Causes and predictors of failed same-day home discharge following primary hip and knee total joint arthroplasty: a Canadian perspective.

PURPOSE: Same-day home (SDH) discharge in total joint arthroplasty (TJA) has increased in popularity in recent years. The objective of this study was to evaluate the causes and predictors of failed discharges in planned SDH patients. METHODS: A consecutive cohort of patients who underwent total knee (TKA) or total hip arthroplasty (THA) that were scheduled for SDH discharge between 01 April 2019 and 31 March 2021 were retrospectively reviewed. Patient demographics, causes of failed discharge, perioperative variables, 30-day readmissions and 6-month reoperation rates were collected. Multivariate regression analysis was undertaken to identify independent predictors of failed discharge. RESULTS: The cohort consisted of 527 consecutive patients. 101 (19%) patients failed SDH discharge. The leading causes were postoperative hypotension (20%) and patients who were ineligible for the SDH pathway (19%). 2 individual surgeons, later operative start time (OR 1.3; 95% CI, 1.15-1.55; p = 0.001), ASA class IV (OR 3.4; 95% CI, 1.4-8.2; p = 0.006) and undergoing a THA (OR 2.0; 95% CI, 1.2-3.1, p = 0.004) were independent predictors of failed SDH discharge. No differences in age, BMI, gender, surgical approach or type of anaesthetic were found (p > 0.05). The 30-day readmission or 6-month reoperation were similar between groups (p > 0.05). CONCLUSIONS: Hypotension and inappropriate patient selection were the leading causes of failed SDH discharge. Significant variability existed between individual surgeons failed discharge rates. Patients undergoing a THA, classified as ASA IV or had a later operative start time were all more likely to fail SDH discharge.

Getting fit for hip and knee replacement: a protocol for the Fit-Joints pilot randomized controlled trial of a multi-modal intervention in frail patients with osteoarthritis.

BACKGROUND: Joint replacement provides significant improvements in pain, physical function, and quality of life in patients with osteoarthritis. With a growing body of evidence indicating that frailty can be treated, it is important to determine whether targeting frailty reduction in hip and knee replacement patients improves post-operative outcomes. OBJECTIVES: The primary objective is to examine the feasibility of a parallel group RCT comparing a preoperative multi-modal frailty intervention to usual care in pre-frail/frail older adults undergoing elective unilateral hip or knee replacements. The secondary objectives areTo explore potential efficacy of the multi-modal frailty intervention in improving frailty and mobility between baseline and 6 weeks post-surgery using Fried frailty phenotype and short performance physical battery (SPPB) respectively.To explore potential efficacy of the multi-modal frailty intervention on post-operative healthcare services use. METHODS/DESIGN: In a parallel group pilot RCT, participants will be recruited from the Regional Joint Assessment Program in Hamilton, Canada. Participants who are (1) ≥ 60 years old; (2) pre-frail (score of 1 or 2) or frail (score of 3-5; Fried frailty phenotype); (3) having elective unilateral hip or knee replacement; and (4) having surgery wait times between 3 and 10 months will be recruited and randomized to either the intervention or usual care group. The multi-modal frailty intervention components will include (1) tailored exercise program (center-based and/or home-based) with education and cognitive behavioral change strategies; (2) protein supplementation; (3) vitamin D supplementation; and (4) medication review. The main comparative analysis will take place at 6 weeks post-operative. The outcome assessors, data entry personnel, and data analysts are blinded to treatment allocation. Assessments: feasibility will be assessed by recruitment rate, retention rate, and data collection completion. Frailty and healthcare use and other clinical outcomes will be assessed. The study outcomes will be collected at the baseline, 1 week pre-operative, and 6 weeks and 6 months post-operative. DISCUSSION: This is the first study to examine the feasibility of multi-modal frailty intervention in pre-frail/frail older adults undergoing hip or knee replacement. This study will inform the planning and designing of multi-modal frailty interventional studies in hip and knee replacement patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02885337.

Randomized controlled trial of gabapentin as an adjunct to perioperative analgesia in total hip arthroplasty patients.

PURPOSE: Gabapentin was investigated as a single-dose adjunct to morphine for postoperative pain management. The primary objective was to determine if gabapentin given preoperatively and for two days postoperatively as part of multimodal analgesia would decrease postoperative morphine consumption in patients undergoing primary total hip arthroplasty (THA). METHODS: The study group included 102 patients aged 19-90 years who were undergoing primary THA in a single joint with no contraindications to the study medications, no chronic pain syndrome, and no chronic opioid use. Intervention group patients (n = 48) received gabapentin 600 mg po preoperatively and 200 mg postoperatively on the day of surgery. They were continued on gabapentin at 200 mg three times daily for two days. Control group patients (n = 54) received placebo in a similar fashion. Preoperatively, all patients were given 30 mg of ketorolac intravenously and acetaminophen 1000 mg po. Postoperatively, they received intravenous patient-controlled analgesia with morphine, along with ketorolac 15 mg iv and acetaminophen 1000 mg po every six hours. RESULTS: The primary outcome was mean (SD) postoperative morphine consumption at 72 hr which was 55.8 (39.2) mg in the gabapentin groups vs 60.7 (37.2) mg for the control group (mean difference, -4.91 mg, 95% confidence intervals [CI]: -21.2 to 11.35; P = 0.550). There were no significant differences between the groups regarding secondary outcomes: pain scores, side effects, range of motion. Patient satisfaction on day 3 was more favourable in the placebo group. Length of hospitalization was marginally shorter in the placebo group. CONCLUSIONS: This trial indicated that gabapentin treatment had no clinically important reduction in postoperative morphine consumption at 72 hr in patients undergoing THA. Multimodal analgesia may account for the similar primary and secondary outcomes found in the groups. This trial was registered at ClinicalTrials.gov, number: NCT01307202.

Reanalysis of morphine consumption from two randomized controlled trials of gabapentin using longitudinal statistical methods.

BACKGROUND: Postoperative pain management in total joint replacement surgery remains ineffective in up to 50% of patients and has an overwhelming impact in terms of patient well-being and health care burden. We present here an empirical analysis of two randomized controlled trials assessing whether addition of gabapentin to a multimodal perioperative analgesia regimen can reduce morphine consumption or improve analgesia for patients following total joint arthroplasty (the MOBILE trials). METHODS: Morphine consumption, measured for four time periods in patients undergoing total hip or total knee arthroplasty, was analyzed using a linear mixed-effects model to provide a longitudinal estimate of the treatment effect. Repeated-measures analysis of variance and generalized estimating equations were used in a sensitivity analysis to compare the robustness of the methods. RESULTS: There was no statistically significant difference in morphine consumption between the treatment group and a control group (mean effect size estimate 1.0, 95% confidence interval -4.7, 6.7, P=0.73). The results remained robust across different longitudinal methods. CONCLUSION: The results of the current reanalysis of morphine consumption align with those of the MOBILE trials. Gabapentin did not significantly reduce morphine consumption in patients undergoing major replacement surgeries. The results remain consistent across longitudinal methods. More work in the area of postoperative pain is required to provide adequate management for this patient population.

Empirical comparison of four baseline covariate adjustment methods in analysis of continuous outcomes in randomized controlled trials.

BACKGROUND: Although seemingly straightforward, the statistical comparison of a continuous variable in a randomized controlled trial that has both a pre- and posttreatment score presents an interesting challenge for trialists. We present here empirical application of four statistical methods (posttreatment scores with analysis of variance, analysis of covariance, change in scores, and percent change in scores), using data from a randomized controlled trial of postoperative pain in patients following total joint arthroplasty (the Morphine COnsumption in Joint Replacement Patients, With and Without GaBapentin Treatment, a RandomIzed ControlLEd Study [MOBILE] trials). METHODS: Analysis of covariance (ANCOVA) was used to adjust for baseline measures and to provide an unbiased estimate of the mean group difference of the 1-year postoperative knee flexion scores in knee arthroplasty patients. Robustness tests were done by comparing ANCOVA with three comparative methods: the posttreatment scores, change in scores, and percentage change from baseline. RESULTS: All four methods showed similar direction of effect; however, ANCOVA (-3.9; 95% confidence interval [CI]: -9.5, 1.6; P=0.15) and the posttreatment score (-4.3; 95% CI: -9.8, 1.2; P=0.12) method provided the highest precision of estimate compared with the change score (-3.0; 95% CI: -9.9, 3.8; P=0.38) and percent change (-0.019; 95% CI: -0.087, 0.050; P=0.58). CONCLUSION: ANCOVA, through both simulation and empirical studies, provides the best statistical estimation for analyzing continuous outcomes requiring covariate adjustment. Our empirical findings support the use of ANCOVA as an optimal method in both design and analysis of trials with a continuous primary outcome.

Gabapentin does not improve multimodal analgesia outcomes for total knee arthroplasty: a randomized controlled trial.

PURPOSE: This study assessed whether gabapentin given preoperatively and for two days postoperatively (in addition to patient-controlled analgesia [PCA] morphine, acetaminophen, and ketorolac) is effective in reducing morphine requirements and moderating pain scores when compared with placebo for primary total knee arthroplasty. METHODS: This single-centre double-blind randomized controlled trial was undertaken in patients who underwent primary total knee arthroplasty. All subjects received acetaminophen 1,000 mg and ketorolac 15 mg po preoperatively. Postoperatively, subjects received PCA morphine, acetaminophen 1,000 mg every six hours, and ketorolac 15 mg po every six hours. Subjects received either gabapentin 600 mg po preoperatively followed by 200 mg po every eight hours for two days or matching placebo. The primary outcome was cumulative morphine consumption at 72 hr following surgery. Secondary outcome measures included pain scores and patient satisfaction. RESULTS: There were 52 subjects in the gabapentin group and 49 subjects in the placebo group. The average cumulative morphine consumption at 72 hr postoperatively was 66.3 mg in the gabapentin group and 72.5 mg in the placebo group (difference -6.2 mg; 95% confidence interval -29.1 to 16.8 mg; P = 0.59). Mean pain scores at rest, with passive movement, or with weight bearing were similar in both groups at corresponding time periods for the first three days following surgery. In addition, mean patient satisfaction scores and hospital length of stay were similar in the two groups. CONCLUSION: Gabapentin 600 mg po given preoperatively followed by 200 mg po every eight hours for two days has no effect on postoperative morphine consumption, pain scores, patient satisfaction, or length of hospital stay. This trial is registered at ClinicalTrials.gov NCT01307202.

Aspirin response variability after major orthopedic surgery.

INTRODUCTION: Variability in platelet response to aspirin has been reported in patients undergoing cardiac surgery but has rarely been described in other operative settings and its mechanism remains uncertain. We performed a prospective cohort study to investigate the variability in platelet response to aspirin and to explore its mechanism in patients undergoing major orthopedic surgery. MATERIALS AND METHODS: Twelve aspirin-treated patients undergoing elective hip or knee replacement were recruited. Once-daily aspirin was continued throughout the perioperative period. We measured platelet function using light transmission aggregation (LTA) in response to arachidonic acid (PL(AA)) and serum thromboxane B(2) (TXB(2)) at baseline (before surgery) as well as on days 1, 2, 3, 4, 5, 6, and 8 after surgery. We defined aspirin low response as a PL(AA)>20%. RESULTS: Six patients exhibited aspirin low response, which typically started on post-operative days 3 or 4; the remaining 6 patients had normal response to aspirin. Compared to aspirin responders, patients with aspirin low response showed significantly higher serum TXB(2) levels, a more pronounced early decrease in platelet count, and a significantly more rapid recovery of the platelet count after surgery. CONCLUSION: Aspirin response variability occurred in patients after major orthopedic surgery, with one-half of the patients in our study exhibiting post-operative aspirin low response. Increased platelet turnover might be a contributor to aspirin response variability after orthopedic surgery.

A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: no advantage of loading doses over daily supplementation.

BACKGROUND: There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels. METHODS: In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD) was measured at baseline, discharge from acute care (approximately 4-weeks), and 3-months. RESULTS: Sixty-five patients were enrolled in the study (44% male). An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15) and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09), respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L), and 44% of the 100,000 group. CONCLUSIONS: In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose) resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D. TRIAL REGISTRATION: Clinical Trials # NCT00424619.

Prevalence of clinically significant improvement following total knee replacement.

OBJECTIVE: Although total knee replacement (TKR) has a high reported success rate, the pain relief and functional improvement after surgery vary. The purpose of our retrospective cohort study was to determine the prevalence of patients showing no clinically important improvement 1 year after TKR, and patient factors that may predict this outcome. METHODS: We reviewed primary TKR registry data that were collected from 2 academic hospitals: the Toronto Western Hospital and the Hamilton Health Sciences Henderson Hospital in Ontario, Canada. Relevant covariates including demographic data, body mass index, and comorbidity were recorded. Knee joint pain and functional status were assessed at baseline and at 1-year followup with the Western Ontario McMaster University Osteoarthritis Index (WOMAC) and Oxford Knee Score (OKS) to measure the change using the minimal clinically important difference (MCID). Logistic regression modeling was used to identify the predictors of interest. RESULTS: Overall, 11.7% (373/3177) of patients reported no clinically important improvement 1 year after surgery. Logistic regression modeling showed that a greater patient age independently predicted no clinically important improvement on the WOMAC scale 1 year after surgery (p = 0.0003), while being male independently predicted no clinically important improvement on the OKS 1 year after surgery (p = 0.008). CONCLUSION: Awareness of the prevalence of patients who may show no clinically important improvement and factors that predict this outcome will help patients and surgeons set realistic expectations of surgery.

Effect of early surgery after hip fracture on mortality and complications: systematic review and meta-analysis.

BACKGROUND: Guidelines exist for the surgical treatment of hip fracture, but the effect of early surgery on mortality and other outcomes that are important for patients remains unclear. We conducted a systematic review and meta-analysis to determine the effect of early surgery on the risk of death and common postoperative complications among elderly patients with hip fracture. METHODS: We searched electronic databases (including MEDLINE and EMBASE), the archives of meetings of orthopedic associations and the bibliographies of relevant articles and questioned experts to identify prospective studies, published in any language, that evaluated the effects of early surgery in patients undergoing procedures for hip fracture. Two reviewers independently assessed methodologic quality and extracted relevant data. We pooled data by means of the DerSimonian and Laird random-effects model, which is based on the inverse variance method. RESULTS: We identified 1939 citations, of which 16 observational studies met our inclusion criteria. These studies had a total of 13 478 patients for whom mortality data were complete (1764 total deaths). Based on the five studies that reported adjusted risk of death (4208 patients, 721 deaths), irrespective of the cut-off for delay (24, 48 or 72 hours), earlier surgery (i.e., within the cut-off time) was associated with a significant reduction in mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68-0.96, p = 0.01). Unadjusted data indicated that earlier surgery also reduced in-hospital pneumonia (RR 0.59, 95% CI 0.37-0.93, p = 0.02) and pressure sores (RR 0.48, 95% CI 0.34-0.69, p < 0.001). INTERPRETATION: Earlier surgery was associated with a lower risk of death and lower rates of postoperative pneumonia and pressure sores among elderly patients with hip fracture. These results suggest that reducing delays may reduce mortality and complications.

Dysfunctional Nrf2-Keap1 redox signaling in skeletal muscle of the sedentary old.

The role of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) redox signaling has not been characterized in human skeletal muscle despite an extensive delineation of oxidative stress in the etiology of aging and sarcopenia. We assessed whether the age-associated decline in antioxidant response is due, at least in part, to dysfunction in Nrf2-Keap1 redox signaling. We also evaluated whether an active lifestyle can conserve skeletal muscle cellular redox status via activation of Nrf2-Keap1 signaling. Here we show that a recreationally active lifestyle is associated with the activation of upstream modulators that induce the Nrf2-mediated antioxidant response cascade in skeletal muscle of the elderly. Conversely, a sedentary lifestyle is negatively associated with these adaptations mainly because of dysregulation of Nrf2-Keap1 redox signaling that renders the intracellular environment prone to reactive oxygen species-mediated toxicity. Our results indicate that an active lifestyle is an important determinant of cellular redox status. We propose that the metabolic induction of Nrf2-Keap1 redox signaling promises to be a viable therapy for attenuating oxidative stress-mediated damage in skeletal muscle associated with physical inactivity.

Aberrant mitochondrial homeostasis in the skeletal muscle of sedentary older adults.

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; female symbol = male symbol). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

Body weight-supported treadmill training for patients with hip fracture: a feasibility study.

UNLABELLED: Giangregorio LM, Thabane L, deBeer J, Farrauto L, McCartney N, Adachi JD, Papaioannou A. Body weight-supported treadmill training for patients with hip fracture: a feasibility study. OBJECTIVE: To determine the feasibility of body weight-supported treadmill training (BWSTT) as a strategy for improving independent ambulation among patients who had sustained a hip fracture. DESIGN: Nonrandomized controlled trial. SETTING: Inpatient rehabilitation. PARTICIPANTS: Patients with a stable hip fracture and at least 50% weight-bearing. INTERVENTION: BWSTT in lieu of standard walking exercises throughout stay in rehabilitation. MAIN OUTCOMES MEASURES: Feasibility outcomes included the number of patients agreeing to participate in treadmill walking, the number who returned for follow-up assessments, compliance, and the number of adverse events. Secondary outcomes included the Lower Extremity Functional Scale, the Timed Up & Go test, a 2-minute walk test, and the Falls Self-Efficacy Scale. Univariate regression was used to assess the group effect on score changes from baseline to discharge and from baseline to follow-up. RESULTS: Among 41 potentially eligible patients, 21 (51%) agreed to participate and 14 returned for follow-up assessments. The recruitment goal of 12 patients agreeing to BWSTT was achieved; however, retention by 3-month follow-up was 67%. The average compliance was 3 sessions a week; however, several patients were below average. No adverse events of BWSTT were reported. There were no significant differences between groups with respect to secondary outcomes. CONCLUSIONS: BWSTT may be a feasible method for retraining gait among patients with hip fracture. However, future studies evaluating its efficacy need rigorous methods for ensuring compliance and retention.

Prevalence of osteoporosis in osteoarthritic patients undergoing total hip or total knee arthroplasty.

OBJECTIVE: To determine the prevalence of osteoporosis in osteoarthritic patients undergoing total hip or total knee arthroplasty. DESIGN: Cross-sectional study. SETTING: The Specialized Outpatient Rehabilitation Service's (SORS) Pre-surgical Arthroplasty Service located at the Chedoke Hospital, Hamilton Health Sciences, Hamilton, ON, Canada. PARTICIPANTS: SORS outpatients (N=364), from the period of March 2006 to March 2007. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Prevalence of osteoporosis was determined by review of a self-reported survey, and defined by (1) self-reported diagnosis of osteoporosis, (2) history of fragility fracture (defined by a bone fracture occurring as a result of a fall from standing height or less after the age of 50), or (3) current treatment for osteoporosis using bisphosphonates. RESULTS: Of the study cohort, 26% were classified as having osteoporosis, according to our criteria. Of the patients with self-reported osteoporosis or a history of fragility fractures, only 37% and 17% reported current treatment with bisphosphonates, respectively. CONCLUSIONS: Osteoporosis is common in the osteoarthritic arthroplasty population, with a prevalence at least equal to that in the general population. Due to the self-reported nature of the study, the prevalence of osteoporosis in this population is likely significantly higher. Results from this study indicate need for further research, specifically in formal assessment for osteoporosis in patients undergoing a joint replacement.

Do patients perceive a link between a fragility fracture and osteoporosis?

BACKGROUND: To evaluate factors associated with whether patients associate their fracture with future fracture risk. METHODS: Fragility fracture patients participated in a telephone interview. Unadjusted odds ratios (OR, [95% CI]) were calculated to identify factors associated with whether patients associate their fracture with increased fracture risk or osteoporosis. Predictors identified in univariate analysis were entered into multivariable logistic regression models. RESULTS: 127 fragility fracture patients (82% female) participated in the study, mean (SD) age 67.5 (12.7) years. An osteoporosis diagnosis was reported in 56 (44%) participants, but only 17% thought their fracture was related to osteoporosis. Less than 50% perceived themselves at increased risk of fracture. The odds of an individual perceiving themselves at increased risk for fracture were higher for those that reported a diagnosis of osteoporosis (OR 22.91 [95%CI 7.45;70.44], p < 0.001), but the odds decreased with increasing age (0.95 [0.91;0.99], p<0.009). The only variable significantly associated with the perception that the fracture was related to osteoporosis was self-reported osteoporosis diagnosis (39.83 [8.15;194.71], p<0.001). CONCLUSION: Many fragility fracture patients do not associate their fracture with osteoporosis. It is crucial for physicians to communicate to patients that an osteoporosis diagnosis, increasing age or a fragility fracture increases the risk for future fracture.