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Obesity is a global pandemic, but there is yet no effective measure to control it. Recent metabolomics studies have identified a signature of altered amino acid profiles to be associated with obesity, but it is unclear whether these findings have actionable clinical potential. The aims of this study were to reveal the metabolic alterations of obesity and to explore potential strategies to mitigate obesity. We performed targeted metabolomic profiling of the plasma/serum samples collected from six independent cohorts and conducted an individual data meta-analysis of metabolomics for body mass index (BMI) and obesity. Based on the findings, we hypothesized that restriction of branched-chain amino acids (BCAAs), phenylalanine, or tryptophan may prevent obesity and tested our hypothesis in a dietary restriction trial with eight groups of 4-week-old male C57BL/6J mice (n = 5/group) on eight different types of diets, respectively, for 16 weeks. A total of 3397 individuals were included in the meta-analysis. The mean BMI was 30.7 ± 6.1 kg/m2, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all p ≤ 2.58 × 10-4), linked to alterations of the BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways. The restriction of BCAAs within a high-fat diet (HFD) maintained the mice's weight, fat and lean volume, subcutaneous and visceral adipose tissue weight, and serum glucose and insulin at levels similar to those in the standard chow group, and prevented obesity, adipocyte hypertrophy, adipose inflammation, and insulin resistance induced by HFD. Our data suggest that four metabolic pathways, BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways, are altered in obesity and restriction of BCAAs within a HFD can prevent the development of obesity and insulin resistance in mice, providing a promising strategy to potentially mitigate diet-induced obesity.

Background: The characterization and influence of preoperative health care use on quality-of-care indicators (e.g., readmissions) has received limited attention in populations with musculoskeletal disorders. The purpose of this study was to characterize preoperative health care use and examine its effect on quality-of-care indicators among patients undergoing elective surgery for osteoarthritis. Methods: Data on health care use for 124,750 patients with elective surgery for osteoarthritis in Ontario, Canada, from April 1, 2015 to March 31, 2018 were linked across health administrative databases. Using total health care use one-year previous to surgery, patients were grouped from low to very high users. We used Poisson regression models to estimate rate ratios, while examining the relationship between preoperative health care use and quality-of-care indicators (e.g., extended length of stay, complications, and 90-day hospital readmissions). We controlled for covariates (age, sex, neighborhood income, rural/urban residence, comorbidities, and surgical anatomical site). Results: We found a statistically significant trend of increasing worse outcomes by health care use gradients that persisted after controlling for patient demographics and comorbidities. Findings were consistent across surgical anatomical sites. Moreover, very high users have relatively large numbers of visits to non-musculoskeletal specialists. Conclusions: Our findings highlight that information on patients' preoperative health care use, together with other risk factors (such as comorbidities), could help decision-making when benchmarking or reimbursing hospitals caring for complex patients undergoing surgery for osteoarthritis. [ABSTRACT FROM AUTHOR]

Objectives Knee pain is the major driver for OA patients to seek healthcare, but after pursuing both conservative and surgical pain interventions, ∼20% of patients continue to report long-term pain following total knee arthroplasty (TKA). This study aimed to identify a metabolomic signature for sustained knee pain after TKA to elucidate possible underlying mechanisms. Methods Two independent cohorts from St John's, NL, Canada (n  = 430), and Toronto, ON, Canada (n  = 495) were included in the study. Sustained knee pain was assessed using the WOMAC pain subscale (five questions) at least 1 year after TKA for primary OA. Those reporting any pain on all five questions were considered to have sustained knee pain. Metabolomic profiling was performed on fasted pre-operative plasma samples using the Biocrates Absolute IDQ p180 kit. Associations between metabolites and pair-wise metabolite ratios with sustained knee pain in each individual cohort were assessed using logistic regression with adjustment for age, sex and BMI. Random-effects meta-analysis using inverse variance as weights was performed on summary statistics from both cohorts. Results One metabolite, phosphatidylcholine (PC) diacyl (aa) C28:1 (odds ratio = 0.66, P  = 0.00026), and three metabolite ratios, PC aa C32:0 to PC aa C28:1, PC aa C28:1 to PC aa C32:0, and tetradecadienylcarnitine (C14:2) to sphingomyelin C20:2 (odds ratios = 1.59, 0.60 and 1.59, respectively; all P  < 2 × 10−5), were significantly associated with sustained knee pain. Conclusions Though further investigations are needed, our results provide potential predictive biomarkers and drug targets that could serve as a marker for poor response and be modified pre-operatively to improve knee pain and surgical response to TKA. [ABSTRACT FROM AUTHOR]

Background: A relation between provider volume and outcome of total joint replacement (TJR) has not been demonstrated in Canada. Given the recent increase in TJR, changing patient characteristics and small sizes of previous Ontario studies, we reassessed whether adverse outcomes of TJR are related to hospital and surgeon procedure volumes. Methods: We included all Ontarians aged 20 years and older who underwent a unilateral elective primary total hip replacement (THR) or total knee replacement (TKR) between April 2000 and March 2004. The main data sources were hospital discharge abstracts and physician billings. We defined provider volume as the average annual number of primary and revision procedures performed by hospitals and surgeons during the study period. We assessed the association between procedure volumes and acute length of hospital stay (ALOS) and between volume and rate of surgical complications during the index admission; death within 90 days of operation; readmission for amputation, fusion or excision within 1 year; and revision arthroplasty within 1 year. We adjusted for age, sex, comorbidity, arthritis type, teaching hospital status and discharge disposition. The analyses of hospital volume were adjusted for surgeon volume and vice versa. Results: We included 20 290 patients who received THR and 27 217 who received TKR. Patient age, sex and comorbidity were significant predictors of complications and mortality. There were no associations between provider volume and mortality. Findings for other outcomes were mixed. Surgeon procedure volume was related to rates of revision THR but not to rates of revision TKR. Shorter ALOS was associated with male sex, younger age, fewer comorbidities, discharge to a rehabilitation unit or facility and greater surgeon volume. Conclusion: Patient characteristics were significant predictors of complications, ALOS and mortality after primary TJR. Evidence for a relation between provider volume and outcome was limited and inconsistent. Contexte : On n&apos;a pas demontre de lien, au Canada, entre le volume des interventions pratiquees et les resultats de l&apos;arthroplastie totale. Etant donne l&apos;augmentation recente du nombre d&apos;arthroplasties totales, l&apos;evolution des caracteristiques des patients et l&apos;envergure limitee des etudes realisees auparavant en Ontario, nous avons voulu reevaluer la situation pour voir s&apos;il existe un lien entre les resultats indesirables de l&apos;arthroplastie totale et le volume des interventions pratiquees par les hopitaux et les chirurgiens. Methodes : Nous avons inclus tous les Ontariens de 20 ans et plus qui ont subi une arthroplastie totale de la hanche (ATH) ou du genou (ATG) primaire elective unilaterale entre avril 2000 et mars 2004. Les resumes de conge de l&apos;hopital et les factures des medecins ont constitue les principales sources de donnees. Nous avons defini le volume des interventions pratiquees par le fournisseur comme etant le nombre annuel moyen d&apos;interventions primaires et de revisions pratiquees par les hopitaux et les chirurgiens au cours de la periode a l&apos;etude. Nous avons analyse le lien entre les volu mes d&apos;interventions et la duree de l&apos;hospitalisation en milieu de soins actifs (DMS) et entre le volume et le taux de complications chirurgicales au cours de l&apos;admission temoin, les deces dans les 90 jours de l&apos;intervention, la readmission pour une amputation, une fusion ou une excision dans l&apos;annee, et l&apos;arthroplastie de revision dans l&apos;annee. Nous avons tenu compte de l&apos;age, du sexe, de la presence d&apos;une comorbidite, du type d&apos;arthrite, du statut d&apos;hopital d&apos;enseignement et du resultat au conge. Les analyses du volume des interventions pratiquees a l&apos;hopital ont ete rajustees en fonction du volume des interventions pratiquees par le chirurgien et vice versa. Resultats : Nous avons inclus 20 290 patients qui ont subi une ATH et 27 217 qui ont subi une ATG. L&apos;age et le sexe du patient et la presence d&apos;une comorbidite constituaient des predicteurs importants de complications et de mortalite. Il n&apos;y avait aucun lien entre le volume des interventions pratiquees par le fournisseur et la mortalite Les constatations dans le cas d&apos;autres resultats ont ete mixtes. On a etabli un lien entre le volume des interventions pratiquees par le chirurgien et les taux d&apos;ATH de revision, mais non les taux d&apos;ATG de revision. On a etabli un lien entre une DMS plus courte et le sexe masculin, l&apos;age plus jeune, la presence de comorbidites moins nombreuses, le transfert a un service ou un etablissement de readaptation et le volume plus eleve d&apos;interventions pratiquees par le chirurgien. Conclusion : Les caracteristiques des patients constituaient d&apos;importants predicteurs de complications, de DMS et de mortalite apres une arthroplastie totale primaire. Les preuves d&apos;un lien entre le volume des interventions pratiquees par le fournisseur et le resultat ont ete limitees et erratiques., Total joint replacements (TJRs) are among the most frequently performed surgical procedures in the world, and the number performed annually has increased steadily over the last decade. Between 1995 and [...]

Background: The best measure of body habitus as a risk factor for chronic disease is not well defined. Our intent was to examine the relation between waist-hip ratio (WHR) and body mass index (BMI) as a measurement of body habitus in patients with end-stage knee osteoarthritis (OA). Methods: We reviewed the data of 200 consecutive patients in our registry undergoing knee replacement surgery for demographic data of age, sex, BMI and WHR. We performed a stratified analysis by sex and calculated the risk ratios (RRs) to describe the risk of being classified as obese by WHR for those considered obese by the BMI criteria. Results: A similar percentage of male and female patients were classified as obese by the BMI criteria (38% v. 42%, respectively). Men were classified as obese more often than women by WHR (92% v. 82%). The RR of being obese as determined by WHR if classified as obese by the BMI criteria was 1.04 (95% confidence interval [CI] 0.91-1.18) for men and 1.23 (95% CI 1.03-1.46) for women. Conclusion: Among patients with knee OA, the overlap between BMI and WHR is greater in women than men. This difference has implications for defining the prevalence of metabolic syndrome in this population. Contexte: La meilleure mesure du phenotype corporel comme facteur de risque de maladie chronique n'est pas bien definie. Nous voulions etudier le lien entre le rapport taille-hanches (RTH) et l'indice de masse corporelle (IMC) comme mesure du phenotype corporel chez les patients qui ont une arthrose du genou (AG) au stade ultime. Methodes: Nous avons etudie les dossiers de 200 patients consecutifs inscrits dans notre registre qui ont subi une arthroplastie du genou pour degager des donnees demographiques sur l'age, le sexe, l'IMC et le RTH. Nous avons effectue une analyse stratifiee selon le sexe et calcule le risque relatif (RR) afin de decrire le risque d'etre classifie comme obese en fonction du RTH chez les personnes considerees comme obeses selon les criteres de l'IMC. Resultats: Un pourcentage semblable de patients des deux sexes ont ete classifies comme obeses en fonction des criteres de l'IMC (38 % c. 42 %, respectivement). Les hommes ont ete classes obeses plus souvent que les femmes selon le RTH (92 % c. 82 %). Le RR d'etre obese selon le RTH des personnes classees comme obeses selon les criteres de l'IMC s'est etabli a 1,04 (intervalle de confiance [IC] a 95 %, 0,91-1,18) chez les hommes et a 1,23 (IC a 95 %, 1,03-1,46) chez les femmes. Conclusion: Chez les patients atteints d'arthrose du genou, le chevauchement entre l'IMC et le RTH est plus important chez les femmes que chez les hommes. Cette difference a des repercussions sur la definition de la prevalence du syndrome metabolique dans cette population., Metabolic syndrome (MetS) is cluster of the following comorbidities: obesity, elevated fasting glucose, high blood pressure and dyslipidemia. (1,2) Patients with MetS have a systemic proinflammatory and prothrombotic state, which [...]

Background: Studies have shown that women present for surgery at an older age and with greater dysfunction than do men; however, the explanation for this finding is unclear. We investigated the impact living status (alone or with another person) and sex the on timing and outcomes of hip and knee replacement surgery. Methods: We surveyed 1722 patients undergoing primary hip or knee replacement surgery. Relevant covariates including demographic data, body mass index, sex, living status and comorbidities were recorded. We assessed joint pain and functional status before surgery and at 3 months and 1 year after surgery using the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores for pain and function. Results: In total, 22.9% (395) of all patients (29.3% of women and 14.1% of men) were living alone at the time of surgery. Compared with patients who lived with another person, those who lived alone were significantly older, had greater comorbidity and reported greater joint pain and dysfunction before surgery and 3 months and 1 year after surgery. Living alone and female sex independently predicted a greater preoperative WOMAC score, and living alone predicted an older age at the time of surgery and a poorer 1-year outcome. Conclusion: Patients who live alone may delay joint replacement surgery until an older age and have greater joint pain and dysfunction than those who live with another person, leading to poorer 1-year outcomes. Contexte : Des etudes ont demontre que les femmes se presentent en chirurgie a un age plus avance et atteintes de dysfonctions plus importantes que les hommes, mais l'explication de cette constatation n'est pas claire. Nous avons etudie l'effet de la situation de vie (personne vivant seule ou avec quelqu'un d'autre) et du sexe au moment d'une arthroplastie de la hanche et du genou, ainsi que les resultats de l'intervention. Methodes : Nous avons sonde 1722 patients qui ont subi une arthroplastie primaire de la hanche ou du genou. On a consigne des covariables pertinentes comme les donnees demographiques, l'indice de masse corporelle, le sexe, la situation de vie et la presence de comorbidites. On a evalue la douleur articulaire et l'etat fonctionnel avant l'intervention chirurgicale, ainsi que trois mois et un an apres celle-ci, en utilisant les resultats selon l'indice Western Ontario et McMaster sur l'arthrose (WOMAC) pour la douleur et le fonctionnement. Resultats : Au total, 22,9 % (395) des patients (29,3 % des femmes et 14,1 % des hommes) vivaient seuls au moment de l'intervention chirurgicale. Comparativement aux patients qui vivaient avec quelqu'un d'autre, ceux qui vivaient seuls etaient beaucoup plus ages, presentaient une comorbidite plus importante et ont signale une douleur articulaire et un dysfonctionnement plus importants au moment de l'intervention chirurgicale, ainsi que trois mois et un an apres celle-ci. Le fait de vivre seul et le sexe feminin constituaient des predicteurs independants d'un resultat WOMAC preoperatoire plus eleve; le fait de vivre seul etait aussi un predicteur d'un age plus eleve au moment de l'intervention chirurgicale et d'un resultat moins bon un an apres celle-ci. Conclusion : Les patients qui vivent seuls peuvent reporter une arthroplastie jusqu'a ce qu'ils soient plus ages et que la douleur articulaire et le dysfonctionnement soient plus importants que ceux qui vivent avec quelqu'un d'autre, ce qui produit des resultats moins bons un an apres l'intervention., Statistics Canada and the United States census both reported in 2006 that 26% of all homes were single-person households. (1,2) A greater number of women than men live alone. (1,2) [...]

Background: Most joint-replacement surgeries are currently performed in community hospitals. We sought to determine whether the functional outcomes of joint-replacement surgery differ between academic and community hospitals. Methods: We surveyed 471 patients for demographic data, Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores and Medical Outcomes Study Short Form 36 (SF-36) scores at baseline and at 3-month and 1-year follow-up. We assessed patient satisfaction at 1 year with a single survey question. Results: Community hospital patients (n = 269) were significantly older and had greater comorbidity than academic hospital patients (n = 202; p < 0.05). We found no difference in WOMAC scores, SF-36 scores or in patient satisfaction between hospitals at 1-year follow-up (p > 0.05). Adjusted analysis showed that patients undergoing surgery in an academic or community hospitals have the same functional outcomes. Conclusion: There is no significant difference in the functional outcomes of joint-replacement surgery between academic and community hospitals. Further work will involve evaluating cost of care differences between these types of hospitals. Contexte : La plupart des arthroplasties sont actuellement pratiquees dans des hopitaux communautaires. Nous avons cherche a determiner si les resultats fonctionnels de l&apos;arthroplastie different entre les hopitaux universitaires et les hopitaux communautaires. Methodes : Nous avons sonde 471 patients pour obtenir leurs donnees demographiques, les resultats selon l&apos;indice Western Ontario et McMaster sur l&apos;arthrose (WOMAC) et les resultats du questionnaire abrege 36 (SF-36) de l&apos;etude sur les resultats medicaux au depart et au suivi a 3 mois et a 1 an. Nous avons evalue la satisfaction des patients a 1 an en leur posant une seule question. Resultats : Les patients des hopitaux communautaires (n = 269) etaient beaucoup plus ages et avaient plus de comorbidites que ceux des hopitaux universitaires (n = 202; p < 0,05). Nous n&apos;avons constate aucune difference au niveau des scores WOMAC et SF-36, de meme qu&apos;au niveau de la satisfaction des patients entre les hopitaux au suivi a 1 an (p > 0,05). L&apos;analyse rajustee a montre que les patients qui ont subi leur intervention dans un hopital universitaire ou communautaire ont les memes resultats fonctionnels. Conclusion : Il n&apos;y a pas de differences importantes au niveau des resultats fonctionnels de l&apos;arthroplastie pratiquee dans les hopitaux universitaires et les hopitaux communautaires. Une etude plus poussee consistera a evaluer les differences au niveau du cout des soins entre ces types d&apos;hopitaux., Total joint arthroplasty (TJA) has been shown to be an effective procedure for relieving pain and improving quality of life. (1-3) Literature from both the United States and Canada projects [...]

Background: Total joint arthroplasty is a highly efficacious and cost-effective procedure for moderate to severe arthritis in the hip and knee. Although patient characteristics are considered to be important determinants [...]

Objective: Increased wait times for total joint arthroplasty (TJA) are a concern nationally and provincially. Additionally, the number of patients requiring revision of their initial TJA is increasing. The purpose [...]