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Low‐grade inflammation is considered as a pathophysiological mechanism in a subtype of patients with major depressive disorder (MDD). Anti‐inflammatory drugs have shown efficacy in treating MDD. However, it remains unclear how to identify suitable patients for anti‐inflammatory treatment of depression. This study investigates the predictive value of pre‐treatment high‐sensitivity C‐Reactive Protein (hsCRP) stratification on the outcome of celecoxib augmentation of vortioxetine. The PREDDICT study was conducted as a randomized, double‐blind, placebo‐controlled 6‐week trial on augmentation of vortioxetine with celecoxib between December 2017 and April 2020 at the University of Adelaide (Australia). The present analysis focusses on the question of whether the pre‐treatment hsCRP measurement and stratification of patients to depression with inflammation (hsCRP >3 mg/L) or without inflammation (hsCRP ≤3 mg/L) has an impact on the outcome of anti‐inflammatory treatment with celecoxib. A total of n = 119 mostly treatment‐resistant MDD patients with moderate to severe symptomatology were recruited in the trial. There was no effect of treatment group (celecoxib or placebo), pre‐treatment hsCRP strata (with/without inflammation), or interaction between the two terms on treatment outcome. The results of the current analysis do not support the hypothesis that pre‐treatment hsCRP level is predictive for response to anti‐inflammatory treatment with celecoxib in MDD patients. Further research is needed to identify appropriate biomarkers for the prediction of anti‐inflammatory treatment outcome in depression. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p. [ABSTRACT FROM AUTHOR]

This article discusses a study on factors influencing blood transfusion in adolescent idiopathic scoliosis correction surgery. The authors raise concerns about certain aspects of the study's methodology and analysis. They highlight the need for standardized protocols for fluid management, including the use of esophageal doppler monitoring. The authors also question the exclusion of certain known risk factors from the statistical model and suggest that further research with a larger sample size is needed. Overall, caution should be exercised when applying the current findings in clinical practice. [Extracted from the article]

We examined systems-level costs before and after the implementation of an emergency department paediatric sepsis screening, recognition and treatment pathway. Aggregated hospital admissions for all children aged < 18y with a diagnosis code of sepsis upon admission in Queensland, Australia were compared for 16 participating and 32 non-participating hospitals before and after pathway implementation. Monte Carlo simulation was used to generate uncertainty intervals. Policy impacts were estimated using difference-in-difference analysis comparing observed and expected results. We compared 1055 patient episodes before (77.6% in-pathway) and 1504 after (80.5% in-pathway) implementation. Reductions were likely for non-intensive length of stay (− 20.8 h [− 36.1, − 8.0]) but not intensive care (–9.4 h [− 24.4, 5.0]). Non-pathway utilisation was likely unchanged for interhospital transfers (+ 3.2% [− 5.0%, 11.4%]), non-intensive (− 4.5 h [− 19.0, 9.8]) and intensive (+ 7.7 h, [− 20.9, 37.7]) care length of stay. After difference-in-difference adjustment, estimated savings were 596 [277, 942] non-intensive and 172 [148, 222] intensive care days. The program was cost-saving in 63.4% of simulations, with a mean value of $97,019 [− $857,273, $1,654,925] over 24 months. A paediatric sepsis pathway in Queensland emergency departments was associated with potential reductions in hospital utilisation and costs. [ABSTRACT FROM AUTHOR]

Background Partial response to antidepressant medication as well as relapse and treatment resistance are common in major depressive disorder (MDD). Therefore, for most patients with MDD, there will be a need to consider changing antidepressant medication at some stage during the course of the illness. The PREDDICT study investigates the efficacy of augmenting vortioxetine with celecoxib. Methods We describe the method used in the PREDDICT study to change participants, who were already taking antidepressant medication at the time of the screening visit, to vortioxetine. We used a cross-titration to change study participants to vortioxetine. Results Of a total of 122 study participants who were randomized to receive vortioxetine plus celecoxib or vortioxetine plus placebo at the study baseline visit, 82 were taking antidepressant medication (other than vortioxetine) prior to randomization. These medications were selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants, mirtazapine, or agomelatine. Eighty of these 82 participants completed the changeover to vortioxetine as well as the study baseline visit. We found side effects were generally mild during this changeover period. In addition, there was a reduction in mean total Montgomery-Åsberg Depression Rating Scale score of 2.5 (SD 6.0) from study baseline to week 2 and a further reduction in mean total Montgomery-Åsberg Depression Rating Scale of 2.5 (SD 5.9) from week 2 to week 4. Conclusion Changing other antidepressants to vortioxetine can be done safely and was generally well-tolerated. However, there are some antidepressant classes, in particular monoamine oxidase inhibitors that require a washout period, which were not represented in this study. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR); ID number 12617000527369p; http://www.anzctr.org.au/ACTRN12617000527369p.aspx [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a highly prevalent condition with a substantial incidence of relapse or treatment resistance. A subset of patients show evidence of low-grade inflammation, with these patients having a higher likelihood of more severe or difficult to treat courses of illness. Anti-inflammatory treatment of MDD has been investigated with mixed results, and no known studies have included assessments beyond cessation of the anti-inflammatory agent, meaning it remains unknown if any benefit from treatment persists. The objective of the present study was to investigate treatment outcomes up to 29 weeks post-cessation of celecoxib or placebo augmentation of an antidepressant, and how concentrations of selected inflammatory markers change over the same period., Methods: The PREDDICT parallel-group, randomised, double-blind, placebo-controlled trial (University of Adelaide, Australia) ran from December 2017 to April 2020. Participants with MDD were stratified into normal range or elevated inflammation strata according to screening concentrations of high sensitivity C-reactive protein (hsCRP). Participants were randomised to treatment with vortioxetine and celecoxib or vortioxetine and placebo for six weeks, and vortioxetine alone for an additional 29 weeks (35 total weeks). Following a previous publication of results from the six-week RCT phase, exploratory analyses were performed on Montgomery-Åsberg Depression Rating Scale (MADRS) scores, response and remission outcomes, and selected peripheral inflammatory markers across the entire study duration up to week 35., Results: Participants retained at each observation were baseline N=119, week 2 N=115, week 4 N=103, week 6 N=104, week 8 N=98, week 22 N=81, and week 35 N=60. Those in the elevated hsCRP celecoxib-augmented group had a statistically significantly greater reduction in MADRS score from baseline to week 35 compared to all other groups, demonstrating the greatest clinical improvement long-term, despite no group or strata differences at preceding time points. Response and remission outcomes did not differ by treatment group or hsCRP strata at any time point. Changes in hsCRP between baseline and week 35 and Tumour Necrosis Factor-α (TNF-α) concentrations between baseline and week 6 and baseline and week 35 were statistically significantly associated with MADRS scores observed at week 6 and week 35 respectively, with reducing TNF-α concentrations associated with reducing MADRS scores and vice versa in each case. A post-hoc stratification of the participant cohort by baseline TNF-α concentrations led to significant prediction by the derived strata on clinical response at weeks 6, 8 and 35, with participants with elevated baseline TNF-α less likely to achieve clinical response., Interpretation: The present analysis suggests for the first time a possible longer-term clinical benefit of celecoxib augmentation of vortioxetine in inflammation-associated MDD treatment. However, further research is needed to confirm the finding and to ascertain the reason for such a delayed effect. Furthermore, the trial suggests that TNF-α may have a stronger relationship with anti-inflammatory MDD treatment outcomes than hsCRP, and should be investigated further for potential predictive utility., Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p., (Copyright © 2024. Published by Elsevier Inc.)