Quality of life in sarcopenia measured with the SarQoL questionnaire: A meta-analysis of individual patient data.

Age-related sarcopenia, resulting from a gradual loss in skeletal muscle mass and strength, is pivotal to the increased prevalence of functional limitation among the older adult community. The purpose of this meta-analysis of individual patient data is to investigate the difference in health-related quality of life between sarcopenic individuals and those without the condition using the Sarcopenia Quality of Life (SarQoL) questionnaire. A protocol was published on PROSPERO. Multiple databases and the grey literature were searched until March 2023 for studies reporting quality of life assessed with the SarQoL for patients with and without sarcopenia. Two researchers conducted the systematic review independently. A two-stage meta-analysis was performed. First, crude (mean difference) and adjusted (beta coefficient) effect sizes were calculated within each database; then, a random effect meta-analysis was applied to pool them. Heterogeneity was measured using the Q-test and I2 value. Subgroup analyses were performed to investigate the source of potential heterogeneity. The strength of evidence of this association was assessed using GRADE. From the 413 studies identified, 32 were eventually included, of which 10 were unpublished data studies. Sarcopenic participants displayed significantly reduced health-related quality of life compared with non-sarcopenic individuals (mean difference = -12.32; 95 % CI = [-15.27; -9.37]). The model revealed significant heterogeneity. Subgroup analyses revealed a substantial impact of regions, clinical settings, and diagnostic criteria on the difference in health-related quality of life between sarcopenic and non-sarcopenic individuals. The level of evidence was moderate. This meta-analysis of individual patient data suggested that sarcopenia is associated with lower health-related quality of life measured with SarQoL.

Exposure to magnetic fields and childhood leukemia: a systematic review and meta-analysis of case-control and cohort studies.

The association between childhood leukemia and extremely low frequency magnetic fields (ELF-MF) generated by power lines and various electric appliances has been studied extensively during the past 40 years. However, the conditions under which ELF-MF represent a risk factor for leukemia are still unclear. Therefore, we have performed a systematic review and meta-analysis to clarify the relation between ELF-MF from several sources and childhood leukemia. We have systematically searched Medline, Scopus, Cochrane Database of Systematic Review and DARE to identify each article that has examined the relationship between ELF-MF and childhood leukemia. We have performed a global meta-analysis that takes into account the different measures used to assess magnetic field exposure: magnetic flux density measurements (<0.2 µT vs. >0.2 µT), distances between the child's home and power lines (>200 m vs. <200 m) and wire codings (low current configuration vs. high current configuration). Moreover, meta-analyses either based on magnetic flux densities, on proximity to power lines or on wire codings have been performed. The association between electric appliances and childhood leukemia has also been examined. Of the 863 references identified, 38 studies have been included in our systematic review. Our global meta-analysis indicated an association between childhood leukemia and ELF-MF (21 studies, pooled OR=1.26; 95% CI 1.06-1.49), an association mainly explained by the studies conducted before 2000 (earlier studies: pooled OR=1.51; 95% CI 1.26-1.80 vs. later studies: pooled OR=1.04; 95% CI 0.84-1.29). Our meta-analyses based only on magnetic field measurements indicated that the magnetic flux density threshold associated with childhood leukemia is higher than 0.4 µT (12 studies, >0.4 µT: pooled OR=1.37; 95% CI 1.05-1.80; acute lymphoblastic leukemia alone: seven studies, >0.4 µT: pooled OR=1.88; 95% CI 1.31-2.70). Lower magnetic fields were not associated with leukemia (12 studies, 0.1-0.2 µT: pooled OR=1.04; 95% CI 0.88-1.24; 0.2-0.4 µT: pooled OR=1.07; 95% CI 0.87-1.30). Our meta-analyses based only on distances (five studies) showed that the pooled ORs for living within 50 m and 200 m of power lines were 1.11 (95% CI 0.81-1.52) and 0.98 (95% CI 0.85-1.12), respectively. The pooled OR for living within 50 m of power lines and acute lymphoblastic leukemia analyzed separately was 1.44 (95% CI 0.72-2.88). Our meta-analyses based only on wire codings (five studies) indicated that the pooled OR for the very high current configuration (VHCC) was 1.23 (95% CI 0.72-2.10). Finally, the risk of childhood leukemia was increased after exposure to electric blankets (four studies, pooled OR=2.75; 95% CI 1.71-4.42) and, to a lesser extent, electric clocks (four studies, pooled OR=1.27; 95% CI 1.01-1.60). Our results suggest that ELF-MF higher than 0.4 µT can increase the risk of developing leukemia in children, probably acute lymphoblastic leukemia. Prolonged exposure to electric appliances that generate magnetic fields higher than 0.4 µT like electric blankets is associated with a greater risk of childhood leukemia.

Spanish translation, cultural adaptation and validation of the SarQoL®: a specific health-related quality of life questionnaire for sarcopenia.

BACKGROUND: In 2015, a specific health-related quality of life questionnaire for sarcopenia, SarQoL®, was developed and validated in French. Since then, SarQoL® has been adapted and validated in different languages. We prepared a translation, cultural adaptation and validation of the psychometric properties of the SarQoL® into Spanish. METHODS: A cross-sectional study with 86 participants. The translation and adaptation followed international guidelines with two direct translations, a synthesized version of the direct translations, two reverse translations, consensus by an expert committee of a pre-final version, pre-test by end users and final version. The discriminative power (logistic regression analyses), construct validity (Pearson and Spearman´s correlation), internal consistency (Cronbach´s alpha coefficient), test-retest reliability (intraclass correlation coefficient) and ceiling and floor effects were analyzed. RESULTS: The Spanish version showed good construct validity (high correlation with comparable domains of the SF-36), high internal consistency (Cronbach's alpha coefficient: 0.84) and excellent test-retest reliability (ICC: 0.967, 95%, CI 0.917 - 0.989). However, it had no discriminative power between sarcopenic and non-sarcopenic participants defined with the EWGSOP and FNIH diagnostic criteria of sarcopenia. It did show discriminative power between patients with decreased vs normal muscle strength (54.9 vs. 62.6, p 0.009) and low vs. normal physical performance (57.3 vs. 70.2; p 0.005). No ceiling or floor effect was found. CONCLUSIONS: The Spanish version of SarQoL® has similar psychometric properties to those of the original version of the instrument. It did not discriminate between sarcopenic and non-sarcopenic patients diagnosed according to the EWGSOP or FNIH criteria, but it did with those with low muscle strength and low physical performance.

Patients' preferences for quality-of-life aspects in sarcopenia: a best-worst scaling study.

PURPOSE: As information on patients' preferences regarding quality-of-life aspects in sarcopenia is lacking, this study aims to assess the relative importance of the 14 items of a QoL questionnaire designed for sarcopenia (the SF-SarQoL) using a best-worst scaling (BWS) survey. METHODS: Participants, aged 65 years or older and community dwelling, who previously participated in the SarcoPhAge study, received a BWS survey via the mail. An object case BWS was selected in which participants completed 12 choice tasks, picking the most and least important aspect from 4 out of 14 SF-SarQoL items for each task. Relative importance scores (RIS) were estimated using Hierarchical Bayes modelling. A cluster analysis was also conducted to investigate whether several profiles with regards to QoL preferences were present. RESULTS: A total of 163 participants were included, aged 75 (IQR: 73-81) years old, and mostly women (n = 107; 65.6%). Two items were found to be significantly more important than others: "feeling a reduction of physical capacity" (RIS = 11.26), and "having balance problems" (RIS = 11.09). The least important items were "experiencing difficulty carrying heavy objects" (RIS = 2.89), and "feeling a reduction in muscle mass" (RIS = 3.82). We found relatively weak evidence for the presence of two clusters. One cluster prioritized items related to falls where the second prioritized items related to feeling physically capable. CONCLUSION: Not all QoL aspects were equally important. The relative weight of each QoL aspect may be used to interpret QoL results obtained with the SF-SarQoL or to inform target outcomes in interventional studies.

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.

Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults.

BACKGROUND: In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. AIMS: The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. METHODS: This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. RESULTS: The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. CONCLUSION: The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Cross-sectional Evaluation of the Sarcopenia Quality of Life (SarQoL) Questionnaire: Translation and Validation of its Psychometric Properties.

BACKGROUND: The SarQoL, a quality-of-life questionnaire specific to sarcopenia, was developed in 2015 and has since been translated into a number of other languages. The main reason to introduce this new Ukrainian version of the questionnaire was to measure sarcopenic individuals' perceptions regarding their positions in life in the context of their culture and value systems. METHODS: The questionnaire was translated using a forward-backward approach with a pre-test. A total of 49 participants were recruited for the validation study. Sarcopenia was diagnosed according to the Ishii test. The validation analyses included discriminative power, internal consistency, floor and ceiling effects, construct validity, and test-retest reliability. We compared the SarQoL questionnaire to the Short-Form 36 and the EuroQoL-5 Dimensions. RESULTS: A total of 28 participants out of 49 were categorized as probably sarcopenic. They had a significantly lower quality of life (overall score 58.43±17.13 vs. 69.89±13.31; p=0.014). The internal consistency was excellent (α=0.898), with none of the domains showing a disproportionate influence on the homogeneity of the questionnaire. Convergent construct validity was also confirmed. The results indicated a near-perfect degree of test-retest reliability. CONCLUSIONS: The first Ukrainian version of the questionnaire is equivalent to the available original English version.

Equation models developed with bioelectric impedance analysis tools to assess muscle mass: A systematic review.

BACKGROUND & AIMS: This systematic review aims to systematically assess and summarize the equation models developed to estimate muscle mass with bioelectric impedance analysis (BIA) instruments against a reference instrument (DXA, MRI, CT-scan, Ultrasonography), in order to help researchers and clinicians choose the most adapted equation, depending on the device and the population in question. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was followed. Medline (via Ovid) and Scopus were searched in January 2019 for observational (transversal, longitudinal, retrospective) studies developing an equation prediction model to validate BIA against another reference method for the assessment of muscle mass. Study selection and data extraction was performed independently by two researchers. Methodological quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: 25 studies matched the inclusion criteria and were included in the present systematic review. Among them, 10 studies proposed an equation for subjects aged 65 years and older, 9 for adults, 4 for infants and 2 did not report the age of the population. A large heterogeneity was observed regarding the brand and type of BIA as well as the administration protocol (mode, frequency, number of electrodes, administration position and empty bladder/stomach or not). Most of the studies used DXA as the reference instrument, except 4 that used MRI. In each of the included papers authors provided, through simple or multiple regression, a predictive equation for muscle mass. BIA resistance index, sex, weight, age, BIA reactance and height were most frequently included as predictive variables. The majority of the equations developed explained more than 80% of the variance between both instruments. Out of the 25 equations available, only 9 were also validated in another population within the same paper. CONCLUSION: This systematic review of the literature offers clinicians and researchers the opportunity to verify the existence of a prediction equation when using a BIA device for estimating muscle mass. This will help them to obtain a valid estimation of muscle mass in a specific population and with a specific instrument. If the equation exists and has been validated by a study free of high risk of bias, it's use is recommended because the development of a new equation in the same context seems redundant and undesirable. If a validation has not been carried out for a specific brand of BIA, reference method or population, we recommend the development and cross-validation of a new equation.

Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS: GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.

Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

OBJECTIVE: We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. METHODS: A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue. RESULTS: The search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.29; I2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15-1.92; I2 = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96-3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73-1.27). CONCLUSIONS: Topical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.

Safety of Intra-articular Hyaluronic Acid Injections in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BACKGROUND: Some controversy exists regarding the safety of intra-articular hyaluronic acid (IAHA) in the management of osteoarthritis (OA). OBJECTIVE: The objective of this study was to re-assess the safety profile of IAHA in patients with OA, through a comprehensive meta-analysis of randomized, placebo-controlled trials. METHODS: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with IAHA in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, cardiac, vascular, respiratory, nervous system, skin and subcutaneous tissue disorders, musculoskeletal, renal and urinary disorders, infections and infestations, and hypersensitivity reaction. RESULTS: Database searches initially identified 1481 records. After exclusions according to the selection criteria, 22 studies were included in the qualitative synthesis, and nine studies having adequate data were ultimately included in the meta-analysis. From the studies excluded according to the pre-specified selection criteria, 21 with other pharmacological OA treatments permitted during the trials were a posteriori included in a parallel qualitative synthesis, from which eight studies with adequate data were finally included in a parallel meta-analysis. Since this meta-analysis was designed to assess safety, the exclusion criterion on concomitant anti-OA medication was crucial. However, due to the high number of studies that allowed mainly concomitant oral non-steroidal anti-inflammatory drugs (NSAIDs), we decided to include them in a post hoc parallel analysis in order to compare the results from the two analyses. No statistically significant difference in odds was found between IAHA and placebo for all types of SOC-related disorders, except for infections and infestations, for which significantly lower odds were found with IAHA compared with placebo, both overall (odds ratio [OR] = 0.61, 95% confidence interval [CI] 0.40-0.93; I2 = 0%) and in studies without concomitant anti-OA medication (OR = 0.49, 95% CI 0.27-0.89). There were significant increased odds of reporting serious AEs with IAHA compared with placebo, both overall (OR = 1.78, 95% CI 1.21-2.63; I2 = 0%) and in studies with concomitant anti-OA medication (OR = 1.78, 95% CI 1.10-2.89), but not in studies without concomitant anti-OA medication (OR = 1.78, 95% CI 0.92-3.47). CONCLUSIONS: Using the available data on studies without any concomitant anti-OA medication permitted during clinical trials, IAHA seems not to be associated with any safety issue in the management of OA. However, this evidence was associated with only a "low" to "moderate" certainty. A possible association with increased risk of serious AEs, particularly when used with concomitant OA medications, requires further investigation.

Standard error of measurement and smallest detectable change of the Sarcopenia Quality of Life (SarQoL) questionnaire: An analysis of subjects from 9 validation studies.

OBJECTIVES: The Sarcopenia Quality of Life (SarQoL) questionnaire, a sarcopenia-specific patient-reported outcome measure, evaluates quality of life with 55 items. It produces 7 domain scores and 1 overall quality of life score, all between 0 and 100 points. This study aims to contribute to the interpretation of the SarQoL scores by calculating the standard error of measurement (SEM) and smallest detectable change (SDC) in a sample of subjects from 9 studies. METHODS: Subjects from 9 studies (conducted in Belgium, Brazil, Czech Republic, England, Greece, Lithuania, Poland and Spain) were included. The SEM, a measure of the error in the scores that is not due to true changes, was calculated by dividing the standard deviation of the difference between test and retest scores (SDdiff) by √2. The SDC, defined as change beyond measurement error, was calculated by multiplying SDdiff by 1.96. Bland-Altman plots were assessed for the presence of systematic errors. RESULTS: A total of 278 sarcopenic subjects, aged 77.67 ± 7.64 years and 61.5% women, were included. The SEM for the overall SarQoL score ranged from 0.18 to 4.20 points for the individual studies, and was 2.65 points when all subjects were analyzed together. The SDC for the overall score ranged from 0.49 to 11.65 points for the individual studies, and was 7.35 points for all subjects. The Bland-Altman plots revealed no systematic errors in the questionnaire. CONCLUSION: This study shows that, for individual subjects, a change in overall quality of life of at least 7.35 points (on a scale from 0 to 100) would have to be observed to confirm that a true change, beyond measurement error, has occurred. It also demonstrated that the SarQoL questionnaire is a precise instrument, with the observed scores within less than 3 points of the theoretical "true score".

Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials.

INTRODUCTION: There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. METHODS: We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. RESULTS: The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I2 = 94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: - 0.25; 95% CI: - 0.34, - 0.16; I2 = 75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: - 0.08; 95% CI: - 0.19, + 0.02; I2 = 20%; SMDFunction: - 0.18; 95% CI: - 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses. CONCLUSION: This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.

Validation of the Lithuanian version of sarcopenia-specific quality of life questionnaire (SarQoL®).

PURPOSE: The aim of this study was to translate and culturally adapt the SarQoL® questionnaire into Lithuanian and investigate its main psychometric properties. METHODS: A cross-sectional study was performed on community-dwelling Lithuanian people aged ≥ 60 years. The revised criteria of the European Working Group on Sarcopenia in Older People were used. A forward-backward methodology was used for the translation, with a pre-test of the final version of the Lithuanian SarQoL® questionnaire. Adjusted logistic regression analysis was used to compare sarcopenic and non-sarcopenic subjects. Internal consistency was determined using Cronbach's alpha coefficient. The correlation of total score of the SarQoL® and each domain of the Short-form General Health Survey (SF-36) and EuroQol-5D (EQ-5D) questionnaires was measured using Spearman's correlations. Test-retest reliability was measured by the intraclass correlation coefficient. RESULTS: The study was performed on 176 subjects. Fifty-eight subjects were diagnosed with sarcopenia. After adjustment for confounders, the total score of the SarQoL® questionnaire was significantly lower for sarcopenic subjects compared to non-sarcopenic subjects (50.32 ± 8.58 vs 73.75 ± 13.51, p < 0.001). Cronbach's alpha coefficient was 0.95. Neither floor nor ceiling effects were found. The SarQoL® questionnaire revealed good correlation with similar domains of the SF-36 and EQ-5D questionnaires for convergent validity and weak correlations with different domains for divergent validity, confirming its construct validity. An excellent agreement between test and retest was found with an ICC of 0.976 (95% CI 0.959-0.986). CONCLUSIONS: Lithuanian version of the SarQoL® is valid, reliable and consistent and could be used to assess quality of life in sarcopenic population.

Translation and validation of the Dutch SarQoL®, a quality of life questionnaire specific to sarcopenia.

OBJECTIVES: To translate the Sarcopenia Quality of Life (SarQoL®) questionnaire into Dutch and to evaluate the psychometric properties of the Dutch version of this questionnaire. METHODS: The translation was carried out using a 5-step process, with 2 initial translations, a merging of these 2 translations, 2 backwards translations, an expert committee review and a pretest of the questionnaire. Sarcopenia was diagnosed with the EWGSOP algorithm. The validation consisted of an examination of the discriminative power, internal consistency, construct validity, test-retest reliability and floor and ceiling effects. RESULTS: No significant problems were encountered during the translation process. A total of 92 subjects were included in the validation part of this study, 30 of which were sarcopenic. Discriminative power between sarcopenic and non-sarcopenic subjects was found for all domains and the Overall score (median overall QoL score: 67.15 vs 79.72; p=0.003). High internal consistency was found (Cronbach's alpha=0.883), as well as good construct validity with 75% of hypotheses confirmed. Test-retest reliability was excellent (ICC=0.976; 95% CI=0.947-0.989) and no floor or ceiling effects were observed. CONCLUSION: The Dutch version of the SarQoL® questionnaire is ready for use in clinical and research applications.

Evaluation of the Responsiveness of the SarQoL® Questionnaire, a Patient-Reported Outcome Measure Specific to Sarcopenia.

INTRODUCTION: The Sarcopenia Quality of Life (SarQoL®) questionnaire was developed to provide a patient-reported outcome measure specific to sarcopenia. Its psychometric properties indicate that it is a valid and reliable instrument. However, until now, its ability to detect change over time has not been examined. Therefore, the objective of this study is to evaluate the responsiveness (also known as sensitivity to change) of the SarQoL® questionnaire in a prospective, longitudinal cohort of community-dwelling, older, sarcopenic subjects. METHODS: Sarcopenic subjects from the SarcoPhAge (Sarcopenia and Physical impairment with advancing Age) study were included. Responsiveness was evaluated with nine pre-specified hypotheses on the correlation between the evolution of the SarQoL® scores after a 2-year interval and the evolution of the scores on the Short Form-36 (SF-36) and the Euroqol 5-dimension (EQ-5D) questionnaires. This technique considers responsiveness to be a form of longitudinal validity. Additionally, standardized response means were also calculated to compare the quantity of change measured by the different questionnaires. RESULTS: A total of 42 sarcopenic subjects were included. The median age of the sample was 72.9 (68.9-78.8) years, 59.5% were female, and the mean body mass index was 23.3 (20.4-25.7) kg/m2. A good responsiveness was observed, as evidenced by the confirmation of eight out of nine hypotheses, well above the 75% confirmation threshold. The standardized response mean of the Overall SarQoL® score was significantly higher than those of the SF-36 Physical Component Summary (p = 0.005), the EQ-5D Utility Index (p < 0.001) and the Euroqol visual analogue scale (p = 0.003). CONCLUSION: The first data available on the ability of the SarQoL® questionnaire to detect change over time indicates that the questionnaire has good responsiveness. This, together with the previously established psychometric properties, confirms that the SarQoL® questionnaire is a relevant instrument for the assessment of quality of life in sarcopenic populations.

Current review of the SarQoL®: a health-related quality of life questionnaire specific to sarcopenia.

INTRODUCTION: Sarcopenia, defined by a progressive and generalized loss of muscle mass and muscle function, is associated with many harmful clinical consequences. Several studies have reported the impact of sarcopenia on health-related quality of life (HRQoL) using generic quality of life (QoL) questionnaires. The results of these observational studies are quite heterogenous. Indeed, generic tools may not be able to detect subtle effects of sarcopenia on QoL. Recently, a sarcopenia-specific HRQoL questionnaire was developed and validated in a population of sarcopenic subjects to more accurately assess the impact of sarcopenia on QoL. Areas covered: The purpose of this review is to present evidence regarding the impact of sarcopenia on QoL and to introduce a new specific HRQoL questionnaire, the SarQoL®. Expert commentary: The self-administered SarQoL®, initially developed in French, comprises 55 items translated into 22 questions. The questionnaire has been shown to be understandable, valid, consistent, and reliable and can therefore be recommended for clinical and research purposes. The questionnaire is now available in 11 different languages with another 20 translations in progress. The instrument's sensitivity to change still needs to be assessed in future longitudinal studies.