Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Prescription Opioid Abuse in Chronic Pain: An Updated Review of Opioid Abuse Predictors and Strategies to Curb Opioid Abuse: Part 1.

Chronic pain and prescription opioid abuse are extremely prevalent both in this country and worldwide. Consequences of opioid misuse can be life-threatening with significant morbidity and mortality, exacting a heavy toll on patients, physicians, and society. Individuals with chronic pain and co-occurring substance use disorders and/or mental health disorders, are at a higher risk for misuse of prescribed opioids. Opioid abuse and misuse occurs for a variety of reasons, including self-medication, use for reward, compulsive use because of addiction, and diversion for profit. There is a significant need for treatment approaches that balance treating chronic pain; while minimizing risks for opioid abuse, misuse, and diversion. The use of chronic opioid therapy for chronic non-cancer pain has increased dramatically in the past 2 decades in conjunction with associated increases in the abuse of prescribed opioids and accidental opioid overdoses. Consequently, a validated screening instrument which provides an effective and rational method of selecting patients for opioid therapy, predicting risk, and identifying problems once they arise could be of enormous benefit in clinical practice. Such an instrument could potentially curb the risk of iatrogenic addiction. Although several screening instruments and strategies have been introduced in recent years, there is no single test or instrument which can reliably and accurately predict those patients not suitable for opioid therapy or identify those who need increased vigilance or monitoring during therapy. At present, screening for opioid abuse includes assessment of premorbid and comorbid substance abuse; assessment of aberrant drug-related behaviors; risk factor stratification; and utilization of opioid assessment screening tools. Multiple opioid assessment screening tools and instruments have been developed by various authors. In addition, urine drug testing, monitoring of prescribing practices, prescription monitoring programs, opioid treatment agreements, and utilization of universal precautions are essential. Presently, a combination of strategies is recommended to stratify risk, to identify and understand aberrant drug related behaviors, and to tailor treatments accordingly. This manuscript builds on the 2012 opioid guidelines published in Pain Physician and the 2016 guidelines released by the Centers for Disease Control and Prevention. It reviews the current state of knowledge regarding the growing problem of opioid abuse and misuse; known risk factors; and methods of predicting, assessing, monitoring, and addressing opioid abuse and misuse in patients with chronic non-cancer pain.Key words: Opioids, misuse, abuse, chronic pain, prevalence, risk assessment, risk management, drug monitoring, aberrant drug-related behavior.

Value of Examination Under Fluoroscopy for the Assessment of Sacroiliac Joint Dysfunction.

BACKGROUND: Pain emanating from the sacroiliac (SI) joint can have variable radiation patterns. Single physical examination tests for SI joint pain are inconsistent with multiple tests increasing both sensitivity and specificity. OBJECTIVE: To evaluate the use of fluoroscopy in the diagnosis of SI joint pain. STUDY DESIGN: Prospective double blind comparison study. SETTING: Pain clinic and radiology setting in urban Veterans Administration (VA) in New Orleans, Louisiana. METHODS: Twenty-two adult men, patients at a southeastern United States VA interventional pain clinic, presented with unilateral low back pain of more than 2 months' duration. Patients with previous back surgery were excluded from the study. Each patient was given a Gapping test, Patrick (FABERE) test, and Gaenslen test. A second blinded physician placed each patient prone under fluoroscopic guidance, asking each patient to point to the most painful area. Pain was provoked by applying pressure with the heel of the palm in that area to determine the point of maximum tenderness. The area was marked with a radio-opaque object and was placed on the mark with a fluoroscopic imgage. A site within 1 cm of the SI joint was considered as a positive test. This was followed by a diagnostic injection under fluoroscopy with 1 mL 2% lidocaine. A positive result was considered as more than 2 hours of greater than 75% reduction in pain. Then, in 2-3 days this was followed by a therapeutic injection under fluoroscopy with 1 mL 0.5% bupivacaine and 40 mg methylprednisolone. RESULTS: Each patient was reassessed after 6 weeks. The sensitivity and specificity in addition to the positive and negative predictive values were determined for both the conventional examinations, as well as the examination under fluoroscopy. Finally, a receiver operating characteristic (ROC) curve was constructed to evaluate test performance. The sensitivity and specificity of the fluoroscopic examination were 0.82 and 0.80 respectively; Positive predictive value and negative predictive value were 0.93 and 0.57 respectively. The area under ROC curve was 0.812 which is considered a "good" test; however the area under ROC for the conventional examination were between 0.52-0.58 which is considered "poor to fail". LIMITATIONS: Variation in anatomy of the SI joint, small sample size. CONCLUSIONS: Multiple structures of the SI joint complex can result in clinical symptoms of pain. These include intra-articular structures (degenerative arthritis, and inflammatory conditions) as well as extra-articular structures (ligaments, muscles, etc.).