Association of peri-operative prescription of non-steroidal anti-inflammatory drugs with continued prescription of opioids after total knee arthroplasty: a retrospective claims-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre-clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri-operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90-180 days in previously opioid-naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid-naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri-operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri-operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736-patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri-operative NSAID prescription within 30 days was 1.32 (1.30-1.35), p < 0.001; and 1.12 (1.10-1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre-existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population-based cohort study suggests that peri-operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision-making for post-surgical pain management, risk-benefit discussions with patients and future research.

A prospective randomized clinical trial to evaluate the impact of intraoperative ventilation with high oxygen content on the extent of postoperative pneumocephalus in patients undergoing craniotomies.

Purpose of the article: To determine whether intraoperative ventilation with pure oxygen during the last stage of surgery reduces the occurrence and volume of postoperative pneumocephalus when compared to conventional air/oxygen mixture in patients undergoing craniotomy. MATERIAL AND METHODS: prospective randomized single-blinded study to compare the rate of occurrence and volume of postoperative pneumocephalus in patients undergoing craniotomy receiving intraoperative ventilation with pure oxygen (Group B) versus a conventional air/oxygen 1:1 mixture (Group A) during the last stage of surgery. This trial was registered in ClinicalTrials.gov #NCT02722928, protocol number 2015H0032. RESULTS: One hundred patients were randomized into group 'A' and group 'B'. Seventy patients were included in the final analysis with 39 patients allocated in group 'A' and 31 patients in group 'B'. Median and IQR were used for postoperative penumocephalus volume. Group A: 9.65 [3.61-23.20]; Group B: 7.06 [2.70-20.1]. Our study showed no prophylactic effect on postoperative pneumocephalus volume when using mechanical ventilation with higher oxygen concentrations than the standard FiO2 during the last stage of surgery in patients undergoing craniotomy (p = .47). No statistical difference was found in SICU LOS between groups (median 1,380 min [group A] versus 1,524 min [group B]; p = .18). CONCLUSION: The use of intraoperative mechanical ventilation with pure oxygen was not associated with a prophylactic effect on the occurrence and extent of postoperative pneumocephalus in our patient setting. Published literature describing the extent of postoperative pneumocephalus is limited or highly variable among institutions.

Pleiotropic Effects of Statins: Untapped Potential for Statin Pharmacotherapy.

BACKGROUND: Statins are effective for primary and secondary prevention of atherosclerotic cardiovascular disease. They also have systemic anti-inflammatory and immunomodulating properties suggesting potential utility for improving clinical outcomes for a wide range of diseases. The literature provides data suggesting benefit in patients with comorbidities associated with contrast-induced nephropathy (CIN), chronic obstructive pulmonary disease (COPD), pneumonia, head injury, neurological disease (e.g. Alzheimer's and Parkinson's disease), prostate cancer, nuclear cataract and spinal cord injury. This systematic review evaluates the current evidence supporting the potential benefit of statins outside their customary role of attenuating cardiovascular risk reduction. METHODS: The electronic databases MEDLINE, EMBASE, and clinicaltrials.gov were searched for studies published January 2000 - March 2018 reporting comorbidity reduction associated with statin use. RESULTS: Fifty-eight publications that satisfied our selection criteria (based on the PRISM guidance for systematic reviews) were selected and included case-control, cohort, cross-sectional and observational studies as well as systematic reviews and meta-analyses. Ten studies addressed statin use and incidence of CIN after coronary imaging; 8 addressed statin use in patients with COPD; 14 addressed statin use and comorbidity reduction associated with head injury and/or a neurological disease disorder; 5 addressed the association between statin use and nuclear cataract; 9 addressed the association between statin use and prostate/colorectal cancer; 9 studies addressed the role of statin use in treating infections; and 3 addressed the association between statin use and spinal cord injury related survival rate. CONCLUSION: Overall, the literature supports beneficial pleiotropic effects of statin use in contrastinduced nephropathy, head injury, Alzheimer's and Parkinson's disease, nuclear cataract, prostate cancer, infection management, and spinal cord injury. Further investigation is warranted, and randomized clinical trials are needed to confirm the clinical utility suggested by the reported studies included in this meta-analysis.

Critical role of NKT cells in posttransplant alloantibody production.

We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+ CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing natural killer T cells (NKT cells) contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient WT, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was interferon-γ-dependent and IL-4-independent. Cognate interactions between type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+ CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli.

Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab.

BACKGROUND: Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab. METHODS: Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models. RESULTS: A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02-1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed. CONCLUSIONS: Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients.