The use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19.

Early in the COVID-19 pandemic, anecdotal reports emerged suggesting non-steroidal anti-inflammatory drugs (NSAIDs) may increase susceptibility to infection and adversely impact clinical outcomes. This narrative literature review (March 2020-July 2021) attempted to clarify the relationship between NSAID use and COVID-19 outcomes related to disease susceptibility or severity. Twenty-four relevant publications (covering 25 studies) reporting original research data were identified; all were observational cohort studies, and eight were described as retrospective. Overall, these studies are consistent in showing that NSAIDs neither increase the likelihood of SARS-CoV-2 infection nor worsen outcomes in patients with COVID-19. This is reflected in current recommendations from major public health authorities across the world, which support NSAID use for analgesic or antipyretic treatment during COVID-19. Thus, there is no basis on which to restrict or prohibit use of these drugs by consumers or patients to manage their health conditions and symptoms during the pandemic.

Rational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain: Consensus Recommendations.

Objective: To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. Methods: An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Results: Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from validated risk assessment tools, and previous UDM. Urine drug monitoring is suggested to be performed at baseline for most patients prescribed opioids for chronic pain and at least annually for those at low risk, two or more times per year for those at moderate risk, and three or more times per year for those at high risk. Additional UDM should be performed as needed on the basis of clinical judgment. Conclusions: Although evidence on the efficacy of UDM in preventing opioid use disorder, overdose, and diversion is limited, UDM is recommended by the panel as part of ongoing comprehensive risk monitoring in patients prescribed opioids for chronic pain.

Dose-response of pregabalin for diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.

OBJECTIVES: The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. METHODS: Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. RESULTS: In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. CONCLUSION: The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.

Variations in the management of fibromyalgia by physician specialty: rheumatology versus primary care.

PURPOSE: To evaluate the effect of physician specialty regarding diagnosis and treatment of fibromyalgia (FM) and assess the clinical status of patients initiating new treatment for FM using data from Real-World Examination of Fibromyalgia: Longitudinal Evaluation of Costs and Treatments. PATIENTS AND METHODS: Outpatients from 58 sites in the United States were enrolled. Data were collected via in-office surveys and telephone interviews. Pairwise comparisons by specialty were made using chi-square, Fisher's exact tests, and Student's t-tests. RESULTS: Physician specialist cohorts included rheumatologists (n=54), primary care physicians (n=25), and a heterogeneous group of physicians practicing pain or physical medicine, psychiatry, neurology, obstetrics and gynecology, osteopathy, or an unspecified specialty (n=12). The rheumatologists expressed higher confidence diagnosing FM (4.5 on a five-point scale) than primary care physicians (4.1) (P=0.037). All cohorts strongly agreed that recognizing FM is their responsibility. They agreed that psychological aspects of FM are important, but disagreed that symptoms are psychosomatic. All physician cohorts agreed with a multidisciplinary approach including nonpharmacological and pharmacological treatments, although physicians were more confident prescribing medications than alternative therapies. Most patients reported moderate to severe pain, multiple comorbidities, and treatment with several medications and nonpharmacologic therapies. CONCLUSION: Physician practice characteristics, physician attitudes, and FM patient profiles were broadly similar across specialties. The small but significant differences reported by physicians and patients across physician cohorts suggest that despite published guidelines, treatment of FM still contains important variance across specialties.

An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: alternative modes of administration to facilitate pain management in patients with dysphagia.

BACKGROUND: Patients with chronic pain may experience difficulty swallowing, in part due to worsening disease, comorbid conditions, iatrogenic etiology, or age. Patients or caregivers may manipulate extended-release (ER) opioid formulations to facilitate oral dosing due to a lack of therapeutic options that allow for sprinkle or enteral feeding tube administration. If crushed or broken, current oral ER opioids can be associated with adverse sequelae, including risk of potentially fatal overdose. OBJECTIVE: To review the safety, in vitro dissolution data, and in vivo pharmacokinetic data that support alternative modes of administration of oxycodone DETERx (Xtampza ER) via sprinkling onto soft foods for oral ingestion or via enteral feeding tubes. METHODS: A review of oxycodone DETERx data from in vitro and in vivo studies was conducted to demonstrate support for alternative routes and modes of administration. RESULTS: There was no difference in the dissolution profile when administered with various soft foods or when mixed with various liquid vehicles and administered via nasogastric (NG) or gastrostomy (G) tubes, based on in vitro studies. When sprinkled onto applesauce and administered orally, the microspheres were bioequivalent to the intact oxycodone capsules. When crushed or chewed, the formulation maintained its pharmacokinetic profile; no bolus dose of opioid was released. The sprinkle-dose study was limited by the single-dose study design, as well as the small sample size. CONCLUSIONS: Oxycodone DETERx is the first ER oxycodone formulation that can be administered either intact, sprinkled onto soft foods, or via NG/G tubes, thereby providing options for treating pain in patients who have difficulty swallowing.

The complexity model: a novel approach to improve chronic pain care.

OBJECTIVE: More than 25% of the US population experiences chronic pain; yet few physicians specialize in the field of pain medicine. This article will review a theoretical model of care that stratifies treatment and patients by level and type of complexity and promotes communication between specialist and primary care providers. DISCUSSION: The undertreatment of pain was recently brought to national attention to encourage both clinicians and patients to advocate for improved pain care. The specialty of pain medicine and models of care, challenges of managing pain in a primary care setting, and the reliance on an opioid-focused approach are reviewed. An evolved model of pain care based on the complexity of pain and emphasizing a dynamic collaboration between the primary care provider and the pain specialist is discussed. CONCLUSIONS: From the perspective of the busy clinician, the treatment of chronic pain can be overwhelming. The scarcity of trained pain practitioners and the burgeoning number of patients with chronic pain necessitate a new approach that values the complex nature of chronic pain and offers a practical blueprint to meet these challenges.

Evolving therapeutic strategies to improve nonsteroidal anti-inflammatory drug safety.

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess potent anti-inflammatory and analgesic properties through inhibition of cyclooxygenase enzymes (COX-1 and COX-2), which are responsible for synthesis of proinflammatory mediators. NSAIDs are frequently used for treatment of acute and chronic pain conditions. However, their use is associated with serious dose-dependent gastrointestinal (GI), cardiovascular, renal, and hepatic adverse effects, which pose a serious clinical concern for both patients and physicians. During the past 2 decades, approaches to improving the tolerability of NSAIDs were mainly directed toward discovery of COX-2 selective NSAIDs (coxibs), which were expected to minimize the risk of GI injury. Unfortunately, the results from multiple clinical studies have shown that treatment with coxibs may increase the risk for cardiovascular complications. This review summarizes current strategies used to reduce the toxicity of NSAIDs and outlines novel therapeutic approaches still in preclinical development. To minimize the risk of GI ulcerations and bleeding, combination therapies with gastroprotective agents are currently recommended. The new therapeutic agents anticipated to have similar effects include nitric oxide- and hydrogen sulfide-releasing NSAIDs. Novel manufacturing technologies enhance dissolution and absorption of NSAID products, allowing for their administration at low doses, which could lead to improved drug tolerability without diminishing the analgesic and anti-inflammatory efficacy of NSAIDs. This principle is in line with the current recommendation by the US Food and Drug Administration that NSAIDs should be used at the lowest effective dosage. Finally, NSAID formulations targeted directly to the site of inflammation are expected to reduce systemic drug exposure and thus decrease the risk of systemic adverse effects.

Clinicians' perspective on the use of immunoassay versus definitive laboratory quantitation methodologies for medication monitoring.

Treating chronic pain is complicated. Primary care doctors and others are called on to treat the vast majority of patients with pain, to do so in brief visits and to do it safely. This is a tall order, but it is possible to do it well when the proper tools are employed to aid the clinician in diagnosing and monitoring the patient. Among these tools, the one that has been most useful is urine drug testing. Prescribers can perform presumptive screens with the immunoassay method in my office, but this method has limitations in accuracy and specificity and sensitivity. When medically necessary, it makes sense to seek definitive testing from the laboratory to confirm results of immunoassay tests with chromatographic testing and/or when there is the possibility of a false negative in the office. These "false negatives" are extremely common, with patients using nonprescribed opioids and illicit medications often go undetected if one were to stop at the office-based result. These patients are in danger of addiction and overdose, and this added information is crucial in efforts to treat pain and avoid these complications.

NSAIDs in the older patient: balancing benefits and harms.

OBJECTIVE: The older person is more likely to have pain since degenerative diseases and the effects of cancer are more common after 65 years of age. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used due to perceived safety, relatively low cost and over-the-counter availability. This brief review describes the necessity for, but risks of, NSAIDs in the older patient. DESIGN: A literature search was undertaken using PubMed and search terms including pain, aging, treatment, nonsteroidal anti-inflammatory drugs, arthritis, older patient, and guidelines. CONCLUSIONS: Pain complaints are common in the older population. Low back pain and osteoarthritis affects over two thirds of this group. Patients and clinicians are increasingly wary about treatment since no medication appears to be safe. Older patients opting for no treatment may have worsening function including decreased sleep, mobility, socialization, and increased depression. Ninety percent of all prescription NSAIDs are taken by patients over 65. Guidelines for safe use are available but frequently not followed by the practitioner including the FDA recommended "lowest dose possible for your treatment … for the shortest time needed." NSAIDs can be an effective treatment option for many older persons but caution should be exercised in this often fragile population.

Integrating health information technology and electronic health records into the management of fibromyalgia.

Fibromyalgia (FM) is a widespread chronic pain condition that represents a significant economic burden for patients and health care systems. Effective treatment of FM requires a multidisciplinary management strategy that incorporates pharmacologic and nonpharmacologic therapy. Steps such as reducing the time to diagnosis and improving treatment decisions can result in significant cost savings and improved patient outcomes. An FM management framework, based on patient education and goal setting, has emphasized the need for ongoing care of patients with FM. In this article, we discuss how this framework could be further improved through the use of health information technology, including electronic health records. Health information technology/electronic health records can be incorporated at every stage of patient care, from initial presentation to diagnosis, through to making treatment decisions and maintaining ongoing patient management. This can lead to a number of potential benefits for patients with FM (by improving their level of care), primary care providers (by creating greater efficiencies), and the health care system (by reducing costs). Ultimately, the treatment and care of patients with FM need be no more burdensome to primary care providers than any other chronic illness. Through the greater efficiencies and optimized treatment approaches facilitated by health information technology/electronic health records, it should be possible to drive best-practice care for patients with FM and improve patient outcomes.

Physician management of moderate-to-severe acute pain: results from the Physicians Partnering Against Pain (P³) study.

OBJECTIVE: To evaluate differences among physician specialties in the management of acute pain including prescribing practices and management of opioid-related side effects. DESIGN AND PARTICIPANTS: The Physicians Partnering Against Pain (P³) survey was a nationwide study of US physicians and their patients with severe to moderate acute pain (<3 months). MAIN MEASURES: Physicians were surveyed about volume of patients with moderate-to-severe acute pain in their practice, frequency of prescribing opioid analgesics, percentage of these patients returning for a follow-up visit after treatment, reasons patients discontinue treatment, frequency of recommending or prescribing treatment for opioid-related gastrointestinal (GI) side effects, and frequency of patients taking opioid analgesics that take additional treatments to manage GI side effects. RESULTS: The 5,982 participating physicians represented primary care physicians (PCPs; 52 percent), pain specialists (25 percent), and other specialists (23 percent). PCPs and other specialists were less likely than pain specialists to prescribe opioid analgesics to patients (25.8 percent, 29.5 percent, and 44.8 percent, respectively). The vast majority of pain specialists (78 percent) also indicated that more than three quarters of their patients returned for a follow-up visit compared with only 40 percent of PCPs and 65 percent of other specialists. When ranking the reasons why they think patients discontinue opioid analgesics, pain specialists ranked unacceptable side effects higher than PCPs and other specialists. PCPs and pain specialists were more likely than other specialists to recommend or prescribe treatments to manage opioid-related side effects, such as nausea, vomiting, and constipation (38.3 percent, 38.5 percent, and 23.1 percent, respectively). CONCLUSION: The P(3) Study confirms the challenge of pain management while balancing tolerability of opioid treatments from the physician perspective.

Comprehensive chronic pain management: improving physical and psychological function (CME multimedia activity).

As shown in this CME online activity (www.cmeaccess.com/AJM/ChronicPain02), chronic, non-cancer pain can arise from a variety of etiologies and can be broadly classified based on its underlying mechanism as nociceptive, inflammatory, neuropathic, or central, with some patients having pain arising from a combination of mechanisms. Chronic pain assessment and treatment involves evaluating not only its biological aspects, but also psychological and sociocultural factors. Beyond neural mechanisms, a patient's perception of chronic pain can be influenced by comorbid mood disorders, such as depression and anxiety; cognitive and affective traits, such as catastrophizing and fear-avoidance; environmental stressors, family relationships, social support, and cultural beliefs. Based on this biopsychosocial model, a multidisciplinary approach to management incorporates pharmacotherapy (opioid, nonopioid, and centrally-acting analgesics, and pain adjuvant medications) with nonpharmacologic physical rehabilitation and psychological and behavioral therapies to address the multifactorial causes of chronic pain, which in turn leads to improvement of physical and psychological function.

Managing chronic pain with nonopioid analgesics: a multidisciplinary consult.

As detailed in this online CME activity (www.cmeaccess.com/AJM/ChronicPain04), determining pain mechanism is an important aspect guiding treatment selection for chronic musculoskeletal pain states. Although broad classifications provide a framework, any combination of mechanisms may be present in a chronic pain patient, and there is growing evidence that pain states generally considered nociceptive may also involve elements of augmented central nervous system pain processing. Nonopioid analgesics, including serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and alpha-2-delta ligand anticonvulsants, are the treatments of choice for fibromyalgia and other central neuropathic pain states. Additionally, studies have now shown that certain SNRIs can be effective in treating "classic" nociceptive pain states, such as osteoarthritis, and also are effective for low back pain. In addition to considering biological mechanisms, chronic pain management also involves recognizing and evaluating the contribution of psychological and sociocultural factors that can influence pain chronicity and patient prognosis. A multimodal/multidisciplinary approach incorporating pharmacologic and nonpharmacologic therapy into a program that includes more than 1 discipline is important to improve outcomes in patients with chronic pain.

A randomized, 14-day, double-blind study evaluating conversion from hydrocodone/acetaminophen (Vicodin) to buprenorphine transdermal system 10 µg/h or 20 µg/h in patients with osteoarthritis pain.

OBJECTIVE: The objective of this study was to evaluate continued pain control and tolerability of converting patients from Vicodin (hydrocodone/acetaminophen; HCD/APAP) to the buprenorphine transdermal system (BTDS). METHODS: Adult patients with pain from osteoarthritis receiving a stable dosage of HCD/APAP (i.e., 15 - 30 mg hydrocodone/day) were switched to an equivalent or near-equivalent dosage of open-label Vicodin for 7 days. Patients maintaining acceptable analgesia were stratified based on their Vicodin dosage and randomized to receive either titratable BTDS 10 µg/h or fixed-dose BTDS 20 µg/h. The primary efficacy variable was completion of the 14-day double-blind phase. Tolerability was assessed. RESULTS: A total of 84.3% of patients met the primary end point, completion of the 14-day double-blind phase (167/198 patients, 95% CI 79.3 - 89.4). Adverse events were consistent with those associated with the use of opioid analgesics and transdermal patches. CONCLUSION: There was a similar analgesic and tolerability profile when patients treated with Vicodin for osteoarthritis pain were switched to 7-day BTDS treatment.

Clinical overview of fibromyalgia.

Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide, more frequently in women than in men. In addition to chronic widespread pain, patients with FM usually experience other characteristic symptoms, including fatigue, disturbed sleep, stiffness, reduced functioning, dyscognition, and depressed mood. Many patients also have comorbid conditions such as depression, irritable bowel syndrome, temporomandibular disorder, or migraine. Although the etiology of FM remains unclear, evidence suggests that biologic, genetic, and environmental factors are involved. The variability of symptoms and the frequency of comorbidities among patients with FM make this a difficult disorder to diagnose. Diagnosis may be further complicated by the stigmatization of this disorder among treatment providers, the health insurance industry, and the general population. Treating chronic pain disorders such as FM can be time consuming and costly, and other issues such as polypharmacy, treatment adherence, and access to treatment often need to be addressed. The aim of this article is to provide physicians with a general overview of FM, including a brief review of the pathophysiology that explains the biologic and genetic bases of this disorder. Also included is a synopsis of new diagnostic criteria and other useful diagnostic tools and a discussion of various treatment challenges and strategies.

Diagnosis and treatment of low-back pain because of paraspinous muscle spasm: a physician roundtable.

BACKGROUND: Despite the availability of evidence-based guidelines to diagnose and treat acute low-back pain, practical application is nonuniform and physician uncertainty regarding best practices is widespread. OBJECTIVE: The objective of this study was to further optimal treatment choices for screening, diagnosing, and treating acute low-back pain caused by paraspinous muscle spasm. METHODS: Four experts in pain medicine (three family physicians and one physiatrist) participated in a roundtable conference call on October 18, 2010, to examine current common practices and guidelines for diagnosing and treating acute low-back pain and to offer commentary and examples from their clinical experience. RESULTS: Participants discussed the preferred choices and timing of diagnostic and imaging tests, nonpharmacologic therapies, nonopioid and opioid medication use, biopsychosocial evaluation, complementary therapies, and other issues related to treatment of acute low-back pain. Principal clinical recommendations to emerge included thorough physical exam and medical history, early patient mobilization, conservative use of imaging tests, early administration of muscle relaxants combined with nonsteroidal anti-inflammatory medications to reduce pain and spasm, and a strong emphasis on patient education and physician-patient communication. CONCLUSIONS: Early, active management of acute low-back symptoms during the initial onset may lead to better patient outcomes, reducing related pain and disability and, possibly, preventing progression to chronicity.

A critical assessment of opioid treatment adherence using urine drug testing in chronic pain management.

OBJECTIVE: To determine the current status of performing urine drug tests (UDTs) for monitoring chronic pain therapy, with an emphasis on their use in opioid treatment and the need for improved physician education about UDTs. RESULTS: Although opioids are commonly used in the treatment of chronic pain, their use is associated with an increased risk for drug abuse, addiction, diversion, and overdose in chronic pain patients. Thus, adherence with opioid therapy is central to optimal chronic pain management. Patient observation (ie, early refills, pill counts, etc.) is the least effective method of assessing opioid medication adherence. Urine drug tests, such as point-of-care (POC) tests and laboratory urine tests (LUTs) employing gas chromatography/mass spectrometry or liquid chromatography mass spectrometry and liquid chromatography tandem mass spectrometry, have recently been used. Point-of-care immunoassays are commonly used to assess treatment adherence, especially in primary care. However, POC tests are less specific and less sensitive than LUTs and are more likely to give false-negative or false-positive results, increasing the risk of excluding a patient from therapy due to an erroneous diagnosis. In contrast, LUTs provide quantitative measurement of a wider range of medications and their metabolites, and represent a more precise tool for monitoring drug adherence. They are, however, more difficult to interpret and more expensive. Physicians are generally unaware of the relative merits of POC tests and LUTs, their implementation, and interpretation of adherence data. CONCLUSION: Despite the acknowledged utility of UDTs, there is a critical need for physician education on the use of different UDTs for adherence monitoring because early detection of opioid nonadherence is key to optimal chronic pain management.

Chronic pain: reducing costs through early implementation of adherence testing and recognition of opioid misuse.

OBJECTIVE: To review the literature on costs associated with chronic pain therapy and to identify key contributing factors. Also, to assess the potential cost-saving benefits of monitoring pain treatment adherence using urine drug tests (UDTs), emphasizing their use in opioid therapy. RESULTS: Reduced productivity, compensation costs, and treatment of comorbid conditions related to chronic pain contribute to the substantial financial burden of chronic pain management in the United States. The growing use of opioids for chronic pain increases the risk for drug nonadherence and associated drug abuse, potential addiction, and aberrant drug-related behaviors (ADRBs). Treatment of drug abuse increases health care costs; opioid abusers are 25 times more likely to require hospitalization than nonopioid abusers. Early detection of patient nonadherence using UDTs could significantly reduce costs of chronic pain therapy by allowing the physician to identify and treat patients' ADRBs related to controlled substances and drug addiction and abuse problems. Adherence in chronic pain may be determined by point-of-care (POC) tests, and more sensitive laboratory urine tests employing gas chromatography/mass spectrometry with high-performance liquid chromatography tests (LUTs). Cost-benefit studies suggest that the cost of LUTs to optimize adherence may reduce costs associated with nonadherence, such as inpatient clinical care and patient self-release. Current estimates indicate that appropriate use of LUTs could produce decreases up to 14.8-fold in the cost of chronic pain therapy. CONCLUSIONS: The cost benefits of UDTs can only be fully realized if physicians know how to define and detect various types of drug abuse, addiction, and diversion. Physicians should be educated on the proper implementation of POC tests and LUTs, and interpretation of adherence data. Early monitoring of drug adherence using POC tests and follow-up LUTs may provide substantial cost savings associated with health care issues incurred in nonadherent chronic pain patients, especially those taking opioid therapy.

Analgesic treatment for moderate-to-severe acute pain in the United States: patients' perspectives in the Physicians Partnering Against Pain (P3) survey.

OBJECTIVES: To evaluate patients' perceptions of the adequacy of analgesia for moderate-to-severe acute pain and the influence of opioid-related side effects in outpatient pain management. SETTING: The Physicians Partnering Against Pain (P3) survey of analgesic treatment for moderate-to-severe acute pain in the United States. PATIENTS: Adults with moderate-to-severe acute pain at their first analgesic followup visit. MAIN OUTCOME MEASURES: Analgesic level was determined from the World Health Organization'spain ladder (0 = none; 1 = nonopioid; 2 = weak opioid; 3 = strong opioid). Pain intensity was derived from numeric rating scale (NRS) scores (0 = none [NRS = 0]; 1 = mild [NRS = 1-3]; 2 = moderate [NRS = 4-7]; 3 = severe [NRS = 8-10). Pain management index scores were calculated as the analgesic level minus the pain intensity. Opioid recipients responded to questions on the P3 survey regarding side effects and their management. RESULTS: Of the 50,869 patients with complete data for analysis, 22,267 (44 percent) had received potentially inadequate analgesia, including 43, 46, and 52 percent of patients aged < 65, 65-74, and > or = 75 years, respectively. Of the 39,6 75 patients treated with an opioid, 10,925 (28 percent) experienced at least one gastrointestinal side effect (nausea, vomiting or constipation). Many of these patients stopped taking the medication (13 percent) or reduced their dose (16 percent) to manage gastrointestinal side effects. CONCLUSIONS: In the P3 study, one of the largest outpatient surveys conducted in pain management, moderate-to-severe acute pain continued to be widely undertreated in outpatient settings in the United States, particularly among older patients. Opioids with improved tolerability profiles might help to alleviate this undertreatment of moderate-to-severe acute pain.