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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]

BackgroundThe purpose of this study was to evaluate outcomes for older persons post-hip fracture repair, including those with cognitive impairment (CI), following implementation of a novel model of care - the Patient-Centered Rehabilitation Model including persons with CI (PCRM-CI). The PCRM-CI is an interdisciplinary rehabilitation program that incorporates education for healthcare professionals (HCPs), including nurses, which is focused on geriatric care including management of dementia and delirium, support for HCPs from an Advanced Practice Nurse, and family support and education. Primary outcome measures were mobility gain from admission to discharge and whether or not patients returned home post-discharge.MethodsThe PCRM-CI intervention was evaluated using a quasi-experimental design, following implementation in two community hospital inpatient rehabilitation units. One hundred forty-nine patients aged 65 and older participated as patients in the usual care (76) or PCRM-CI intervention (73) groups. Patient mobility was assessed at admission and discharge by the Functional Independence Measure Motor Subscale (FIMM); the difference in mobility scores was defined as mobility gain. Patient discharge location was also captured to determine whether or not patients returned home from inpatient rehabilitation.ResultsNo difference in mobility gain was found between the usual care and PCRM-CI groups as measured by the FIMM. Patients in the intervention group were more likely to return home post-discharge than those in the usual care group (p = 0.02).ConclusionsResults of the PCRM-CI evaluation suggest that older adults with CI can successfully be rehabilitated post-hip fracture repair using this novel, interdisciplinary rehabilitation program.

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: Demand for surgery to treat osteoarthritis (OA) of the hip, knee and spine has risen dramatically. Whereas total hip (THA) and total knee arthroplasty (TKA) have been widely accepted as cost-effective, spine surgeries (decompression, decompression with fusion) to treat degenerative conditions remain underfunded compared with other surgeries. Methods: An incremental cost-utility analysis comparing decompression and decompression with fusion to THA and TKA, from the perspective of the provincial health insurance system, was based on an observational matched-cohort study of prospectively collected outcomes and retrospectively collected costs. Patient outcomes were measured using short-form (SF)-36 surveys over a 2-year follow-up period. Utility was modelled over the lifetime, and quality-adjusted life years (QALYs) were determined. We calculated the incremental cost per QALY gained by estimating mean incremental lifetime costs and QALYs of surgery compared with medical management of each diagnosis group after discounting costs and QALYs at 3%. Sensitivity analyses were also conducted. Results: The lifetime incremental cost:utility ratios (ICURs) discounted at 3% were $5321 per QALY for THA, $11 275 per QALY for TKA, $2307 per QALY for spinal decompression and $7153 per QALY for spinal decompression with fusion. The sensitivity analyses did not alter the ranking of the lifetime ICURs. Conclusion: In appropriately selected patients with leg-dominant symptoms secondary to focal lumbar spinal stenosis who have failed medical management, the lifetime ICUR for surgical treatment of lumbar spinal stenosis is similar to those of THA and TKA for the treatment of OA. Contexte : La demande en chirurgie de traitement de l'arthrose de la hanche et du genou a considerablement augmente. Les interventions pour prothese totale de hanche (PTH) et prothese totale du genou (PTG) sont largement reconnues pour leur rapport cout:efficacite, mais les chirurgies de la colonne (decompression, decompression avec arthrodese) pour le traitement des maladies degeneratives restent sousfinancees comparativement aux autres chirurgies. Methodes : Nous avons adopte l'angle du regime d'assurance sante provincial pour effectuer une analyse comparative du rapport cout:utilite differentiel entre la decompression et la decompression avec arthrodese, d'une part, et la PTH et la PTG, d'autre part, a partir des resultats regroupes de facon prospective et des couts regroupes de facon retrospective dans une cohorte d'observation assortie. Les resultats chez les patients ont ete mesures au moyen de questionnaires SF-36 sur une periode de suivi de 2 ans. Le volet utilite a quant a lui ete modelise pour la vie durant et on a calcule le nombre d'annees de vie ajustees en fonction de la qualite (AVAQ). Nous avons aussi calcule le cout differentiel par AVAQ gagnee en estimant les couts differentiels moyens pour la vie durant, et le nombre d'AVAQ associe a la chirurgie par opposition a une prise en charge medicale de chaque diagnostic apres actualisation des couts et des AVAQ a 3 %. Nous avons aussi realise des analyses de sensibilite. Resultats : Les rapports cout:utilite differentiels pour la vie durant actualises a 3 % ont ete de 5 321 $ par AVAQ pour la PTH, de 11 275 $ par AVAQ pour la PTG, de 2 307 $ par AVAQ pour la decompression medullaire et de 7 153 $ par AVAQ pour la decompression medullaire avec arthrodese. Les analyses de sensibilite n'ont pas modifie le classement des rapports cout:utilite differentiels pour la vie durant. Conclusion : Chez certains patients selectionnes ayant des symptomes principalement a une jambe par suite d'une stenose medullaire lombaire focale et pour qui le traitement medical a echoue, l'augmentation du rapport cout:utilite differentiel pour la vie durant avec le traitement chirurgical de la stenose medullaire lombaire est semblable a celui des PTH et PTG pour le traitement de l'arthrose., Osteoarthritis (OA) is the main cause of disability in the elderly population (1) and has a major impact on functional capacity. (2) The prevalence of this degenerative condition is increasing [...]