Cannabis combined with oxycodone for pain relief in fibromyalgia pain: a randomized clinical self-titration trial with focus on adverse events.

Objectives: We determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia.

Methods: In this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.

Opioid prescribing in the Netherlands during the COVID-19 pandemic: a national register-based study.

Objectives: The COVID-19 pandemic and related lockdown measures disrupted global healthcare provision, including opioid prescribing. In North America, opioid sales declined while opioid-related deaths increased. In Europe, the effect of the pandemic on prescribing is not yet known.

Opioid Overdose: Limitations in Naloxone Reversal of Respiratory Depression and Prevention of Cardiac Arrest.

Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the only available treatment for reversing the negative effects of opioids, including respiratory depression. However, the effectiveness of naloxone, particularly after an opioid overdose, varies depending on the pharmacokinetics and the pharmacodynamics of the opioid that was overdosed.

What Changes Have Occurred in Opioid Prescriptions and the Prescribers of Opioids Before TKA and THA? A Large National Registry Study.

Background: Opioid use before TKA or THA is linked to a higher risk of revision surgery and less functional improvement. In Western countries, the frequency of preoperative opioid use has varied, and robust information on temporal changes in opioid prescriptions over time (in the months before surgery as well as annual changes) and among prescribers is necessary to pinpoint opportunities to improve on low-value care patterns, and when they are recognized, to target physician populations for intervention strategies.

Questions/purposes: (1) What proportion of patients undergoing arthroplasties receive an opioid prescription in the year before TKA or THA, and what were the preoperative opioid prescription rates over time between 2013 and 2018? (2) Does the preoperative prescription rate vary between 12 and 10 months and between 3 and 1 months in the year before TKA or THA, and did it change between 2013 and 2018? (3) Which medical professionals were the main prescribers of preoperative opioids 1 year before TKA or THA?

Methods: This was a large-database study drawn from longitudinally maintained national registry sources in the Netherlands.

Out-of-hospital opioid prescriptions after knee and hip arthroplasty: prescribers and the first prescribed opioid.

Background: We determined the first prescribed opioid and the prescribers of opioids after knee and hip arthroplasty (KA/HA) between 2013 and 2018 in the Netherlands. We also evaluated whether the first prescribed opioid dose was associated with the total dispensed dose and long-term opioid use in the first postoperative year.

Methods: The Dutch Foundation for Pharmaceutical Statistics was linked to the Dutch Arthroplasty Register.

Opioid epidemic: lessons learned and updated recommendations for misuse involving prescription versus non-prescription opioids.

Introduction: In the past decades, the opioid crisis has heavily impacted parts of the US society and has been followed by an increase in the use of opioids worldwide. It is of paramount importance that we explore the origins of the US opioid epidemic to develop best practices to tackle the rising tide of opioid overdoses.

Areas Covered: In this expert review, we discuss opioid (over)prescription, change in perception of pain, and false advertisement of opioid safety as the leading causes of the US opioid epidemic.

Opioid prescribing patterns after arthroplasty of the knee and hip: a Dutch nationwide cohort study from 2013 to 2018.

Background And Purpose: Numbers on opioid prescriptions over time in arthroplasty patients are currently lacking. Therefore we determined the annual opioid prescribing rate in patients who received a hip/knee arthroplasty (HA/KA) between 2013 and 2018.

Patients And Methods: The Dutch Foundation for Pharmaceutical Statistics, which provides national coverage of medication prescriptions, was linked to the Dutch Arthroplasty Register, which provides arthroplasty procedures.

Association between prescription opioid use and unplanned intensive care unit admission and mortality in the adult population of the Netherlands: a registry study.

Background: Opioid overdoses are increasing in the Netherlands, and there may be other harms associated with prescription opioid use. We investigated the relationship between prescription opioid use and unplanned ICU admission and death.

Methods: This is an analysis of linked government registries of the adult Dutch population (age ≥18 years) alive on January 1, 2018.

Comparison of Two Different Analgesic Prescription Strategies and Healthcare Systems: Slovenia vs. the Netherlands.

Prescribing practice of pain medication is changing in the Netherlands; opioids are used more often instead of nonsteroidal anti-inflammatory drugs (NSAIDs), therefore we aimed to compare the use of pain medication with Slovenia which has stringent prescribing rules for strong opioids. We conducted a cohort study into national prescription databases of the Netherlands and Slovenia covering pharmacy claims between January 1, 2013 and December 31, 2019. In the analysis about 17 million Dutch and 2 million Slovenian residents were included.

Risk of drug-related upper gastrointestinal bleeding in the total population of the Netherlands: a time-trend analysis.

Objective: Many prescribed and over-the-counter medications, for example, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with upper gastrointestinal bleeding (UGIB). Recently, a decrease in prescribing of NSAIDs was observed in the Netherlands, but whether a similar decreasing trend could be observed in the incidence of severe UGIB (either fatal or requiring hospitalisation), contingent on medication prescription, is unknown.

Design: We conducted a cohort study using Dutch national statistics on pharmacy claims, hospitalisation and mortality between 2013 and 2018.

Efficacy of ketamine in relieving neuropathic pain: a systematic review and meta-analysis of animal studies.

In humans, proof of long-term efficacy of ketamine treatment in neuropathic pain is lacking. To improve our understanding of ketamine behavior under various administration conditions, we performed a systematic review and meta-analyses of controlled studies on the efficacy of ketamine in mice and rats with a disease model of nerve injury on relief of allodynia. Searches in PubMed and EMBASE identified 31 unique studies.

Combining opioids and benzodiazepines: effects on mortality and severe adverse respiratory events.

Opioids and benzodiazepines are increasingly used alone or in combination. However, the combined use of these agents increases the risk for potentially lethal respiratory depression. This review summarizes current evidence on the effects of the combined use of opioids and benzodiazepines on mortality and severe respiratory adverse events.

Opioid Prescription Patterns and Risk Factors Associated With Opioid Use in the Netherlands.

Importance: An increase in opioid prescription has been observed in the Netherlands. It is vital to understand this increase and to identify risk factors for opioid prescription to ensure that health interventions remain appropriately targeted.

Objectives: To determine the prevalence of opioid prescriptions and adverse events associated with opioids, and to identify risk factors associated with opioid prescription in the Dutch population.

Does nociception monitor-guided anesthesia affect opioid consumption? A systematic review of randomized controlled trials.

Monitors that estimate nociception during anesthesia may be used to guide opioid and other analgesics administration to optimize anesthesia care and possibly outcome. We reviewed the literature to evaluate current evidence of the effect of nociception-guided management over standard anesthesia practice during surgery. A systematic review of the literature on the effect of nociception monitoring on anesthesia practice was conducted.

Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women.

What is the central question of this study? Does a clinically relevant intravenous dose of erythropoeitin affect the hypoxic ventilatory response and/or hypoxic pulmonary vasoconstriction in healthy humans? What is the main finding and its importance? Erythropoeitin does not influence the ventilatory and pulmonary vascular responses to acute hypoxia in men or women. Sustained and chronic hypoxia lead to an increase in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical i.

A retrospective study on persistent pain after childbirth in the Netherlands.

Reported prevalence rates of persistent postpartum pain (PPP) range from less than 1% to almost 20%. The aim of this study was to examine the prevalence of PPP in a Dutch cohort and to evaluate a possible causal role for specific risk factors on the development of chronic pain after childbirth. A questionnaire was sent to 960 postpartum women approximately 2 years after delivery.

Opioid chronopharmacology: influence of timing of infusion on fentanyl's analgesic efficacy in healthy human volunteers.

Chronopharmacology studies the effect of the timing of drug administration on drug effect. Here, we measured the influence of 4 timing moments on fentanyl-induced antinociception in healthy volunteers. Eight subjects received 2.

Arterial and venous pharmacokinetics of morphine-6-glucuronide and impact of sample site on pharmacodynamic parameter estimates.

Background: In pharmacokinetic-pharmacodynamic modeling studies, venous plasma samples are sometimes used to derive pharmacodynamic model parameters. In the current study the extent of arteriovenous concentration differences of morphine-6-glucuronide (M6G) was quantified. We used simulation studies to estimate possible biases in pharmacodynamic model parameters when linking venous versus arterial concentrations to effect.

Naloxone reversal of morphine- and morphine-6-glucuronide-induced respiratory depression in healthy volunteers: a mechanism-based pharmacokinetic-pharmacodynamic modeling study.

Background: Opioid-induced respiratory depression is antagonized effectively by the competitive opioid receptor antagonist naloxone. However, to fully understand the complex opioid agonist-antagonist interaction, the effects of various naloxone doses on morphine and morphine-6-glucuronide (M6G)-induced respiratory depression were studied in healthy volunteers.

Methods: Twenty-four subjects received 0.

Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis.

In this study, we investigated possible separate effects of H+ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic - normoxic) ventilation over (hypoxic - normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic - normoxic) ventilation over (logPa(O2) hypoxia - logPa(O2) normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis.