Analgesic effect of the ultrasound-guided thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy: a randomized controlled trial.

BACKGROUND: Paravertebral block has similar effect as epidural anesthesia, and has good somatic and visceral analgesic effect. Paravertebral block is widely used in thoracic surgery, but rarely used in abdominal surgery. AIMS: This study aimed to evaluate the analgesic effect of thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy. METHODS: One hundred patients undergoing elective robot-assisted laparoscopic nephrectomy were included in this study. Based on whether the thoracolumbar paravertebral block was performed, the patients were randomly divided into the thoracolumbar paravertebral block combined with general anesthesia group (TL-PVB group) and simple general anesthesia group (NO-PVB group). Oxycodone was administered for patient-controlled intravenous analgesia (PCIA). The primary outcomes included the amount of remifentanil used during surgery, the amount of oxycodone used in 24 and 48 h after surgery. Secondary outcomes included the changes of heart rate (HR) and mean arterial pressure (MAP), time for the first analgesia administration, visual analog score (VAS) of pain during rest and movement, and time of postoperative recovery. RESULTS: Compared to the NO-PVB group, the amount of remifentanil used during surgery in patients with TL-PVB group was significantly reduced (1.78 ± 0.37 mg vs. 3.09 ± 0.48 mg, p < 0.001), the amount of oxycodone used 24 h after surgery was significantly reduced (8.70 ± 1.70 mg vs. 13.79 ± 2.74 mg, p < 0.001), and the amount of oxycodone used 48 h after surgery was remarkably reduced (21.83 ± 4.28 mg vs. 27.27 ± 4.76 mg, p < 0.001). There were significant differences in the changes of HR and MAP between the two groups (p < 0.001). The first analgesic requirement time of TL-PVB group was significantly longer than that of NO-PVB group (468.56 ± 169.60 min vs. 113.48 ± 37.26 min, p < 0.001). The postoperative VAS during rest and movement of TL-PVB group were significantly lower than that of NO-PVB group (p < 0.01). Compared with NO-PVB group, patients in TL-PVB group needed shorter time to awaken from anesthesia, leave the operating room, anal exhaust, get out of bed, and had shorter length of postoperative hospital stay (p < 0.001). The incidence of postoperative adverse reactions were lower in the TL-PVB group than that in the NO-PVB group (p < 0.05). CONCLUSIONS: Ultrasound-guided thoracolumbar paravertebral block significantly reduces intraoperative and postoperative opioid consumption, and provides better analgesia in patients undergoing robot-assisted laparoscopic nephrectomy, which is a recommendable combined anesthesia technique. TRIAL REGISTRATION: ChiCTR2200061326, 21/06/2022.

Opioid prescriber responsibility: A Danish drug utilization study.

AIMS: We describe the distribution of prescribers responsible for opioid initiation and maintenance (general practice, hospital prescribers and other prescribers) in Denmark. METHODS: We leveraged data on opioid fills from a 20% sample of all Danes alive during 2000-2021. RESULTS: Overall, general practitioners were responsible for most treatment initiation (74% during 2000-2021) and maintenance treatment (92%). However, while hospital prescribers initiated ≈20% of treatments during 2001-2012, this increased to 35% in 2021. Similarly, hospital prescriber's share of maintenance treatment increased from 5.9% during 2000-2012 to 13% in 2021. This change was particularly pronounced for morphine initiation (48% hospital prescribers in 2021 up from 38% during 2000-2010) and oxycodone initiation (78% up from 41%). Regarding choice of opioids, codeine use dropped markedly, in particular among hospital prescribers. Tramadol was consistently the most common first choice opioid in general practice (33% in 2021), whereas its use among hospital prescribers decreased (54% during 2000-2015 to 15% in 2021). Conversely, the proportion of treatment initiation by hospital prescribers composed of morphine and oxycodone increased to 38% and 42% in 2021, respectively. CONCLUSIONS: General practice prescribes most opioids; however, hospital prescribers are increasingly responsible for opioid prescribing, in particular initiation of morphine and oxycodone.

Safety and Efficacy of Liposomal Bupivacaine Supraclavicular Nerve Blocks in Open Treatment of Distal Radius Fractures: A Perioperative Pain Management Protocol.

INTRODUCTION: Distal radius fractures (DRFs) are common fractures requiring surgical fixation. The literature varies regarding opioid prescribing habits, opioid consumption, and postoperative pain scores. We hypothesized that the preoperative administration of a liposomal bupivacaine (LB) supraclavicular nerve block would be safe and effective in controlling postoperative pain. METHODS: A standardized pain management protocol was implemented at a single institution from July 2021 to March 2022 for patients undergoing open reduction internal fixation of DRF. Protocol elements included a preoperative LB supraclavicular nerve block and a multimodal postoperative pain regimen. Primary clinical outcomes included postoperative pain scores and number of opioid tablets consumed. RESULTS: Twenty patients underwent a newly implemented protocol. The average age was 56 years. Mean number of oxycodone 5-mg tablets consumed was 4.1 (median, 2.5), and mean visual analog scale pain score at first postoperative appointment was 2.8. There were no incidences of missed acute carpal tunnel postoperatively. When compared with an institutional historical control (n = 189), number of opioid pills prescribed was reduced by 60% (21.4 vs 8.6 tablets, P < 0.0001), and no patients had unscheduled health care contact because of uncontrolled pain (22% vs 0%, P < 0.016). CONCLUSIONS: Liposomal bupivacaine supraclavicular nerve blocks are safe and effective in the treatment of postoperative pain after open reduction internal fixation of DRF. Patients consumed <5 oxycodone tablets on average, which is less than many recommend prescribed quantities (>20-30 tablets). Patients had low pain scores (2.8/10) at the first postoperative follow-up. To our knowledge, this is the first study demonstrating the utility of LB in this clinical setting.

Effect of joint immobilization using extension splint immediately after total knee arthroplasty on post-operative knee function and pain: a randomized clinical trial.

PURPOSE: Investigate the effect of semirigid extension bracing after total knee arthroplasty (TKA) on articular pain and function. METHODS: The present randomized clinical trial included 72 patients undergoing unilateral primary TKA. Patients in the case group received eight days of post-operative semirigid extension-locked knee bracing, whereas controls did not. The outcomes assessed preoperatively and on the first, ninth, 30th day, and one year post-operatively included the knee society score (KSS), functional KSS (FKSS), VAS pain score, amount of postoperative opiate painkiller usage (tablet oxycodone 5mg), and knee ROM. RESULTS: The case group had a significantly lower flexion ROM on postoperative day nine compared to the control group (95.3° vs. 100.8°, p=0.03), while it became significantly higher 1 month (114.1° vs. 104.7°, p=0.03) and one year post-operative (128.0° vs. 120.5°, p=0.002). Also, FKSS was significantly higher in the case group than in the controls in the one month post-operative assessment (37.0 vs. 32.6, p=0.009) but not in the one year post-operative assessment. The case group patients had a significantly lower pain than the controls on days one (5.8 vs. 7.2, p=0.02) and nine post-operative (4.1 vs. 5.2, p=0.048), but not at later assessments. The amount of one month post-operative opium (oxycodone) consumption was significantly lower in the brace group (12.4 vs. 14.1 tablets, p=0.03). The KSS were not significantly different between the groups after the surgery. CONCLUSION: Extension-locked splinting immediately after TKA is a noninvasive, non-pharmacological, and inexpensive intervention with possible promising effects on knee ROM, short-term functional improvement, and acute post-operative pain management.

Effects of anaesthesia method and tourniquet use on recovery following total knee arthroplasty: a randomised controlled study.

BACKGROUND: We investigated the effects of spinal and general anaesthesia and surgical tourniquet on acute pain and early recovery after total knee arthroplasty (TKA). METHODS: Patients (n=413) were randomised to four parallel groups: spinal anaesthesia with or without tourniquet, and general anaesthesia with or without tourniquet. The primary outcome was patient-controlled i.v. oxycodone consumption over 24 postoperative hours. RESULTS: Results from 395 subjects were analysed. Median i.v. oxycodone consumption did not differ between the four groups (spinal anaesthesia without [36.6 mg] and with tourniquet [38.0 mg], general anaesthesia without [42.3 mg] and with tourniquet [42.5 mg], P=0.42), between spinal (37.7 mg) and general anaesthesia (42.5 mg) groups (median difference -3.1, 95% confidence interval [CI] -7.4 to 1.2, P=0.15) and between tourniquet and no-tourniquet groups (40.0 vs 40.0 mg, median difference -0.8, CI -5.1 to 3.5, P=0.72). Vomiting incidence was higher with spinal than with general anaesthesia (21% [42/200] vs 13% [25/194], CI 1.05 to 3.1, P=0.034). The mean haemoglobin decrease was greater without than with tourniquet (-3.0 vs -2.5 g dl-1, mean difference -0.48, CI -0.65 to -0.32, P<0.001). No differences were observed in pain, pain management, incidences of blood transfusions, in-hospital complications, or length of hospital stay. CONCLUSIONS: For TKA, spinal and general anaesthesia with or without tourniquet did not differ in 24-h postoperative opioid consumption, pain management, blood transfusions, in-hospital complications, and length of hospital stay. Vomiting incidence was higher in the spinal than in the general anaesthesia group. Tourniquet use caused smaller decreases in haemoglobin levels. CLINICAL TRIAL REGISTRATION: EudraCT 2016-002035-15.

Effects of oxycodone applied for patient-controlled analgesia on postoperative cognitive function in elderly patients undergoing total hip arthroplasty: a randomized controlled clinical trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after orthopedic surgery, which is not conducive to the prognosis of the elderly. AIMS: We performed this study to investigate the effects of oxycodone applied for patient-controlled intravenous analgesia (PCIA) on postoperative cognitive function in elderly patients after total hip arthroplasty (THA). METHODS: Ninety-nine participants were enrolled and allocated into two groups: oxycodone group (group O) and sufentanil group (group S). The primary outcome was the incidence of POCD, diagnosed according to the changes in the Mini-mental status examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The secondary outcomes included the plasma levels of S-100B protein and neuron-specific enolase (NSE), the amount of postoperative analgesic consumption and the incidence of adverse reactions. RESULTS: The incidence of POCD was significantly lower in patients receiving oxycodone up to the 3rd postoperative day (POD, 1st POD 27.3% vs. 51.1%, P = 0.021; 3rd POD 20.5% vs. 40.0%, P = 0.045), as compared to patients receiving sufentanil. The MMSE and MoCA scores of both groups decreased to varying degrees. However, compared with group S, the MMSE scores at 1st POD, 3rd POD, 5th POD and 7st POD in group O were higher than that in group S, while MoCA scores at 1st POD, 3rd POD and 5th POD in group O were higher. Compared with group S, the plasma levels of S-100B protein in group O at 4 h, 8 h, 12 h post-surgery were lower. While the plasma levels of NSE in group O at 4 h, 8 h, 12 h, 24 h post-surgery were lower. Number of PCIA boluses and consumption of analgesic drug during the first two POD were similar between two groups. However, postoperative incidence of nausea, vomiting and pruritus was significantly lower in patients receiving oxycodone. CONCLUSION: Oxycodone applied for PCIA in elderly patients after THA could reduce the incidence of POCD, improve postoperative cognitive function and decrease the adverse reactions.

A sustainable method to reduce postoperative oxycodone discharge prescribing in a metropolitan tertiary referral hospital.

The primary objective of this quality improvement project was to measure and reduce the number of oxycodone immediate-release tablets dispensed to overnight stay surgical patients at discharge. The secondary objective was to reduce the proportion of inappropriate oxycodone immediate-release prescriptions at discharge. Interrupted time series analysis was performed in four surgical wards of St Vincent's Public Hospital, Sydney. The baseline period was from January 2005 to August 2013. Interventions and follow-up occurred until July 2017. Baseline audit of oxycodone immediate-release tablet numbers showed prescribing increased significantly with a monthly linear trend of 1.8 (95%CI = 1.4-2.3; p = 0.001) tablets/100 surgical admissions from January 2005 to August 2013. Four sequential interventions produced no significant change in the primary objective. At the end of the first month of a fifth intervention, comprising audit-feedback plus individual academic detailing, the average number of oxycodone tablets decreased by 77 (95%CI 39-115) tablets/100 surgical cases, and the postintervention linear trend was a monthly reduction of 3.2 (coefficient -3.2 (95%CI -4.5 to -1.8); p = 0.001) tablets/100 surgical admissions. Baseline audit showed 27% of oxycodone prescriptions to be inappropriate. Following our intervention, this dropped to 17% (p = 0.048), and then to 10% (p = 0.002) after 3 years.

Efficacy and Safety of Oxycodone Injection for Relieving Cancer Pain: A Study in Japan Consisting of Two Open Trials for Intravenous and Subcutaneous Administration.

Pure oxycodone injection became increasingly necessary after oral oxycodone was launched in Japan in 2003. However, trials clarifying the efficacy and safety of injection are rare. Therefore, a multicenter open study on injection was designed and carried out in 2010, resulting in the launch of injection therapy in 2012. As published domestic case reports on efficacy already show widespread prescription, this study aimed to provide useful information for cancer pain relief in Japan and other countries. Our oxycodone injection study consisted of two trials, one of intravenous (S#9131) and the other of subcutaneous (S#9132) administration. The minimum required number of enrolled patients suffering cancer pain was determined to be 70 in S#9131 and 20 in S#9132. These studies had the same dose-titration protocol as the main endpoint, i.e., pain relief rate (PRR) defined as the rate of achieving adequate pain control (APC), as in prior oral oxycodone trials in Japan. In S#9131, PRR was 81.4% (95% confidence interval: 70.3-89.7%), therefore, the null hypothesis of PRR<70% was rejected using the binominal one-sided test (p=0.0217). In S#9132, PRR was 73.7% also surpassing 70%. Safety was also assessed in the same way as in prior trials. The majority of adverse effects were moderate or mild and recovered with no sequelae. As shown above, the injection was considered to be effective and safe in cancer pain treatment. The details of these trials, particularly the dose-titration protocol for achieving APC and route switching information, are expected to enhance injection convenience for prescribers.

The Opioid Crisis and the Orthopedic Surgeon.

Opioid use and abuse has become a national crisis in the United States. Many opioid abusers become addicted through an initial course of legal, physician-prescribed medications. Consequently, there has been increased pressure on medical care providers to be better stewards of these medications. In orthopedic surgery and total joint arthroplasty, pain control after surgery is critical for restoring mobility and maintaining patient satisfaction in the early postoperative period. Before the opioid misuse epidemic, orthopedic surgeons were frequently influenced to "treat pain with pain medications." Long-acting opioids, such as OxyContin were used commonly. In the past decade, there has been a paradigm shift in favor of multimodal pain control with limited opioid use. This review will discuss 4 major topics. First, we will describe the pressures on orthopedic surgeons to prescribe narcotic pain medications. We will then discuss the major and minor complications and side effects associated with these prescriptions. Second, we will review how these factors motivated the development of alternative pain management strategies and a multimodal approach. Third, we will look at perioperative interventions that can reduce postoperative opioid consumption, including wound injections and peripheral nerve blocks, which have shown superb clinical results. Finally, we will recommend an evidence-based program that avoids parenteral narcotics and facilitates rapid discharge home without readmissions for pain-related complaints.

Aprepitant and fosaprepitant drug interactions: a systematic review.

AIMS: Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant. METHODS: We systematically reviewed the literature to September 11, 2016, to identify articles evaluating drug interactions involving aprepitant/fosaprepitant. The clinical significance of each reported pharmacokinetic drug interaction was evaluated based on the United States Food and Drug Administration guidance document on conducting drug interaction studies. The probability of an adverse event reported in case reports being due to a drug interaction with aprepitant/fosaprepitant was determined using the Drug Interaction Probability Scale. RESULTS: A total of 4377 publications were identified. Of these, 64 met inclusion eligibility criteria: 34 described pharmacokinetic drug interactions and 30 described adverse events ascribed to a drug interaction. Clinically significant pharmacokinetic interactions between aprepitant/fosaprepitant and bosutinib PO, cabazitaxel IV, cyclophosphamide IV, dexamethasone PO, methylprednisolone IV, midazolam PO/IV, oxycodone PO and tolbutamide PO were identified, as were adverse events resulting from an interaction between aprepitant/fosaprepitant and alcohol, anthracyclines, ifosfamide, oxycodone, quetiapine, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and warfarin. CONCLUSIONS: The potential for a drug interaction with aprepitant and fosaprepitant should be considered when selecting antiemetic therapy.

Premedication with fast-acting oxycodone hydrochloride hydrate effectively reduced oxaliplatin-induced severe vascular pain.

Oxaliplatin is a platinum-based chemotherapeutic agent that holds a prominent position in the treatment of colorectal and gastric cancers. However, severe oxaliplatin-related vascular pain can be problematic for patients. Here we describe seven patients who experienced severe vascular pain caused by oxaliplatin administration. All seven patients were treated with capecitabine and oxaliplatin or capecitabine plus oxaliplatin with bevacizumab as an adjuvant or a treatment for recurrent colorectal cancer, respectively. Patients experienced intolerable vascular pain during oxaliplatin administration, which continued for several days. Moreover, vascular pain also induced insomnia and appetite loss in all patients. We recommended implantation of a central venous (CV) port to the patients; however, all patients declined this treatment. In addition, various known countermeasures were taken, but were ineffective. Therefore, patients were orally administered oxycodone hydrochloride hydrate (Oxinorm®) 45 min prior to oxaliplatin administration. This pretreatment successfully reduced vascular pain and improved subsequent chemotherapy. Oxinorm® is a fast-acting opioid that can be an effective and practical option for severe vascular pain induced by oxaliplatin. The present report is the first description that emphasizes the usefulness of Oxinorm® to overcome the vascular pain induced by administration of oxaliplatin via a peripheral vein.

[Outcomes of an Independent Clinical Study to Compare Branded and Generic Formulations of Sustained-Release Oxycodone].

To evaluate the potential for the adoption of a generic formulation of sustained-release oxycodone(Oxycodone SR Capsules), an independent clinical study was planned to accurately evaluate the efficacy and safety during a 9-day period. After a 3-day pretreatment period, the generic formulation was administered to patients with progressive cancer, who had been treated with a branded formulation(OxyContin®Tablets)of the drug for 5 days at the same dose. This was followed by a 1- day observation period. Drug administration to 3 patients with pulmonary cancer achieved the primary(dose, pain level, and adverse drug reactions)and secondary(rescue dose frequency and quality of life)endpoints, as well as safety goals. The merits of adopting a different dosage form were also noted. Independent data collection using an appropriate evaluation method consequently promoted the understanding of generic opioids in the clinical setting.

Functional Outcomes of Patients Treated with Intensive Medications for Bowel and Pain Control for Low-Lying Rectal Cancer Who Received Preoperative Chemoradiotherapy.

PURPOSE: The aim of this study was to assess the functional outcomes of patients treated with intensive medications for bowel and pain control for low-lying rectal cancer who received preoperative chemoradiotherapy (CRT). METHODS: The inclusion criterion was sphincter-preserving surgery following CRT for T3 middle and low rectal cancer. Postoperative defecation control was conducted using calcium polycarbophil and loperamide, and anal pain control was conducted using oxycodone hydrochloride hydrate. The functional outcomes were determined by an annual questionnaire after stoma closure. RESULTS: Of 64 patients evaluated, 33 were reconstructed using the double stapling technique (DST) and 31 were reconstructed using the intersphincteric resection (ISR) technique. The median Visual Analogue Scale at ISR was improved from 7 to 1.5 at 1 year after surgery. The median Wexner scores were 6.0, 6.0, 5.0 and 5.0 for DST and 14.5, 12.0, 10.0 and 8.0 for ISR for the first 4 years, respectively. The only independent predictor of a poor bowel function (Wexner score >10) according to a multivariate analyses was pelvic infection (OR 3.994, 95% CI 1.235-13.52, p = 0.021), while ISR was not a predictor. CONCLUSIONS: Anal pain following ISR can be controlled with oxycodone hydrochloride hydrate therapy. ISR is feasible following CRT for low-lying rectal cancer.

[Random clinical study about application value of oxycodone in radiofrequency ablation of hepatocellular carcinoma].

Objective: To evaluate the clinical effect and safety of oxycodone hydrochloride in the anesthesia for percutaneous radiofrequency ablation (PRFA) in hepatocellular carcinoma. Methods: Between March and December 2015, 60 cases of hepatocellular carcinoma patients undergoing percutaneous radiofrequency ablation surgery in Peking University Cancer Hospital were randomly divided into three groups: oxycodone group (group Q), fentanyl group (group F) and dezocine group (group D), 20 cases in each group. Respectively intravenously injection oxycodone 0.1 mg/kg, fentanyl 0.001 mg/kg, dezocine 0.1 mg/kg before surgery. After the surgeon completed puncture administer propofol to maintain anesthesia. Recorded mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) changes in each group at entrance, beginning of radiofrequency ablation (T1), radiofrequency ablation began after 10 minutes (T2), the end of the surgical and awake. Observe the analgesia effect, respiratory depression, nausea, vomit and other complications. Postoperative pain scores were recorded.Using ANOVA, repeated measure variance analysis, SNK test, χ2 test and other tests to evaluate the anesthetic effect indexes. Results: The observation completed in all patients. Patients of three groups had no significant differences in general information. No significant difference between MAP, HR and SpO2 at each time points among the three groups. At the T1 time point (group Q: (11.7±1.6)/min, group D: (12.1±1.7)/min, group F: (10.3±2.3)/min, F=5.068, P=0.009) and T2 time point (group Q: (11.9±1.3)/min, group D: (12.2±1.4)/min, group F: (10.7±1.3)/min, F=7.024, P=0.002), RR in group F were lower than in group Q and group D. Pain visual analogue scores after waking (group Q: 0.2±0.7, group D: 0.3±0.7, group F: 1.7±1.5, F=12.981, P=0.000) and postoperative pain score of 1 hour (group Q: 2.0±0.9, group D: 1.8±0.8, group F: 4.3±0.9, F=42.362, P=0.000) in the group Q and group D were significantly lower than in group F. The body movements in group Q and group D were significantly less than in group F (3 cases, 3 cases, 9 cases, χ2=6.400, P=0.041 ). Intraoperative respiratory depression in group Q and group D were lower than group F (3 cases, 2 cases, 9 cases, χ2=8.012, P=0.018). Conclusions: Oxycodone hydrochloride can be used safely and effectively for radiofrequency ablation. It has favorable hemodynamic stability, lower incidence of respiratory depression, and advantage in terms of postoperative pain.

Impact of abuse-deterrent OxyContin on prescription opioid utilization.

PURPOSE: We quantified the degree to which the August 2010 reformulation of abuse-deterrent OxyContin affected its use, as well as the use of alternative extended-release and immediate-release opioids. METHODS: We used the IMS Health National Prescription Audit, a nationally representative source of prescription activity in the USA, to conduct a segmented time-series analysis of the use of OxyContin and other prescription opioids. Our primary time period of interest was 12 months prior to and following August 2010. We performed model checks and sensitivity analyses, such as adjusting for marketing and promotion, using alternative lag periods, and adding extra observation points. RESULTS: OxyContin sales were similar before and after the August 2010 reformulation, with approximately 550 000 monthly prescriptions. After adjusting for declines in the generic extended-release oxycodone market, the formulation change was associated with a reduction of approximately 18 000 OxyContin prescription sales per month (p = 0.02). This decline corresponded to a change in the annual growth rate of OxyContin use, from 4.9% prior to the reformulation to -23.8% during the year after the reformulation. There were no statistically significant changes associated with the sales of alternative extended-release (p = 0.42) or immediate-release (p = 0.70) opioids. Multiple sensitivity analyses supported these findings and their substantive interpretation. CONCLUSIONS: The market debut of abuse-deterrent OxyContin was associated with declines in its use after accounting for the simultaneous contraction of the generic extended-release oxycodone market. Further scrutiny into the effect of abuse-deterrent formulations on medication use and health outcomes is vital given their popularity in opioid drug development.

Effects of patient medication requests on physician prescribing behavior: results of a factorial experiment.

BACKGROUND: Because of internet searches, advice from friends, and pharmaceutical advertising, especially direct-to-consumer advertising, patients are increasingly activated to request medications during a physician encounter. OBJECTIVES: To estimate the effect of patient requests for medications on physician-prescribing behavior, unconfounded by patient, physician, and practice-setting factors. RESEARCH DESIGN: Two experiments were conducted among 192 primary care physicians, each using different video-based scenarios: an undiagnosed "patient" with symptoms strongly suggesting sciatica, and a "patient" with already diagnosed chronic knee osteoarthritis. Half of patients with sciatica symptoms requested oxycodone, whereas the other half requested something to help with pain. Similarly, half of knee osteoarthritis patients specifically requested celebrex and half requested something to help with pain. SUBJECTS: To increase generalizability and ensure sufficient numbers were available, we recruited 192 primary care physicians from 6 US states. MEASURES: The primary outcome was whether physicians would accede to a patient's request for a medication. Alternative pain medications prescribed were secondary outcomes. RESULTS: 19.8% of sciatica patients requesting oxycodone would receive a prescription for oxycodone, compared with 1% of those making no specific request (P = 0.001). Fifty-three percent of knee osteoarthritis patients requesting celebrex would receive it, compared with 24% of patients making no request (P = 0.001). Patients requesting oxycodone were more likely to receive a strong narcotic (P = 0.001) and less likely to receive a weak narcotic (P = 0.01). Patients requesting celebrex were much less likely to receive a nonselective nonsteroidal anti-inflammatory drugs (P = 0.008). No patient attributes, physician, or organizational factors influenced a physician's willingness to accede to a patient's medication request. CONCLUSIONS: In both scenarios, activated patient requests for a medication substantially affected physician-prescribing decisions, despite the drawbacks of the requested medications.

Candidate metrics for evaluating the impact of prescriber education on the safe use of extended-release/long-acting (ER/LA) opioid analgesics.

OBJECTIVE: The objective of this study was to develop metrics to assess opioid prescribing behavior as part of the evaluation of the Extended-Release/Long-Acting (ER/LA) Opioid Analgesic Risk Evaluation and Mitigation Strategies (REMS). DESIGN: Candidate metrics were selected using published guidelines, examined using sensitivity analyses, and applied to cross-sectional rolling cohorts of Medicare patients prescribed with extended-release oxycodone (ERO) between July 2, 2006 and July 1, 2011. Potential metrics included prescribing opioid-tolerant-only ER/LA opioid analgesics to non-opioid-tolerant patients, prescribing early fills to patients, and ordering drug screens. RESULTS: Proposed definitions for opioid tolerance were seven continuous days of opioid usage of at least 30 mg oxycodone equivalents, within the 7 days (primary) or 30 days (secondary) prior to first opioid-tolerant-only ERO prescription. Forty-four percent of opioid-tolerant-only ERO episodes met the primary opioid tolerance definition; 56% met the secondary definition. Fills were deemed "early" if a prescription was filled before 70% (primary) or 50% (secondary) of the prior prescription's days' supply was to be consumed. Five percent (primary) and 2% (secondary) of episodes had more than or equal to two early fills during treatment. At least one drug screen was billed in 14% of episodes. Stratified analyses indicated that older patients were less likely to be opioid tolerant at the time of the first opioid-tolerant-only ERO prescription. CONCLUSIONS: Investigators propose three metrics to monitor changes in prescribing behaviors for opioid analgesics that might be used to evaluate the ER/LA Opioid Analgesics REMS. Low frequencies of patients, particularly those >85 years, were likely to be opioid tolerant prior to receiving prescriptions for opioid-tolerant-only ERO.

Patient preference with respect to QoL and reduction in opioid-induced constipation (OIC) after treatment with prolonged-release (PR) oxycodone/naloxone compared with previous analgesic therapy [PREFER study].

OBJECTIVE: The aim of this study was to assess patient preference in terms of quality of life (QoL), analgesia and bowel function for patients with moderate to severe chronic non-malignant pain, when treated with oxycodone PR/naloxone PR compared with the previous WHO-step I and/or WHO-step II analgesic treatment . STUDY DESIGN: This was a 3-week open-label phase 3b study conducted in Belgium and the Netherlands, after 3 weeks patients could enter an extension phase. Patient preference with respect to QoL for oxycodone PR/naloxone PR treatment compared with previous WHO-step I and/or WHO-step II analgesics was assessed. A patient was considered a responder with respect to QoL if this assessment was 'better' or 'much better' compared with previous WHO-step I or II analgesics at any time point. RESULTS: Response rate with respect to QoL was 59.2% (95% CI: 51.7-66.8%) for the Full Analysis (FA)-population, for the Per Protocol-population response rate was 71.7% (95% CI: 63.1-80.3%). Explorative analysis showed that response rate with respect to QoL was highest in constipated patients pretreated with WHO-step II analgesics (73.8%). Mean ± SD pain score in the FA-population at start was 74.7 ± 16.6 decreasing to 53.9 ± 24.3 after a median (range) treatment period of 173.5 (31-771) days. For constipated subjects the significant reduction in constipation [improvement of the Bowel Function Index (BFI)], was -24.8 points (95% CI: -17.1 to -32.5). BFI for non-constipated subjects remained well below 28.8. Adverse events with oxycodone PR/naloxone PR treatment were well-known opioid-related adverse events. CONCLUSION: This study shows that the studied patients previously treated with WHO-step I and/or WHO-step II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to QoL. Moreover, the study shows that treatment with oxycodone PR/naloxone PR significantly reduces OIC in constipated patients and that non-constipated patients do not develop OIC during treatment with oxycodone PR/naloxone PR.