 6 months after RT combined with cardiac doses can early predict efficiently subclinical events occurring 24 months after RT remains to be investigated.

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.

Transmission of SARS-CoV-2 After COVID-19 Screening and Mitigation Measures for Primary School Children Attending School in Liège, Belgium.

Importance: Recent data suggest a relatively low incidence of COVID-19 among children. The possible role that children attending primary school may play in the transmission of SARS-CoV-2 remains poorly understood. Objective: To gain a better understanding of the possible role of children in the transmission of SARS-CoV-2. Design, Setting, and Participants: This prospective cohort study was conducted from September 21 to December 31, 2020, in a primary school in Liège, Belgium, among a volunteer sample of 181 children, parents, and school employees. Exposures: Participants were tested for SARS-CoV-2 infection once a week for 15 weeks through throat washing, performed with 5 mL of saline and collected in a sterile tube after approximately 30 seconds of gargling. Quantitative reverse transcription-polymerase chain reaction was performed to detect SARS-CoV-2 infection. Main Outcomes and Measures: In case of test positivity, participants were asked to complete a questionnaire aimed at determining the timing of symptom onset and symptom duration. SARS-CoV-2 genetic sequencing was also performed. Confirmed cases were linked based on available information on known contacts and viral sequences. Results: A total of 181 individuals participated in this study, including 63 children (34 girls [54.0%]; mean [SD] age, 8.6 [1.9] years [range, 5-13 years]) and 118 adults (75 women [63.6%]; mean [SD] age, 42.5 [5.7] years [range, 30-59 years]). Forty-five individuals (24.9%) tested positive: 13 children (20.6%; 95% CI, 10.6%-30.6%) and 32 adults (27.1%; 95% CI, 19.1%-35.7%) (P = .34). Children were more often asymptomatic compared with adults (6 [46.2%; 95% CI, 19.1%-73.3%] vs 4 of 31 [12.9%; 95% CI, 1.3%-24.5%]; P = .04). The median duration of symptoms was shorter in children than in adults (0.00 days [IQR, 0.00-1.00 days] vs 15.00 days [IQR, 7.00-22.00 days]). A reconstruction of the outbreak revealed that most transmission events occurred between teachers and between children within the school. Of the observed household transmission events, most seemed to have originated from a child or teacher who acquired the infection at school. Conclusions and Relevance: Despite the implementation of several mitigation measures, the incidence of COVID-19 among children attending primary school in this study was comparable to that observed among teachers and parents. Transmission tree reconstruction suggests that most transmission events originated from within the school. Additional measures should be considered to reduce the transmission of SARS-CoV-2 at school, including intensified testing.

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.

The "Ankle Instability Instrument": Cross-cultural adaptation and validation in French.

BACKGROUND: Functional ankle instability affects 20-40% of individuals who have already suffered from a sprain. Such dysfunctions are difficult to diagnose. Therefore, the information provided by self-administered questionnaires is essential. Thus, the Ankle Instability Instrument (AII) was developed and initially validated in English. Our goal is to create a French version of the instrument, named AII-F, by scrupulously respecting the cultural adaptation phases and to make sure the new instrument has good psychometric properties. METHODS: International recommendations have been rigorously followed for the cultural adaptation and the French-translation phase. Six steps are recommended: I) two initial translations from English to French; II) synthesis of the two versions; III) back-translations from French to English; IV) comparisons between the back-translations and the original questionnaire by the expert committee; V) pretest; and VI) approval of the final French version of the AII. In order to validate this French-translation, 91 subjects suffering from ankle instability matched to 91 healthy subjects were asked to complete the AII-F. The Short Form Health Survey (SF-36) was used as a comparative questionnaire as well as the French Cumberland Ankle Instability Tool (CAIT-F). The psychometric properties of the questionnaire were evaluated by determining the test-retest reliability after a 10-14-day interval, the internal consistency, construct validity, and the floor/ceiling effects. RESULTS: The French-translation did not pose a problem and could be validated by the expert committee. The AII-F showed a very good test-retest reliability for the total score, with an Intra Class Coefficient of 0.983. The internal coherence is high with an alpha coefficient of Cronbach of 0.861. The association of the AII-F with the CAIT-F was high, for the summary of the physical component of the SF-36, meaning a great convergent validity. The other subscales of the SF-36 (mental health) were weakly correlated with the AII-F, reflecting good divergent validity. An optimal cut-off score was obtained to dissociate pathological patients from healthy subjects: when the subject responded to "yes" 5 times or more, he is considered, with a very high degree of confidence, to be pathological. CONCLUSION: The AII-F is reliable and valid for evaluating and measuring functional ankle instability.

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.

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.