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.

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.

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.

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.

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.

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.

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.

The impact of pain on quality of life and the unmet needs of pain management: results from pain sufferers and physicians participating in an Internet survey.

Pain is one of the most common medical complaints, but despite its prevalence, many individuals still suffer with unrelieved or undertreated pain. This marketing research survey was designed to determine the physical, psychological, and economic impact pain has on the lives of individuals suffering with pain and to identify the unmet needs of patients who have taken opioid medications to treat their pain. In addition, the survey sought to address the challenges physicians face when treating patients with pain. Pain sufferers were recruited through e-mail invitation to an Internet survey; 173,854 invitations were sent out, 22,018 people responded (12.7%), and 606 met the criteria for inclusion in the survey as pain sufferers. Of these, 359 people had moderate to moderately severe chronic pain and 247 people had moderate to moderately severe acute pain. Additionally, physicians currently treating pain were recruited through e-mail and postal mail invitations and 492 met eligibility criteria: 241 specialists (orthopedic or general surgeons, pain specialists or anesthesiologists), 125 primary care, and 126 emergency medicine physicians. Results of this survey supported what many physicians observe in their practice and hear from their patients, that pain has a negative impact on daily activities in the majority of pain sufferers. Many chronic pain sufferers reported that pain had deleterious effects on their mental health, employment status, sleep, and personal relationships. The impact of pain on patient quality of life and the unmet needs in pain management were recognized by the majority of physicians surveyed, with inadequate pain control, end-of-dose pain, and side effects associated with increased dosing reported as negative factors influencing their choice of pain medication. In conclusion, effective communication between physicians and patients is encouraged to not only improve overall pain management but also to establish shared treatment goals with functional outcomes.

Rheumatic diseases in the elderly: dealing with rheumatic pain in extended care facilities.

Pain in elderly patients is often underreported, underdiagnosed, and undertreated. Increased understanding of the experience of pain in older persons, strategies for assessment, and appropriate use of pharmacologic and nonpharmacologic approaches is necessary to improve management of pain in this population. This article discusses how issues related to pain in the elderly should be approached, how elderly people perceive pain, how pain in the elderly is assessed, and the various pharmacologic and nonpharmacologic approaches for relieving pain. Finally, the article discusses how pain care for the elderly might be improved.

Cannabinoids:their role in pain and palliation.

Controversy is associated with the issue of cannabis and cannabinoids in clinical care in the United States. Recent research has demonstrated the underlying mechanisms of cannabinoid analgesia via endocannabinoids, an endogenous system of retrograde neuromodulatory messengers that work in tandem with endogenous opioids. Additional receptor and non-receptor mechanisms of cannabinoid drugs have pertinent activity, including anti-carcinogenesis and neuroprotection, that may be of key importance in aging and terminal patient populations. The results of clinical trials with synthetic and plant-based cannabinoids suggest that the role of formulation and delivery system is critical in optimizing the risk-benefit profile of cannabinoid products. Synergy between opioids and cannabinoids may produce opioid-sparing effects, as well as extend the duration of analgesia and reduce opioid tolerance and dependence. This article reviews the mechanism of action of cannabinoids, examines marketed agents and those in clinical trials, and addresses their role in treatment of chronic pain, cancer, neurodegenerative diseases, and HIV/ AIDS. The ability of cannabinoid medicines to treat pain, associated sleep disorders, appetite loss, muscle spasm and a wide variety of other symptoms suggests that such agents may in the future play an important role in palliative care.

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.

Diabetic peripheral neuropathic pain: case studies.

Three case reports in this article illustrate the diagnostic methods used and the treatment course encountered for many patients with diabetic peripheral neuropathic pain (DPNP). Each case addresses an aspect of DPNP: pain that appears to be refractory to initial therapy, DPNP occurring with other medical conditions, and nondiabetlc neuropathy occurring in patients with diabetes mellitus. Together, these cases bring clarity to the confusing clinical experience for patients who have decreased sensation in combination with burning pain, and they apply the consensus guidelines for DPNP. Recently approved medications by the Food and Drug Administration for the treatment of DPNP offer hope for many patients whose pain was thought to be refractory to treatment.

Consensus guidelines: treatment planning and options. Diabetic peripheral neuropathic pain.

Despite the number of patients affected by diabetic peripheral neuropathic pain (DPNP), little consensus exists about the pathophysiology, best diagnostic tools, and primary treatment choices. Theories about the causes of DPNP are inextricably linked with the causes of diabetic neuropathles, yet most patients with such neuropathies do not experience pain. The factors that differentiate patients with pain from those without remain unknown and are the subject of much research. When choosing treatment for patients with DPNP, physicians are confronted with a myriad of choices, none of which has been shown to be effective for all patients. This article reviews the evidence for these treatments and attempts to guide physicians in choosing those treatments based on evidence from well-designed clinical trials to support their use. Two agents, duloxetine and pregabalin, are formally approved by the Food and Drug Administration for the treatment of DPNP. In addition, several other agents, including the tricyclic class of antidepressants, have been effective in clinical trials. Ultimately, treatment choice must also Include consideration of adverse effects, individual patient factors such as comorbidities, and often cost.

Consequences of neuropathic pain: quality-of-life issues and associated costs.

Pain is the primary reason for patients seeking healthcare, and it has been estimated to result in more than dollar 100 billion per year in direct medical costs. Neuropathic pain (NP) alone has been associated with an approximately 3-fold increase in use of healthcare resources. The indirect costs associated with chronic pain result from increased absenteeism and decreased productivity at work, and they also have been estimated to total dollar 100 billion each year in the United States. NP contributes substantially to these costs. Results from one study indicated that employment was affected in 43% of patients with NP. Quality of life is also significantly reduced in such patients. Patients with chronic pain also have difficulty in initiating and maintaining sleep, and sleep deprivation has the potential to exacerbate pain. Sleep deprivation is also associated with both anxiety and depression, and both of these conditions can exacerbate sleep disturbances. Effective management of the patient with chronic pain, including NP, requires assessment and, if necessary, treatment of all comorbidities associated with this condition.

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.

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.

Rheumatic diseases in the elderly: dealing with rheumatic pain in extended care facilities.

Rheumatic diseases representing over 100 conditions are common in elderly people, are increasing in frequency, and are undertreated. Extended care facilities have special needs and restrictions, making pain management more complicated. Understanding how to assess pain in a population at risk for poor pain control is vital. Treatment individualized to the patient's special circumstances where optimal care rarely means cure or complete relief of symptoms leads to improved function and quality of life.

A systems approach to identifying inappropriate use of controlled substances: the need for balance.

BACKGROUND: The diversion, abuse, and inappropriate use of controlled substances remain of concern among health care practitioners, insurers, and policy makers in the United States. The principle of "balance" represents a need to establish a system of control to prevent abuse, trafficking, and diversion of controlled substances, while ensuring their medical availability for legitimate patients. ADMINISTRATIVE DATABASES TO STUDY OUTCOMES AND QUALITY OF CARE: Some models employ pattern recognition within administrative health databases, for example, to examine outcomes and quality of medical care and monitor fraudulent behaviors and inappropriate medical care. Patients' use of resources or variations in practitioners' practice patterns can be examined. A SYSTEMS APPROACH TO ADDRESS INAPPROPRIATE USE OF CONTROLLED SUBSTANCES: A systems approach would require collaboration with medical and pharmacy directors, systems analysts, coding experts, legal experts, and clinicians to develop the claims-based model. Once a patient and/or practitioner with possible diversion or abuse are identified, a second step is required to distinguish inappropriate and appropriate behaviors and medical care. CONCLUSION: Programs to detect misuse of controlled substances must be validated through clinical research, and a consensus should be reached as to what constitutes a breach of accepted medical practice.

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.