Use Of Opioid Analgesics Research Articles

The Modified WHO Analgesic Ladder: Is It Appropriate for Chronic Non-Cancer Pain?

IntroductionFrom 1986, the World Health Organization (WHO) analgesic ladder has been used as the simple and valuable pain-relieving guidance in the pharmaceutical pain management, however, with the development of medical history, notions about pain physiology and pain management have already updated. Is the analgesic ladder still appropriate for chronic non-cancer pain (CNCP) patients? This study aims to analyse the current usage of the analgesic ladder in patients with CNCP by evaluating previously published pertinent studies.MethodsLiterature published in English from January 1980 to April 2019 and cited on PubMed database was included. Analysis on the analgesic ladder, current status of CNCP management, and a new revised ladder model were developed based on relevant literature.ResultsThe WHO analgesic ladder for cancer pain is not appropriate for current CNCP management. It is revised into a four-step ladder: the integrative therapies being adopted at each step for reducing or even stopping the use of opioid analgesics; interventional therapies being considered as step 3 before upgrading to strong opioids if non-opioids and weak opioids failed in CNCP management.DiscussionA simple and valuable guideline in past years, the WHO analgesic ladder is inappropriate for the current use of CNCP control. A revised four-step analgesic ladder aligned with integrative medicine principles and minimally invasive interventions is recommended for control of CNCP.

A systematic review of the evidence for the efficacy of opioids for chronic non-cancer pain in community-dwelling older adults

the ageing global population and concomitant increase in the use of opioid analgesia have highlighted the need to evaluate the effectiveness of opioids for chronic pain in older people. a systematic review of the evidence for the efficacy of opioids for chronic non-cancer pain in community-dwelling people aged 65years or more was conducted using PRISMA guidelines. The databases MEDLINE, EMBASE, Pubmed and PsychINFO were searched. The quality of studies was assessed. Secondary aims were to assess correlates of opioid use and the decision-making processes of prescribers. seven studies were identified of low to high quality. The majority of older people experienced ongoing pain despite continuing opioid therapy. There were mixed results regarding benefits of opioids in terms of activities of daily living and social engagement. In nursing home residents, opioid use at baseline was associated with severe pain, severe impairment in activities of daily living and a diagnosis of depression. Fear of causing harm to older people was common amongst opioid prescribers, limiting prescription. Facilitators of opioid prescription included educational interventions and access to an evidence base for opioid use. there is limited evidence supporting the use of long-term opioid use in older people for chronic non-cancer pain and a lack of trials in this age group. Age-specific guidelines are required addressing initial assessment, indications, monitoring and de-prescribing.

Surgeon-Administered Nerve Block During Rotator Cuff Repair Can Promote Recovery with Little or No Post-operative Opioid Use

BackgroundThe use of opioid analgesia is common in both the acute and extended post-operative periods after rotator cuff repair. The current opioid crisis has prompted surgeons to seek alternatives that minimize or even eliminate the need for oral opioids after surgery.Questions/PurposesWe sought to investigate the effects on post-operative opioid use of a surgeon-administered block of the suprascapular and axillary nerves in arthroscopic rotator cuff repair (ARCR), in particular to quantify outpatient opioid consumption and duration.MethodsIn this prospective observational study, all patients undergoing primary ARCR performed under general anesthesia by a single surgeon were studied over a 15-month period. Of 91 ARCRs performed, 87 patients were enrolled and followed prospectively. At the conclusion of the procedure, the surgeon performed “local–regional” nerve blockade with injections to the sensory branches of the suprascapular nerve and the axillary nerve, as well as local infiltration about the shoulder. Use of medications in the post-anesthesia care unit was left up to the anesthesiologist. Patients were prescribed oral opioids (hydrocodone/acetaminophen 5/325 mg) for analgesia after discharge. The quantity and duration of opioid use and pain scores were recorded for 4 months. Statistical analysis was performed to evaluate factors that could account for greater opioid use.ResultsTotal opioid consumption ranged from 0 to 30 opioid tablets (average, 4.2 tablets) over the 4-month period. Post-operatively, 91% of patients took between ten or fewer tablets, and 39% took no opioids. The average duration of opioid use was 2.4 days. No patients were taking opioids at the 4- to 6-week or 4-month follow-up visits, none required refills, and none received prescriptions from outside prescribers. No statistically significant differences were seen in opioids taken or duration of use in regard to tear size, sex, body mass index, surgery location, or procedure time. There was a significant inverse correlation between opioid use and age. In addition, the cost of the surgeon-performed procedure was substantially lower than that associated with pre-operative nerve blockade performed by an anesthesiologist. All patients were satisfied with the post-operative pain management protocol. Average reported post-operative pain scores were low and decreased at each visit.ConclusionWith this local–regional nerve-blocking protocol, opioid use after ARCR was unexpectedly low, and a large proportion of patients recovered without any post-surgical opioids. The correlation seen between opioid use and age may not be clinically significant, given the low use of post-operative opioids overall. These results may be useful in guiding post-operative opioid prescribing after ARCR, as well as in lowering costs associated with ARCR.

Local anaesthesia for haemorrhoidal rubber band ligation reduces immediate post-operative recovery time and use of opioid analgesia.

Haemorrhoidal rubber band ligation (RBL) is a well-established, safe and cost-effective treatment for bleeding haemorrhoids. It is generally well tolerated; however, some patients may require narcotic analgesia or even admission to hospital for pain management. This comparative cohort study reports on the difference in peri-procedural analgesia administration and post-operative recovery time between patients who received local anaesthetic (LA) infiltration in addition to RBL, compared with patients treated only with RBL. Consecutive patients with haemorrhoids treated over a 3-month period with LA infiltration in addition to RBL were compared to a consecutive control group who received RBL alone in the preceding 3 months. Clinical data were collected prospectively for LA group and retrospectively for the control group. Data collected included analgesia administered during the procedure and in recovery, as well as the mean time to discharge. A total of 32 patients treated with LA infiltration following RBL for haemorrhoids were compared with 22 patients who were treated with RBL alone. There was a reduction in the administration of intra-procedural parecoxib in the LA group (P < 0.001). Following the procedure, there was a reduction in the administration of both oral and intravenous opioid analgesia (P = 0.009) and reduced mean time to discharge in the LA group (P < 0.001). Infiltration of LA proximal to the band following RBL for haemorrhoids reduced the administration of analgesia both during the procedure and in recovery, as well as mean time to discharge following the procedure.

The Prescription Opioids and Depression Pathways Cohort Study.

BackgroundResults from studies using medical record data indicate chronic (>90 days) opioid analgesic use (OAU) is associated with new depressive episodes (NDE), worsening depression and risk for depression recurrence. This body of evidence is based on retrospective cohort studies and medical record data. Limitations of existing research are overcome in a new prospective cohort study of the opioid-depression relationship.MethodsProspective cohort of 1500 adult patients recruited from two health care systems. Eligible subjects started a new period of OAU and have 30 to 90 days of OAU at baseline. Diagnostic assessments for psychiatric disorders, structured measures of pain, pain functioning, opioid use, social support, sleep and impulsivity will be obtained at baseline, 6-month and 12-month follow-up. Baseline participants will be invited to 12 monthly brief assessments of pain-related functioning, depression symptoms and opioid use.InnovationRobust control for confounding by indication and detailed phenotyping of depression and opioid use disorder.Anticipated resultsChronic OAU will be associated with new onset of a depression phenotype characterized by anhedonia and somatic symptoms. This relationship will be partly, but not completely explained by impaired functioning and low social support.ConclusionsAlthough the annual number of opioid prescriptions in the United States has decreased, over 190 million patients have OAU each year. If chronic OAU leads to a clinically meaningful affective disorder, independent of pain, then we need to consider depression an important adverse effect of chronic OAU and adjust care for chronic pain accordingly.

A model for an institutional response to the opioid crisis.

The use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. Physicians, policymakers, and researchers are focused on finding ways to decrease opioid use and overdose. This crisis calls for a coordinated response that includes the entire healthcare sector. In this work, the authors lay out a blueprint for such a response at the level of the academic medical center. The proposed model is a comprehensive opioid overdose prevention, response, and education program to evaluate, monitor, and address prescription opioid-related adverse events and addiction among all patients within a healthcare system. The approach includes three inter-related elements: (1) creation of an organizational structure that is subdivided into subcommittees to facilitate cross-functional collaboration and implementation. These subcommittees will focus on Research and Design, Implementation, Advisory, and Compliance with the recommendation. (2) Development of an effective communication plan throughout the institution to enable the organization to function seamlessly and efficiently as a single unit, (3) development of a data tracking and reporting system that intended to have a 360° view of all aspects of opioid prescription and downstream patient outcomes. The most effective response system will require an organizational structure that facilitates the ad hoc constitution of cross-functional teams with members drawn from all levels of the organizational hierarchy (executive leadership to frontline staff). Such a structure provides the teams with immediate solutions as developed by the frontline staff and authority to remove institutional barriers that may delay or limit the successful implementation. The model described was developed in our institution by a cross-functional team that included members from the Johns Hopkins School of Medicine and Johns Hopkins University Carey Business School, Department of Operations Management. The multidisciplinary nature of collaboration allowed us to develop a model for an immediate institution-wide response to the opioid crisis, and one that other healthcare organizations could adopt with local modification as a template for execution. The model also meant to serve as a template for an institutional rapid-response that can be seamlessly implemented during any future drug-related crisis or epidemic.

Low Dose Ketamine Used for Acute Pain Management in the Emergency Department

The use of opioid analgesics has created an opioid addiction epidemic in the United States and around the world. One of the main responsibilities of the emergency department is to address acute pain. In this paper we examine the use of low dose ketamine as a safe substitute for opioid analgesics. Types of pain are identified using prior established taxonomy, followed by discussing types of management and treatments. The opioid epidemic and its societal implications are considered. We also examine the side effects of ketamine and the use of ketamine as an adjunct to analgesics used for pain control. Recommendations and considerations for the use of ketamine are suggested, and a low dose ketamine administration sample hospital policy is reviewed.

Incentive spirometry to prevent pulmonary complications after chest trauma: a retrospective observational study.

Pulmonary complications (PCs) are a major cause of poor prognosis in chest trauma. Evidence on the effectiveness of incentive spirometry (IS) in trauma is scarce. This study investigated the effectiveness of IS in preventing PCs in patients with chest trauma with rib fractures. This retrospective observational study analyzed the data obtained from the electronic medical records of patients with chest trauma with rib fractures admitted between 2011 and 2019. We included patients 18years of age or older with risk of worsening respiratory failure. Early IS was the primary exposure and PCs (pulmonary infection or respiratory failure requiring escalating oxygen therapy) were the primary outcomes. Secondary outcomes were length of hospital stay, duration of oxygenation therapy, and adverse events of IS. Logistic regression analysis with a propensity score was used. We extracted 514 patients from the electronic medical records; 299 patients were included. The early IS group had a higher proportion of hypoxemia at admission, opioid analgesia use, invasive positive pressure ventilation, and respiratory physiotherapy. The severity of trauma was higher in the early IS group. There was no significant difference in the occurrence of the PCs between groups (adjusted odds ratio 0.71; 95% confidence interval, 0.24-2.16). No statistical differences were seen in the secondary outcomes. For patients with chest trauma with rib fractures at risk of worsening respiratory failure, IS early after injury did not reduce the rate of PCs. No adverse event of IS was observed and IS was shown to be safe.

Opioid prescribing practices in a pediatric burn tertiary care facility: Is it time to change?

Opioids are the mainstay therapy in burned adults. Little data in the pediatric burn population exists that elucidates opioid prescribing practices. The primary purpose of this report is to quantify opioid and non-opioid analgesic use in pediatric burn patients admitted to a tertiary referral burn center. A retrospective audit of hospital charts and discharge records for patients <18 years old from March 2016 to March 2017 was performed. Opioid amounts were converted to either oral morphine miligram equivalents (MME) or oral MME per day and subsequently adjusted for age in kilograms (kg). Of the 226 patients, 223 (98.7%) were administered an opioid during admission. The median total opioid amount administered during admission was 0.4 (IQR: 0.3–0.6) mg oral MME per kilogram per day. Anecdotally, doses above 1 mg/kg/day are considered high risk for opioid tolerance. The median total opioid amount prescribed upon discharge was high at 3.9 (IQR: 2.3, 5.6) mg of oral MME per kilogram. Hydrocodone (96.0%) was the most common opioid administered, followed by morphine (88.1%). The most commonly prescribed discharge opioid was hydrocodone (95.4%). Non-opoioid analgesia during admission was used in 112 patients (49.6%). This study provides novel insight into the opioid practices at a tertiary burn center for pediatric patients, with our analysis showcasing high usage of opioids during admission and discharge for burn analgesia. It emphasizes the need to expand beyond opioids for burn analgesia and the importance of promoting non-opioid, multimodal analgesia in the pediatric burn population.

Opioid-related deaths in Europe: Strategies for a comprehensive approach to address a major public health concern

Use of illicit opioids and misuse of prescription opioids are the main causes of drug-related deaths across the world, and the continuing rise in opioid-related mortality, especially affecting North America, Australia and Europe, is a public health challenge. Strategies that may help to decrease the high levels of opioid-related mortality and morbidity and improve care across Europe include risk assessment and interventions to improve the use of opioid analgesics, e.g. prescription drug-monitoring programmes, education on pain management to reduce opioid prescribing, and the implementation of evidence-based primary prevention programmes to reduce the demand for opioids. For patients who develop opioid use disorder (a chronic and relapsing problematic use of opioids that causes clinical impairment or distress), treatment combining opiate receptor full or partial agonist medications for opioid-use disorder (MOUD) with psychosocial interventions is essential.However, in Europe a substantial proportion of the 1.3 million high-risk opioid users (defined as injecting drug use or regular use of opioids, mainly heroin) remain outside of dedicated treatment programmes. More widespread and easier access to MOUD could reduce mortality levels; via approaches such as primary care-led treatment models, and efforts to improve patient retention and adherence to treatment programmes. Other harm-reduction strategies, such as the use of MOUD at optimal doses, the provision of take-home naloxone, the introduction of supervised drug-consumption facilities, and patient education to reduce the risk of overdose may also be beneficial.

Collaborating With a Spinal Interventionalist in the Management of Low Back Pain

Low back pain is the primary cause of adult disability worldwide and if poorly managed can precipitate the unnecessary use of opioids, diminish physical functioning, and lead to comorbid conditions interfering with patient quality of life. Providers who collaborate with a spinal interventionalist can effectively manage acute and chronic low back pain, improve physical functioning, and reduce the use of opioid analgesics. The implementation of specific spinal interventions, adjuvant analgesics, and collaboration with a multidisciplinary team can promote health and wellness for 1 of the most prevalent and debilitating global health conditions.

The Trends in Opioid Use in Castile and Leon, Spain: A Population-Based Registry Analysis of Dispensations in 2015 to 2018.

Opioids are driving-impairing medicines (DIM). To assess the evolution and trends of opioid analgesics use between 2015 and 2018 in Castile and Leon (Spain), a population-based registry study was conceived. The length of opioid use and its concomitant use with other DIMs were studied. Analyses were done considering age and gender distributions. Adjusted consumption for licensed drivers is also presented. Of the 5 million dispensations recorded between 2015 and 2018, opioid analgesics were dispensed to 11.44% of the general population and 8.72% of vehicle drivers. Increases among daily users (2.6 times higher) and chronic users (1.5% higher) were noted, supporting the overall increase in opioid use (1.5%). The use of multiple drugs including other DIMs was a common finding (mean ± SD, 2.54 ± 0.01). Acute use (5.26%) and chronic use (3.20%) were also frequent. Formulations combining opioid analgesics with nonopioid analgesics were preferred. The use of opioids increased in Spain between 2015 and 2018. Concomitant use with other DIMS especially affects women and the elderly. Frequent use of opioid analgesics with other DIMs is a serious problem for drivers and increases the risk of accidents. Promoting safe driving should be a main objective of health authorities, to be achieved by developing and implementing educational activities for healthcare professionals and patients.

Maternal prescribed opioid analgesic use during pregnancy and associations with adverse birth outcomes: A population-based study.

Published research on prescribed opioid analgesic (POA) use during pregnancy and birth outcomes is limited in scope and has not adequately adjusted for potential confounding factors. To help address these gaps, we estimated associations between maternal POAs during pregnancy and two adverse birth outcomes using a large population-based dataset, multiple definitions of POA exposure, and several methods to evaluate the influence of both measured and unmeasured confounding factors. We obtained data by linking information from several Swedish registers and conducted a retrospective cohort study on a population-based sample of 620,458 Swedish births occurring between 2007 and 2013 (48.6% female; 44.4% firstborn). We evaluated associations between prenatal POA exposure and risk for preterm birth (PTB; <37 gestational weeks) and small for gestational age (SGA; birth weight 2 standard deviations below the expected weight for gestational age or lower). We evaluated the influence of confounding by adjusting for a wide range of measured covariates while comparing exposed and unexposed infants. Additionally, we adjusted for unmeasured confounding factors by using several advanced epidemiological designs. Infants exposed to POAs anytime during pregnancy were at increased risk for PTB compared with unexposed infants (6.4% exposed versus 4.4% unexposed; adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.31-1.45, p < 0.001). This association was attenuated when we compared POA-exposed infants with acetaminophen-exposed infants (OR = 1.18, 95% CI 1.07-1.30, p < 0.001), infants born to women who used POAs before pregnancy only (OR = 1.05, 95% CI 0.96-1.14, p = 0.27), and unexposed siblings (OR = 0.99, 95% CI 0.85-1.14, p = 0.92). We also evaluated associations with short-term versus persistent POA use during pregnancy and observed a similar pattern of results, although the magnitudes of associations with persistent exposure were larger than associations with any use or short-term use. Although short-term use was not associated with SGA (adjusted ORsingle-trimester = 0.95, 95% CI 0.87-1.04, p = 0.29), persistent use was associated with increased risk for SGA (adjusted ORmultiple-trimester = 1.40, 95% CI 1.17-1.67, p < 0.001) compared with unexposed infants. The association with persistent exposure was attenuated when we used alternative comparison groups (e.g., sibling comparison OR = 1.22, 95% CI 0.60-2.48, p = 0.58). Of note, our study had limitations, including potential bias from exposure misclassification, an inability to adjust for all sources of confounding, and uncertainty regarding generalizability to countries outside of Sweden. Our results suggested that observed associations between POA use during pregnancy and risk of PTB and SGA were largely due to unmeasured confounding factors, although we could not rule out small independent associations, particularly for persistent POA use during pregnancy.

Association between postoperative complications and lingering post-surgical pain: an observational cohort study

BackgroundPost-surgical pain that lingers beyond the initial few-week period of tissue healing is a major predictor of pain chronification, which leads to substantial disability and new persistent opioid analgesic use. We investigated whether postoperative medical complications increase the risk of lingering post-surgical pain. MethodsThe study population consisted of patients undergoing diverse elective surgical procedures in an academic referral centre in the USA, between September 2013 and May 2017. Multivariable logistic regression, adjusting for confounding variables and patient-specific risk factors, was used to test for an independent association between any major postoperative complication and functionally limiting lingering pain 1–3 months after surgery, as obtained from patient self-reports. ResultsThe cohort included 11 986 adult surgical patients; 10 562 with complete data. At least one complication (cardiovascular, respiratory, renal/gastrointestinal, wound, thrombotic, or neural) was reported by 13.3% (95% confidence interval: 12.7–14.0) of patients, and 19.7% (19.0–20.5%) reported functionally limiting lingering post-surgical pain. After adjusting for known risk factors, the patients were twice as likely (odds ratio: 2.04; 1.78–2.35) to report lingering post-surgical pain if they also self-reported a postoperative complication. Experiencing a complication was also independently predictive of lingering post-surgical pain (odds ratio: 1.95; 1.26–3.04) when complication data were extracted from the National Surgical Quality Improvement Program registry, instead of being obtained from patient self-report. ConclusionsMedical complications were associated with a two-fold increase in functionally limiting pain 1–3 months after surgery. Understanding the mechanisms that link complications to pathological persistence of pain could help develop future approaches to prevent persistent post-surgical pain.

Opioid Analgesics Do Not Improve Abdominal Pain or Quality of Life in Crohn's Disease.

Abdominal pain and opioid analgesic use are common in Crohn's disease (CD). We sought to identify factors associated with abdominal pain in CD and evaluate the impact of opioid analgesics on pain and quality-of-life scores in this setting. We performed a longitudinal cohort study using a prospective, consented IBD natural history registry from a single academic center between 2009 and 2013. Consecutive CD patients were followed for at least 1year after an index visit. Data were abstracted regarding pain experience (from validated surveys), inflammatory activity (using endoscopic/histologic findings), laboratory studies, coexistent psychiatric disorders, medical therapy, opioid analgesic, and tobacco use. Of 542 CD patients (56.6% women), 232 (42.8%) described abdominal pain. Individuals with pain were more likely to undergo surgery and were more frequently prescribed analgesics and/or antidepressants/anxiolytics. Elevated ESR (OR 1.79; 95%CI 1.11-2.87), coexistent anxiety/depression (OR 1.87; 95%CI 1.13-3.09), smoking (OR 2.08; 95%CI 1.27-3.40), and opioid use (OR 2.46; 95%CI 1.33-4.57) were independently associated with abdominal pain. Eighty patients (14.8%) were prescribed opioids, while 31 began taking them at or after the index visit. Patients started on opioids demonstrated no improvement in abdominal pain or quality-of-life scores on follow-up compared to patients not taking opioids. Abdominal pain is common in CD and is associated with significant opioid analgesic utilization and increased incidence of anxiety/depression, smoking, and elevated inflammatory markers. Importantly, opioid use in CD was not associated with improvement in pain or quality-of-life scores. These findings reinforce the limitations of currently available analgesics in IBD and support exploration of alternative therapies.

A study of the use of post-operative opioid analgesics following rhinology surgery in 35 patients

Opioid analgesics are often prescribed following rhinology surgery. This study aimed to evaluate whether the quantity of opioid analgesics prescribed is justified. Patients were asked about their pain management post-operatively. Parameters recorded included: current pain (using a 10-point Likert scale); type of operation; the opioid analgesics prescribed; and the quantity of opioid tablets taken and other methods of pain relief used. Thirty-five patients were successfully contacted. The median pain score at one week post-operation was 1 (interquartile range, 0-3). Of these 35 patients, 16 were prescribed opioids, whilst 19 were not. Patients prescribed opioids took a median of 8 tablets (interquartile range, 0.8-10.5) out of the 28 tablets prescribed. The study shows that the quantity of post-operative opioid analgesics prescribed does not compare with the amount consumed by patients to relieve pain, resulting in a surplus of opioid medication which has the potential to be abused.

Real-World Efficacy of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria in South Korea: Paradox of Eculizumab

Purpose Eculizumab is reported to be highly effective in managing patients with paroxysmal nocturnal hemoglobinuria (PNH). However, eculizumab therapy is associated with high cost and thus is inaccessible to all patients with PNH. Additionally, there are some restrictions in the coverage of PNH therapy from the health insurance, which varies depending on each country. In South Korea, majority of the cost involved in eculizumab therapy is supported by the National Health Insurance Service (NHIS) with very limited indication. The patients with PNH must satisfy all of the following criteria to be eligible for financial support from NIHS: (1) PNH granulocyte count ≥ 10%; (2) lactate dehydrogenase ≥ 1.5 times the upper limit of normal; (3) at least 4 units of red blood cells must have be transfused in the past 12 months (transfusion-dependent anemia (TDA)); and (4) exhibit at least more than one of the PNH-related complications (except TDA), which include thrombosis, renal insufficiency, pulmonary insufficiency, or recurrent smooth muscle spasm. These criteria are the narrowest indication for eculizumab therapy compared with those used by other countries. Hence, we performed a nation-wide study including all the patients with PNH in South Korea using the NHIS database to investigate the real-world efficacy of eculizumab. Methods The National Health Insurance Database of the NHIS in South Korea was used to collect the data of patients diagnosed with PNH between January 1, 2002 and December 31, 2016. Propensity score (PS) method was used to evaluate the real-world effects of eculizumab on patient survival. For PS method, the patients with PNH were divided into the following two groups: (1) patients treated with eculizumab; and (2) patients not treated with eculizumab. Additionally, the patients used for the analysis were limited to those who are surviving from the time of introduction of eculizumab in South Korea (October 1, 2012). In total, 11 variables were selected for PS matching according to the indications for using eculizumab in South Korea: age, sex, TDA, venous thrombosis, arterial thrombosis, AA, MDS, acute renal failure (ARF), chronic renal failure (CRF), prescription of opioid analgesic drug (≥ 2 times), and pulmonary hypertension. The patients diagnosed with acute leukemia were excluded. The time point of the matching was designated as the date on which the eculizumab was first administered. All survival or complication analyses were performed using the Cox proportional hazard regression model. The duration of PNH was used as the explanatory variable to estimate the proper treatment effect. Results Eculizumab-treated patients exhibited significantly higher survival rate than the eculizumab-untreated patients (4-year survival after propensity score matching, 98.31% vs. 79.67%, p = 0.0489). The mean RBC transfusion units per 12 months after eculizumab therapy was significantly lower than that before eculizumab therapy (5.75 units vs. 12.28 units, p &lt; 0.0001). The median time for the first transfusion in the eculizumab-treated group was significantly longer than that in the eculizumab-untreated group (p = 0.0078). The 4-year transfusion-independence rate for the eculizumab-treated group was significantly higher than that for the eculizumab-untreated group (20.81%; 95% CI, 10.71-33.20%, vs. 10.24%; 95% CI, 4.17-19.50%). There was no significant difference in the incidence of new documented complications related to PNH between the two groups. These complications include venous thrombosis (p = 0.886), arterial thrombosis (p = 0.112), acute renal failure (p = 0.745), chronic renal failure (p = 0.827), use of opioid analgesics (p = 0.142), and pulmonary hypertension (p = 0.396). Conclusions Eculizumab therapy for high-risk PNH patients may effectively improve the survival rate and reduce the transfusion requirement. Paradoxically, the eculizumab-treated patients with severe PNH exhibit higher survival rate than the eculizumab-untreated patients with less severe PNH. Disclosures No relevant conflicts of interest to declare.

Opioid Analgesics Are Associated with Albuminuria in Adult Patients with Sickle Cell Anemia

Introduction: Sickle cell disease (SCD) is characterized by hemolytic anemia and vaso-occlusive episodes associated with multi-organ dysfunction. Chronic kidney disease is a common complication and associated with increased mortality. Opioid analgesics are used in SCD patients for pain relief, often starting at a young age and continuing through adulthood. In SCD mouse models, chronic opioid exposure worsens nephropathy leading to increased glomerular mesangial volume and fractional kidney mass as well as albuminuria. We evaluated the association of opioid analgesic use and albuminuria in adult patients with sickle cell disease. Methods: We conducted a cross-sectional study of patients with sickle cell anemia (HbSS and HbSβ0thalassemia) recruited into a prospective natural history cohort at two adult Sickle Cell Centers. Patients were enrolled during routine clinic visits and in a non-crisis, "steady state". We excluded patients with bone marrow or kidney transplant, diabetic nephropathy, hepatitis B or C, HIV, lupus or other glomerular diseases and those on dialysis. We collected data on treatment including use of hydroxyurea and ACE-inhibitors or angiotensin receptor blockers (ACE-I/ARB). Opioid exposure was determined from state narcotic databases for each patient during the year preceding enrollment. Clinical laboratory tests, including spot urine albumin-creatinine ratio (UACR), were acquired at the baseline visit. Patients were considered to have albuminuria if UACR was ≥30mg/g creatinine. Total opioid use, converted to morphine-equivalent units, was quantified in the preceding 1 month, 6 months, and 12 months. Morphine exposure in each time interval was categorized into three groups for analysis: no morphine exposure, exposure ≤50thpercentile, and exposure &gt;50thpercentile. We used multivariable logistic regression models to assess the relationship between opioid use categories and presence of albuminuria adjusting for the following covariates: age, sex, hydroxyurea use, ACE-I/ARB use, total bilirubin, direct bilirubin, hemoglobin, white blood cell (WBC) count, systolic and diastolic blood pressure, hemoglobin F%, estimated glomerular filtration rate (eGFR) and site of enrollment. Results: Seventy-eight patients with sickle cell anemia who had complete data for the variables of interest and outcome were included. Mean age was 33.1 years (SD 11.5) and 45 (57.7 %) were female. When comparing patients by albuminuria status (Table), patients with albuminuria were older (36.1 v 30.8 years) and less likely to be female (45.5 % v 66.7 %). Patients with albuminuria had both higher systolic and diastolic blood pressures. Hydroxyurea use was similar between both groups, but albuminuria patients were more likely to receive ACE-I/ARB therapy. Patients with albuminuria were more likely to have lower hemoglobin, higher total bilirubin, alkaline phosphatase and absolute reticulocyte count. Patients with albuminuria also had lower eGFR and greater opioid exposure over each of the three time intervals evaluated. Opioid use in the preceding 1 month was not associated with albuminuria in the adjusted model (p=0.6). Opioid use in the preceding 6 months was associated with albuminuria (p=0.02), patients with opioid exposure &gt;50thpercentile (&gt;5500 mg of morphine equivalent) having a 39.1 (95% CI: 2.1, 719.8; p=0.01) higher odds of developing albuminuria compared to those without opioid exposure. Patients with less than the 50thpercentile also trended towards a higher odds of albuminuria (OR 6.3, 95% CI: 0.7, 58.1; p=0.1), but did not reach statistical significance. As estimates for odds of albuminuria were similar for patients with &gt; 50thpercentile and ≤50thpercentile of opioid exposure over twelve months of exposure, we collapsed the categories into "no opioid exposure" vs. "any opioid exposure." Patients with any amount of opioid use over the preceding 12 months had a higher odds of albuminuria (OR 11.0, 95% CI 1.2, 104.4; p=0.04). Conclusion: While limited in sample size, our data demonstrate that higher opioid exposure over the preceding 6 months and any opioid exposure in the preceding year were independently associated with albuminuria in patients with sickle cell anemia. These findings suggest that opioid exposure may be associated with kidney disease in patients with SCD. This association warrants additional study given the common use of these agents in SCD. Disclosures Derebail: Retrophin: Consultancy; RTI: Honoraria; Novartis: Consultancy. Ataga:Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Modus Therapeutics: Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer

Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 μg (n = 56), 100 μg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.

80. Opioid Analgesics Are Associated with Increased Clostridioides difficile Infection Risk in a National Cohort of Veterans

Background Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea. Several drugs are known to increase CDI risk, although the association between opioids and CDI risk has not been clearly established. Opioid analgesics have gastrointestinal antimotility and immunomodulatory effects, which may predispose patients to infection. The purpose of this study was to determine the association between opioid use and CDI risk.MethodsThis was a retrospective case–control study that utilized inpatient and outpatient data from the national United States Veterans Health Administration (VHA). CDI patients included those age 18 to 89 years with an ICD-9-CM code for CDI (008.45), a positive stool test, and active CDI therapy between October 1, 2002 and September 30, 2014. A control cohort of VHA patients was created by randomly sampling patients without a CDI ICD-9-CM code during the study period and matched to CDI patients by visit setting and fiscal year. Opioid use was defined as at least one prescription for morphine, hydromorphone, hydrocodone, and/or codeine in the 90 days prior to study inclusion. The χ 2 test was used to compare the proportion of patients who received an opioid in the CDI and control groups. Opioid risk factors for CDI were analyzed using a multivariable logistic regression model that included 33 covariates.ResultsA total of 85,451 patients were included in this study (26,149 CDI patients and 59,302 controls). Overall, 50.1% and 30.1% of patients were prescribed an opioid in the CDI and cohort group, respectively. Overall, opioids were associated with significantly increased CDI risk (OR 1.92, 95% CI 1.86–2.00) and was even greater for >1 opioid (OR 2.40; 95% CI 2.25–2.55). Opioids with the strongest association with CDI risk include morphine (OR 2.04, 95% CI 1.95–2.13), followed by hydromorphone (OR 1.74, 95% CI 1.63–1.87), codeine (OR 1.56, 95% CI 1.44–1.70), and hydrocodone (OR 1.14; 95% CI 1.09–1.19).ConclusionIn a national cohort of veterans, patients with recent opioid analgesic use had an increased risk of developing CDI compared with a control group. Opioid analgesics with greater immunomodulatory and constipating effects were associated with increased risk compared with other opioids.Disclosures All Authors: No reported Disclosures.