Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations

Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Due to the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs in order to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability; (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation; (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse; and (4) post-marketing epidemiological studies

Appendectomy versus conservative treatment with antibiotics for patients with uncomplicated acute appendicitis: a propensity score–matched analysis of patient-centered outcomes (the ACTUAA prospective multicenter trial)

Purpose: The aim of this prospective multicenter study was to compare antibiotic therapy and appendectomy as treatment for patients with uncomplicated appendicitis confirmed by ultrasound and/or computed tomography. Methods: The study was conducted from January 2017 to January 2018. Data regarding all patients discharged from the participating centers with a diagnosis of uncomplicated appendicitis were collected prospectively. Results: Of the 318 patients enrolled in the study, 27.4% underwent antibiotic-first therapy, and 72.6% underwent appendectomy. The matched group was composed of 87 patients in both study arms. Of the 87 patients available of 1-year follow-up in the antibiotic-first group, 64 (73.6%) did not require appendectomy. The complication-free treatment success in the antibiotic-first group was 64.4%. A statistically significant higher complication-free treatment success was found in the appendectomy group: 81.8% in the pre-matching sample and 83.9% in the post-matching sample. Patients in the antibiotic-first group reported lower VAS scores compared to those treated with an appendectomy, both at discharge (2.0 ± 1.7 vs 3.6 ± 2.3) and at 30-day follow-up (0.3 ± 0.6 vs 2.1 ± 1.7). The mean of the days of absence from work was higher in the appendectomy group (β 0.63; 95% CI 0.08–1.18). Conclusion: Although laparoscopic appendectomy remains the gold standard of treatment for uncomplicated appendicitis, conservative treatment with antibiotics is a safe option in most cases. Approximately 65% of patients treated with antibiotics are symptom-free at 1 year, without increased risk of adverse events should symptoms recur, and better outcomes in terms of less pain and shorter period of absence from work compared to patients undergoing an appendectomy. Trial registration: Clinicaltrials.gov identifier (NCT number): NCT03080103

Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations

Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Due to the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs in order to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability; (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation; (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse; and (4) post-marketing epidemiological studies

Attentional bias for prescription opioid cues among opioid dependent chronic pain patients

Recurrent use of prescription opioid analgesics by chronic pain patients may result in opioid dependence, which involves implicit neurocognitive operations that organize and impel craving states and compulsive drug taking behavior. Prior studies have identified an attentional bias (AB) towards heroin among heroin dependent individuals. The aim of this study was to determine whether opioid-dependent chronic pain patients exhibit an AB towards prescription opioidrelated cues. Opioid-dependent chronic pain patients (n = 32) and a comparison group of non-dependent opioid users with chronic pain (n = 33) completed a dot probe task designed to measure opioid AB. Participants also rated their opioid craving and self-reported arousal associated with opioid-related and neutral images, pain severity, and relief from pain treatments. Repeated-measures ANOVA revealed a significant group (opioid-dependent vs. non-dependent opioid user) × presentation duration (200 ms. vs. 2000 ms.) interaction, such that opioid-dependent individuals evidenced a significant AB towards opioid cues presented for 200 ms but not for cues presented for 2000 ms, whereas non-dependent opioid users did not exhibit a significant mean AB at either stimulus duration. Among opioid-dependent individuals, 200 ms opioid AB was significantly associated with opioid craving, while among non-dependent opioid users, 200 ms opioid AB was significantly associated with relief from pain treatments. Furthermore, dependent and non-dependent opioid users experienced opioid cues as significantly more arousing than neutral cues. Opioid dependence among chronic pain patients appears to involve an automatic AB towards opioid-related cues. When coupled with chronic pain, attentional fixation on opioid cues may promote compulsive drug use and addictive behavior