Stefan P. Kruszewski

Ambulatory diagnosis and treatment of nonmalignant pain in the United States, 2000-2010.

Background:Escalating rates of prescription opioid use and abuse have occurred in the context of efforts to improve the treatment of nonmalignant pain. Objective:The aim of the study was to characterize the diagnosis and management of nonmalignant pain in ambulatory, office-based settings in the United States between 2000 and 2010. Design, Setting, and Participants:Serial cross-sectional and multivariate regression analyses of the National Ambulatory Medical Care Survey (NAMCS), a nationally representative audit of office-based physician visits, were conducted. Measures:(1) Annual visit volume among adults with primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3) receipt of prescription opioid or nonopioid pharmacologic therapy in visits for new musculoskeletal pain. Results:Primary symptoms or diagnoses of pain consistently represented one-fifth of visits, varying little from 2000 to 2010. Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%, whereas nonopioid analgesic prescribing remained unchanged (26%–29% of visits). One-half of new musculoskeletal pain visits resulted in pharmacologic treatment, although the prescribing of nonopioid pharmacotherapies decreased from 38% of visits (2000) to 29% of visits (2010). After adjusting for potentially confounding covariates, few patient, physician, or practice characteristics were associated with a prescription opioid rather than a nonopioid analgesic for new musculoskeletal pain, and increases in opioid prescribing generally occurred nonselectively over time. Conclusions:Increased opioid prescribing has not been accompanied by similar increases in nonopioid analgesics or the proportion of ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives to prescription opioids may be underutilized as a means of treating ambulatory nonmalignant pain.

Rethinking Opioid Prescribing to Protect Patient Safety and Public Health

PRESCRIPTION DRUGS, INCLUDING AMPHETAMINES, OPIoids, and benzodiazepines, provide therapeutic value to millions of Americans. At the same time, there are increasing concerns about the skyrocketing rates of prescription abuse and overdose deaths. The annual number of fatal drug overdoses in the United States now surpasses the annual number of motor vehicle deaths, and overdose deaths attributable to prescription opioids—nearly 15 000 in 2008—exceed those attributable to cocaine and heroin combined. These trends have co-occurred while clinicians and policy makers have attempted to improve the undertreatment of chronic pain through efforts such as the “Pain as the 5th Vital Sign” campaign and the promulgation of quality measures by professional organizations. Many of these initiatives do not specifically advocate greater opioid use. However, the initiatives have coexisted with, and in some cases been supported by, a pharmaceutical industry in which increasing sales of opioids have grossed billions of dollars. A recent senatorial inquiry hints at the opaque flow of funding from industry to consumer and advocacy organizations that promote increased use of pain medication. To address the increasing epidemic of opioid abuse, a variety of strategies have been implemented, including limits on the number of opioid prescriptions covered by insurers, requirements that these drugs be supplied through a single physician or pharmacy, and state prescription drug monitoring programs. Despite these efforts, reduction of opioid abuse may not succeed until there is a broader clinical shift from such widespread use of these medicines. There are clear correlations between national trends for prescription opioid sales, admissions for substance abuse treatment, and deaths. Between 1999 and 2010, each of these has steadily and inexorably increased in parallel with the others. This suggests that substantial increases in the nonmedical use of opioids is a predictable adverse effect of substantial increases in the extent of prescriptive use. Under current regulatory and market conditions, it is likely that a significant and increasing amount of opioids produced to meet clinical demand will be misused or diverted from the legal to illegal markets, leading to more addiction and death. This has important implications for policy makers, because it highlights the difficulty of selectively decreasing abuse and diversion while keeping the overall supply of opioids for legitimate use constant or increasing. To curtail the current epidemic of opioid abuse, overdoses, and related deaths, regulatory and enforcement measures to prevent nonmedical use and diversion should be complemented by changes to clinical guidelines to treat chronic pain that are less reliant on opioids. A public health approach to the treatment of pain in the context of an epidemic of abuse would place greater weight on considering the harmful effects, or what economists consider to be negative externalities, that clinicians’ treatment decisions have on other individuals beyond the individual patient being treated. There are sources of diversion of opioids at every step in the supply chain, and some observers have argued that because the majority of opioid addicts report that their access to the drugs is through friends or family rather than physicians, the misuse of these therapies may not be considered a “clinical problem.” Publicity regarding robberies of warehouses storing opioid medications serves to reinforce the perception that physician practices, aside from “pill mills,” are not of concern. Such reasoning fails to consider that increased access of opioids through friends and family is due, in part, to the increasing prescribing of medications commonly diverted for illicit use. Greater clinical judiciousness is especially warranted given the limited evidence to support many clinical applications in which opioids are used. For example, although opioids may be efficacious for acute lower back pain, the safety, efficacy, and abuse data are limited for chronic back pain. There are serious gaps in the knowledge base regarding opioid use for other chronic nonmalignant pain as well, including a lack of randomized trials that have active treatment groups or that examine major harms and benefits of

Prevalence and treatment of pain in EDs in the United States, 2000 to 2010

OBJECTIVESnTo describe changes in the prevalence and severity of pain and prescribing of non-opioid analgesics in US emergency departments (EDs) from 2000 to 2010.nnnMETHODSnAnalysis of serial cross-sectional data regarding ED visits from the National Hospital Ambulatory Medical Care Survey. Visits were limited to patients ≥18 years old without malignancy. Outcome measures included annual volume of visits among adults with a primary symptom or diagnosis of pain, annual rates of patient-reported pain severity, and predictors of non-opioid receipt for non-malignant pain.nnnRESULTSnRates of pain remained stable, representing approximately 45% of visits from 2000 through 2010. Patients reported pain as their primary symptom twice as often as providers reported a primary pain diagnosis (40% vs 20%). The percentage of patients reporting severe pain increased from 25% (95% confidence intervals [CI] 22%-27%) in 2003 to 40% (CI 37%-42%) in 2008. From 2000 to 2010, the proportion of pain visits treated with pharmacotherapies increased from 56% (CI 53%-58%) to 71% (CI 69%-72%), although visits treated exclusively with non-opioids decreased 21% from 28% (CI 27%-30%) to 22% (CI 20%-23%). The adjusted odds of non-opioid rather than opioid receipt were greater among visits for patients 18 to 24 years old (odds ratio [OR] 1.35, CI 1.24-1.46), receiving fewer medicines (OR 2.91, CI 2.70-3.15) and those with a diagnosis of mental illness (OR 2.24, CI 1.99-2.52).nnnCONCLUSIONSnLarge increases in opioid utilization in EDs have coincided with reductions in the use of non-opioid analgesics and an unchanging prevalence of pain among patients.

Trends in the use of buprenorphine by office-based physicians in the United States, 2003–2013

BACKGROUND AND OBJECTIVESnDespite buprenorphines promise as a novel therapy for opioid dependence, little is known about its clinical adoption. We characterized trends in ambulatory use of buprenorphine in the United States.nnnMETHODSnCross-sectional, descriptive analyses of buprenorphine utilization from 2003 to 2013 using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory care. The primary unit of analysis was an office visit where buprenorphine was used for opioid dependence (treatment visit).nnnRESULTSnBetween 2003 and 2013, there was significant uptake of buprenorphine in ambulatory treatment visits, from 0.16 million [M] (95% confidence interval [CI] 0.10-0.20) visits in 2003 to 2.1M (CI 1.9-2.3M) treatment visits during 2013. Approximately 90% involved the use of brand name combination buprenorphine/naloxone (Suboxone), although this percentage decreased modestly to 80% by the last quarter of 2013. Buprenorphine prescribing increased among all specialties, but the proportion accounted for by primary care physicians increased significantly from 6.0% in 2003 to 63.5% in 2013 and decreased among psychiatrists from 92.2% to 32.8% over the same time period.nnnCONCLUSIONSnThe use of buprenorphine products to treat opioid dependence has increased significantly in the past 10 years and has shifted to greater use by primary care physicians, indicating a rapidly changing face of opioid maintenance therapy in the United States.

Primary care physicians' knowledge and attitudes regarding prescription opioid abuse and diversion

Objectives:Physicians are a key stakeholder in the epidemic of prescription opioid abuse. Therefore, we assessed their knowledge of opioid abuse and diversion, as well as their support for clinical and regulatory interventions to reduce opioid-related morbidity and mortality. Materials and Methods:We conducted a nationally representative postal mail survey of 1000 practicing internists, family physicians, and general practitioners in the United States between February and May 2014. Results:The adjusted response rate was 58%, and all physicians (100%) believed that prescription drug abuse was a problem in their communities. However, only two-thirds (66%) correctly reported that the most common route of abuse was swallowing pills whole, and nearly one-half (46%) erroneously reported that abuse-deterrent formulations were less addictive than their counterparts. In addition, a notable minority of physicians (25%) reported being “not at all” or “only slightly concerned” about the potential for opioid diversion from the licit to the illicit market when this practice is common at all levels of the pharmaceutical supply chain. Most physicians supported clinical and regulatory interventions to reduce prescription opioid abuse, including the use of patient contracts (98%), urine drug testing (90%), requiring prescribers to check a centralized database before prescribing opioids (88%), and instituting greater restrictions on the marketing and promotion of opioids (77% to 82%). Despite this, only one-third of physicians (33%) believed that interventions to reduce prescription opioid abuse had a moderate or large effect on preventing patients’ clinically appropriate access to pain treatment. Discussion:Although physicians are unaware of some facets of prescription opioid-related morbidity, most support a variety of clinical and regulatory interventions to improve the risk-benefit balance of these therapies.

Quality of evidence in drug compendia supporting off-label use of typical and atypical antipsychotic medications

Public and private payers use drug compendia to make coverage determinations, yet the quality of evidence they contain has received little scrutiny. We examined compendia citations regarding antipsychotic drugs, an important drug class given their substantial costs and widespread use. Nearly three-fold as many off-label indications were recommended for atypical as for typical agents, a difference that did not appear to be due to differences in quality of evidence for typical and atypical off-label indications. Given the important role that compendia play in evidence synthesis, coverage decisions, and ultimately, prescription utilization, these data suggest greater efforts are needed to improve the quality of evidence and transparency of evidence evaluations compendia contain.

Serum Biochemical Parameters Following Heroin Withdrawal: An Exploratory Study

BACKGROUNDnLong-term consumption of opioid compounds, even after withdrawal, affects serum biochemical parameters. Investigating these alterations is a new approach in substance abuse studies.nnnMETHODnThis study investigated clinical laboratory results in men who are currently active, recently abstinent and non-heroin users. Participants (Nu2009=u2009240) of this matched cohort study included heroin dependent men referred for abstinence treatment, volunteer men who did not abuse opioids matched for age, sex, body mass index, and educational level (control group). The groups were further sub-divided for analysis into (a) continuous heroin users for more than 2 years (Nu2009=u200970), the dependent group; (b) heroin abusers with 1 month abstinence period (Nu2009=u200970), identified as ex-heroin dependents; and (c) a matched, non-dependent control group (Nu2009=u2009100). All participants were tested for fasting blood sugar (FBS), sodium, potassium, calcium, uric acid (UA), blood urea nitrogen (BUN), creatinine, total cholesterol, triglycerides (TGs), total protein, fibrinogen, and prothrombin.nnnRESULTSnCompared to the control group, ex-heroin dependents showed decreased FBS and significantly higher sodium, creatinine, and cholesterol levels. Compared to the heroin dependent group, the ex-heroin dependents showed significant differences in FBS, sodium, calcium, creatinine, UA, and thrombin time. No significant differences were noted between ex-heroin dependents and controls in potassium, calcium, UA, BUN, TGs, total protein, and thrombin time.nnnCONCLUSIONnThese results demonstrate altered laboratory markers in long-term heroin dependents as well as ex-heroin dependents and suggest the need for further identification, population distribution, and etiological understanding of these biomarkers in individuals who have abused heroin.

Trends in the use of buprenorphine by office-based physicians in the United States, 2003-2013: Buprenorphine Use by Physicians in US, 2003-2013

BACKGROUND AND OBJECTIVESnDespite buprenorphines promise as a novel therapy for opioid dependence, little is known about its clinical adoption. We characterized trends in ambulatory use of buprenorphine in the United States.nnnMETHODSnCross-sectional, descriptive analyses of buprenorphine utilization from 2003 to 2013 using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory care. The primary unit of analysis was an office visit where buprenorphine was used for opioid dependence (treatment visit).nnnRESULTSnBetween 2003 and 2013, there was significant uptake of buprenorphine in ambulatory treatment visits, from 0.16 million [M] (95% confidence interval [CI] 0.10-0.20) visits in 2003 to 2.1M (CI 1.9-2.3M) treatment visits during 2013. Approximately 90% involved the use of brand name combination buprenorphine/naloxone (Suboxone), although this percentage decreased modestly to 80% by the last quarter of 2013. Buprenorphine prescribing increased among all specialties, but the proportion accounted for by primary care physicians increased significantly from 6.0% in 2003 to 63.5% in 2013 and decreased among psychiatrists from 92.2% to 32.8% over the same time period.nnnCONCLUSIONSnThe use of buprenorphine products to treat opioid dependence has increased significantly in the past 10 years and has shifted to greater use by primary care physicians, indicating a rapidly changing face of opioid maintenance therapy in the United States. (Am J Addict 2014;XX:XX-XX).