Is the Preoperative Use of Antidepressants and Benzodiazepines Associated with Opioid and Other Analgesic Use After Hip and Knee Arthroplasty?

BACKGROUND: Mental health disorders can occur in patients with pain conditions, and there have been reports of an increased risk of persistent pain after THA and TKA among patients who have psychological distress. Persistent pain may result in the prolonged consumption of opioids and other analgesics, which may expose patients to adverse drug events and narcotic habituation or addiction. However, the degree to which preoperative use of antidepressants or benzodiazepines is associated with prolonged analgesic use after surgery is not well quantified. QUESTION/PURPOSES: (1) Is the preoperative use of antidepressants or benzodiazepine medications associated with a greater postoperative use of opioids, NSAIDs, or acetaminophen? (2) Is the proportion of patients still using opioid analgesics 1 year after arthroplasty higher among patients who were taking antidepressants or benzodiazepine medications before surgery, after controlling for relevant confounding variables? (3) Does analgesic drug use decrease after surgery in patients with a history of antidepressant or benzodiazepine use? (4) Does the proportion of patients using antidepressants or benzodiazepines change after joint arthroplasty compared with before? METHODS: Of the 10,138 patients who underwent hip arthroplasty and the 9930 patients who underwent knee arthroplasty at Coxa Hospital for Joint Replacement, Tampere, Finland, between 2002 and 2013, those who had primary joint arthroplasty for primary osteoarthritis (64% [6502 of 10,138] of patients with hip surgery and 82% [8099 of 9930] who had knee surgery) were considered potentially eligible. After exclusion of another 8% (845 of 10,138) and 13% (1308 of 9930) of patients because they had revision or another joint arthroplasty within 2 years of the index surgery, 56% (5657 of 10,138) of patients with hip arthroplasty and 68% (6791 of 9930) of patients with knee arthroplasty were included in this retrospective registry study. Patients who filled prescriptions for antidepressants or benzodiazepines were identified from a nationwide drug prescription register, and information on the filled prescriptions for opioids (mild and strong), NSAIDs, and acetaminophen were extracted from the same database. For the analyses, subgroups were created according to the status of benzodiazepine and antidepressant use during the 6 months before surgery. First, the proportions of patients who used opioids and any analgesics (that is, opioids, NSAIDs, or acetaminophen) were calculated. Then, multivariable logistic regression adjusted with age, gender, joint, Charlson Comorbidity Index, BMI, laterality (unilateral/same-day bilateral), and preoperative analgesic use was performed to calculate odds ratios for any analgesic use and opioid use 1 year postoperatively. Additionally, the proportion of patients who used antidepressants and benzodiazepines was calculated for 2 years before and 2 years after surgery. RESULTS: At 1 year postoperatively, patients with a history of antidepressant or benzodiazepine use were more likely to fill prescriptions for any analgesics than were patients without a history of antidepressant or benzodiazepine use (adjusted odds ratios 1.9 [95% confidence interval 1.6 to 2.2]; p < 0.001 and 1.8 [95% CI 1.6 to 2.0]; p < 0.001, respectively). Similarly, patients with a history of antidepressant or benzodiazepine use were more likely to fill prescriptions for opioids than patients without a history of antidepressant or benzodiazepine use (adjusted ORs 2.1 [95% CI 1.7 to 2.7]; p < 0.001 and 2.0 [95% CI 1.6 to 2.4]; p < 0.001, respectively). Nevertheless, the proportion of patients who filled any analgesic prescription was smaller 1 year after surgery than preoperatively in patients with a history of antidepressant (42% [439 of 1038] versus 55% [568 of 1038]; p < 0.001) and/or benzodiazepine use (40% [801 of 2008] versus 55% [1098 of 2008]; p < 0.001). The proportion of patients who used antidepressants and/or benzodiazepines was essentially stable during the observation period. CONCLUSION: Surgeons should be aware of the increased risk of prolonged opioid and other analgesic use after surgery among patients who were on preoperative antidepressant and/or benzodiazepine therapy, and they should have candid discussions with patients referred for elective joint arthroplasty about this possibility. Further studies are needed to identify the most effective methods to reduce prolonged postoperative opioid use among these patients. LEVEL OF EVIDENCE: Level III, therapeutic study.acceptedVersionPeer reviewe

Infection after primary hip arthroplasty: A comparison of 3 Norwegian health registers

Background and purpose: The aim of the present study was to assess incidence of and risk factors for infection after hip arthroplasty in data from 3 national health registries. We investigated differences in risk patterns between surgical site infection (SSI) and revision due to infection after primary total hip arthroplasty (THA) and hemiarthroplasty (HA). Materials and methods: This observational study was based on prospective data from 2005–2009 on primary THAs and HAs from the Norwegian Arthroplasty Register (NAR), the Norwegian Hip Fracture Register (NHFR), and the Norwegian Surveillance System for Healthcare–Associated Infections (NOIS). The Norwegian Patient Register (NPR) was used for evaluation of case reporting. Cox regression analyses were performed with revision due to infection as endpoint for data from the NAR and the NHFR, and with SSI as the endpoint for data from the NOIS. Results: The 1–year incidence of SSI in the NOIS was 3.0% after THA (167/5,540) and 7.3% after HA (103/1,416). The 1–year incidence of revision due to infection was 0.7% for THAs in the NAR (182/24,512) and 1.5% for HAs in the NHFR (128/8,262). Risk factors for SSI after THA were advanced age, ASA class higher than 2, and short duration of surgery. For THA, the risk factors for revision due to infection were male sex, advanced age, ASA class higher than 1, emergency surgery, uncemented fixation, and a National Nosocomial Infection Surveillance (NNIS) risk index of 2 or more. For HAs inserted after fracture, age less than 60 and short duration of surgery were risk factors of revision due to infection. Interpretation: The incidences of SSI and revision due to infection after primary hip replacements in Norway are similar to those in other countries. There may be differences in risk pattern between SSI and revision due to infection after arthroplasty. The risk patterns for revision due to infection appear to be different for HA and THA

Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex

Objectives Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage-mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures. Methods A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion. Results We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis. Conclusion These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific.Peer reviewe

One-year functional outcomes of patients aged 80 years or more undergoing colonic cancer surgery: prospective, multicentre observational study

Background: Older patients are at high risk of experiencing delayed functional recovery after surgical treatment. This study aimed to identify factors that predict changes in the level of support for activities of daily living and mobility 1 year after colonic cancer surgery.Methods: This was a multicentre, observational study conforming to STROBE guidelines. The prospective data included pre-and postoperative mobility and need for support in daily activities, co-morbidities, onco-geriatric screening tool (G8), clinical frailty scale (CFS), operative data, and postoperative surgical outcomes.Results: A total of 167 patients aged 80 years or more with colonic cancer were recruited. After surgery, 30 per cent and 22 per cent of all patients had increased need for support and decreased motility. Multivariableanalysis with all patients demonstrated that preoperative support in daily activities outside the home (OR 3.23, 95 per cent c.i. 1.06 to 9.80, P = 0.039) was associated with an increased support at follow-up. A history of cognitive impairment (3.15, 1.06 to 9.34, P = 0.038) haemoglobin less than 120 g/l (7.48, 1.97 to 28.4, P = 0.003) and discharge to other medical facilities (4.72, 1.39 to 16.0, P = 0.013) were independently associated with declined mobility. With functionally independent patients, haemoglobin less than 120 g/l (8.31, 1.76 to 39.2, P = 0.008) and discharge to other medical facilities (4.38, 1.20 to 16.0, P = 0.026) were associated with declined mobility.Conclusion: Increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicts an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should focus on anaemia correction, nutritional status, and mobility with detailed rehabilitation plan.Greater increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicted an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should especially focus on anaemia correction, nutritional status, and mobility with a detailed rehabilitation plan.</p