The effects of low-dose morphine on sleep and breathlessness in COPD: A randomized trial.

Background: Low-dose morphine may be prescribed to reduce chronic breathlessness in chronic obstructive pulmonary disease (COPD). Recent subjective findings suggest morphine may influence breathlessness through sleep-related mechanisms. However, concerns exist regarding opioid safety in COPD.

Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?

Aims: To examine the associations between and polymorphisms, plasma oxycodone and metabolite concentrations, and oxycodone response (dose, pain scores, and adverse effects) in people with pain from advanced cancer.

Patients & Methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects), and blood (pharmacokinetics, DNA). Negative binomial regression and logistic regression were used.

Influence of (rs4680) and (rs1799971) on Cancer Pain, Opioid Dose, and Adverse Effects.

The influence of pharmacogenomics on opioid response, particularly with (rs4680) and (rs1799971) variants, has been studied individually and in combination. However, most studies are in a noncancer context and not all their possible variant combinations have been examined. This study examined (rs4680) and (rs1799971), and their allele combinations, in advanced cancer to examine associations with pain scores, opioid dose, and adverse effects.

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy.

Methadone is a mu (μ) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of R- and S-enantiomers. R-methadone has 30-to 50-fold higher analgesic potency than S-methadone, and S-methadone has a greater adverse effect (prolongation) on the cardiac QTc interval.

Cognitive outcomes from the randomised, active-controlled Ketamine for Adult Depression Study (KADS).

Background: Due to its rapid antidepressant effect, ketamine has recently been clinically translated for people with treatment-resistant depression. However, its cognitive profile remains unclear, particularly with repeated and higher doses. In the present study, we report the cognitive results from a recent large multicentre randomised controlled trial, the Ketamine for Adult Depression Study (KADS).

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

Background: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

Aims: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.

Opioid Switch Dosing in Chronic Cancer Pain: A Prospective Longitudinal Study.

Opioid switching is common, however, conversion tables have limitations. Guidelines suggest postswitch dose reduction, yet, observations show opioid doses may increase postswitch. To document the opioid conversion factor postswitch in cancer, and whether pain and adverse effect outcomes differ between switched opioid groups.

The Study of Ketamine for Youth Depression (SKY-D): study protocol for a randomised controlled trial of low-dose ketamine for young people with major depressive disorder.

Background: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD).

Methods: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government's National Health and Medical Research Council (NHMRC).

Serum lidocaine (lignocaine) concentrations during prolonged perioperative infusion in patients undergoing breast cancer surgery: A secondary analysis of a randomised controlled trial.

Perioperative lidocaine (lignocaine) infusions are being employed with increasing frequency. The determinants of systemic lidocaine concentrations during prolonged administration are unclear. In the Long-term Outcomes after Lidocaine Infusions for PostOperative Pain (LOLIPOP) pilot trial, the impact of infusion duration and body size metrics on serum lidocaine concentrations was examined with regression models in 48 women undergoing breast cancer surgery.

Effectiveness of Opioid Switching in Advanced Cancer Pain: A Prospective Observational Cohort Study.

Opioid switching is a common practice of substituting one opioid for another to improve analgesia or adverse effects; however, it has limited evidence. This study aimed to examine the effectiveness of opioid switching in advanced cancer. This multi-center prospective cohort study recruited patients assessed to switch opioids (opioid switch group) or to continue ongoing opioid treatment (control group).

Identification and kinetics of microsomal and recombinant equine liver cytochrome P450 enzymes responsible for in vitro metabolism of omeprazole.

In humans, omeprazole is metabolised by cytochrome P450 (CYP450) CYP2C19 and CYP3A4 with differences in CYP2C19 genotypes leading to variable response to therapy. Despite a wide use of omeprazole in horses with evidence of variable therapeutic efficiency, information regarding enzymatic metabolism is not currently available. This study aims to describe the in vitro kinetics of omeprazole metabolism and determine which enzyme(s) are responsible for omeprazole metabolism in horses.

Horse Grimace Scale Does Not Detect Pain in Horses with Equine Gastric Ulcer Syndrome.

Equine gastric ulcer syndrome (EGUS) is a highly prevalent and presumptively painful condition, although the amount of pain horses might experience is currently unknown. The aims of this study were to determine if the Horse Grimace Scale (HGS) could identify pain behaviours in horses with and without EGUS and if severity would be positively associated with the HGS score. Horse grimace scale scores were assessed blindly using facial photographs by seven observers and involved evaluation of 6 facial action units as 0 (not present), 1 (moderately present) and 2 (obviously present).

The incidence, impact, and risk factors for moderate to severe persistent pain after breast cancer surgery: a prospective cohort study.

Background: Few Australasian studies have evaluated persistent pain after breast cancer surgery.

Objective: To evaluate the incidence, impact, and risk factors of moderate to severe persistent pain after breast cancer surgery in a New Zealand cohort.

Design: Prospective cohort study.

Trajectories of Pain and Function Outcomes up to 5 to 8 Years Following Total Knee Arthroplasty.

Background: There appears to be substantial variability in outcomes > 2 years following total knee arthroplasty (TKA) that is masked by whole group analyses. The goal of the study was to identify trajectories of pain and function outcomes up to 5 to 8 years post-TKA and to identify baseline factors that are associated with different trajectories of recovery.

Methods: Baseline, 6-month, and 12-month pain and function data were collected in a previous study investigating predictors of outcome following primary TKA (n = 286), along with a variety of baseline predictor variables.

Establishing a Longitudinal Opioid Pharmacogenomic Registry for Cancer Patients: Feasibility and Acceptability.

Individual genetic variation can affect both pain expression and opioid response. Large cohort datasets are required to validate evidence influencing genomic factors in opioid response. This study examined the feasibility of establishing an opioid pharmacogenomics registry for cancer patients containing longitudinal matched clinical, symptom, pharmacological, and genomic data, with an feasibility target of 50 participants within 12 months.

Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by medication exposure. Regulatory agencies worldwide warn against the use of certain medications in persons with G6PD deficiency, but in many cases, this information is conflicting, and the clinical evidence is sparse. This guideline provides information on using G6PD genotype as part of the diagnosis of G6PD deficiency and classifies medications that have been previously implicated as unsafe in individuals with G6PD deficiency by one or more sources.

The Role of Pharmacogenomics in Opioid Prescribing.

Pharmacogenomics is increasingly important to guide objective, safe, and effective individualised prescribing. Personalised prescribing has revolutionised treatments in the past decade, allowing clinicians to maximise drug efficacy and minimise adverse effects based on a person's genetic profile. Opioids, the gold standard for cancer pain relief, are among the commonest medications prescribed in palliative care practice.

Population Pharmacokinetics and Pharmacodynamics of the Therapeutic and Adverse Effects of Ketamine in Patients With Treatment-Refractory Depression.

We aimed to develop population pharmacokinetic/pharmacodynamic (PK/PD) models that can effectively describe ketamine and norketamine PK/PD relationships for Montgomery-Åsberg Depression Rating Scale (MADRS) scores, blood pressure (BP), and heart rate (HR) following i.v., s.

A systematic literature review and meta-analysis of the effect of psilocybin and methylenedioxymethamphetamine on mental, behavioural or developmental disorders.

Objectives: There is an increasing interest in combining psilocybin or methylenedioxymethamphetamine with psychological support in treating psychiatric disorders. Although there have been several recent systematic reviews, study and participant numbers have been limited, and the field is rapidly evolving with the publication of more studies. We therefore conducted a systematic review of PubMed, MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL for randomised controlled trials of methylenedioxymethamphetamine and psilocybin with either inactive or active controls.

Toll-like receptors change morphine-induced antinociception, tolerance and dependence: Studies using male and female TLR and signalling gene KO mice.

Toll-like receptors (TLR) have been proposed as a site of action that alters opioid pharmacodynamics. However, a comprehensive assessment of acute opioid antinociception, tolerance and withdrawal behaviours in genetic null mutant strains with altered innate immune signalling has not been performed. Nor has the impact of genetic deletion of TLR2/4 on high-affinity opioid receptor binding.