PANSAID - PAracetamol and NSAID in combination:study protocol for a randomised trial

BACKGROUND: Effective postoperative pain management is essential for the rehabilitation of the surgical patient. No ‘gold standard’ exists after total hip arthroplasty (THA) and combinations of different nonopioid medications are used with virtually no evidence for additional analgesic efficacy compared to monotherapy. The objective of this trial is to investigate the analgesic effects and safety of paracetamol and ibuprofen alone and in combination in different dosages after THA. METHODS: PANSAID is a placebo-controlled, parallel four-group, multicentre trial with centralised computer-generated allocation sequence and allocation concealment and with varying block size and stratification by site. Blinding of assessor, investigator, caregivers, patients and statisticians. Patients are randomised to four groups: (A) paracetamol 1 g × 4 and ibuprofen 400 mg × 4, (B) paracetamol 1 g × 4 and placebo, (C) placebo and ibuprofen 400 mg × 4 and (D) paracetamol 0.5 g × 4 and ibuprofen 200 mg. The two co-primary outcomes are 24-h consumption of morphine and number of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and number of patients with one or more adverse events within 24 h postoperatively. Inclusion criteria are patients scheduled for unilateral, primary THA; age above 18 years; ASA status 1–3; BMI >18 and <40 kg/m(2); women must not be pregnant; and provision of informed consent. Exclusion criteria are patients who cannot cooperate with the trial; participation in another trial; patients who cannot understand/speak Danish; daily use of strong opioids; allergy against trial medication; contraindications against ibuprofen; alcohol and/or drug abuse. A total of 556 eligible patients are needed to detect a difference of 10 mg morphine i.v. the first 24 h postoperatively with a standard deviation of 20 mg and a family wise type 1 error rate of 0.025 (two-sided) and a type 2 error rate of 0.10 for the six possible comparisons of the four intervention groups. DISCUSSION: We started recruiting patients in December 2015 and expect to finish in September 2017. Data analysis will be from September 2017 to October 2017 and manuscript submission ultimo 2017. TRIAL REGISTRATION: EudraCT: 2015-002239-16 (12/8-15); ClinicalTrials.gov: NCT02571361. Registered on 7 October 2015. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1749-7) contains supplementary material, which is available to authorized users

Adaptations in mitochondrial enzymatic activity occurs independent of genomic dosage in response to aerobic exercise training and deconditioning in human skeletal muscle

Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p &lt; 0.01). Citrate synthase and mitochondrial respiratory chain complex I&ndash;IV activities were increased by 51% and 46&ndash;61%, respectively, in the trained leg (p &lt; 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I&ndash;IV activities by 29&ndash;36% (p &lt; 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA

Postoperative pain treatment after lumbar discectomy. A protocol for a systematic review with meta-analysis and trial sequential analysis

Background: Patients undergoing lumbar discectomy usually suffer from moderate to severe pain during the postoperative period. Multimodal, or balanced analgesia, is the leading treatment principle for managing postoperative pain. The rationale is to achieve optimal pain treatment through additive or synergistic effects of several non-opioid analgesics, and thereby, reducing the need for postoperative opioids, facilitating early mobilization and functional rehabilitation. For discectomy surgery, evidence of both the benefit and harm of different analgesic interventions is unclear. Objectives: This systematic review aims to investigate the benefits and harms of analgesic interventions in adult patients after lumbar discectomy. Methods: This protocol for a systematic review is written according to The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search The Cochrane Library's CENTRAL, PubMed, EMBASE, and ClinicalTrails.gov for published and ongoing trials. All randomized clinical trials assessing the postoperative analgesics effect of an intervention with a control or no-intervention group undergoing lumbar discectomy will be included. Two authors will independently screen trials for inclusion using Covidence, extract data and assess the risk of bias using Cochrane's risk-of-bias 2 tool. We will analyse the data using Review Manager and Trial Sequential Analysis. Meta-analysis will be performed according to the Cochrane guidelines. We will present our primary findings in a ‘summary of findings’ table and evaluate the overall certainty of evidence using the GRADE approach. Discussion: This systematic review will assess the benefits and harms of analgesic interventions after lumbar discectomy and have the potential to improve best practices and advance research