Prenatal exposure to opioids and neurodevelopment in infancy and childhood: A systematic review.

Aim: This systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies. Methods: We searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using "Covidence" systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment. Results: Data were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis. Conclusion: We explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.

Nonfatal opioid-related overdoses treated by emergency medical services in Florida, before and during the COVID-19 pandemic.

Previous studies have found increases in nonfatal opioid overdoses during the COVID-19 pandemic, which created difficult conditions for people with substance use disorders. We assessed changes in nonfatal opioid-related overdoses in Florida during the onset of the COVID-19 pandemic. Emergency medical service data was obtained from the Florida Department of Health. Naloxone administration with documented improvement was used as a proxy for nonfatal opioid-related overdoses. Age-adjusted rates were estimated per 100,000 population for April-September 2020 (n = 9,377) and compared to the same time period during 2019 (n = 6,765) using rate ratios. Age-adjusted rates were estimated by sex, race/ethnicity, and metro/nonmetro county classification, as well as county-level measures of medications for opioid use disorder (MOUD) availability, rates of COVID-19 deaths, and unemployment during 2020. The age-adjusted rate of nonfatal opioid-related overdoses increased from 32.41 (95 % CL: 31.64-33.19) during 2019 to 45.35 (95 % CL: 44.42-46.27) during 2020 (RR = 1.40; 95 % CL: 1.36-1.44). The rate for males increased most in metro counties (RR = 1.47, 95 % CL: 1.41-1.53); the rate for females increased most in nonmetro counties (RR = 1.51, 95 % CL: 1.10-2.06). The largest increases were observed among Hispanics (males: RR = 1.56, 95 % CL: 1.37-1.78; females: RR = 1.44, 95 % CL: 1.14-1.81), counties with no MOUD treatment options (RR = 1.66, 95 % CL: 1.14-2.44) and counties with the lowest rates of buprenorphine prescribers (RR = 1.70, 95 % CL: 1.29-2.22). Nonfatal opioid-related overdoses increased in Florida during the first six months of the COVID-19 pandemic. Expanding access to services that support treatment and recovery is critical to addressing the ongoing opioid crisis in Florida.

Defining and supporting high-quality telehealth for patients with opioid use disorder: The promise and potential pitfalls of telehealth expansion.

Many patients with opioid use disorders do not receive evidence-based treatment. The COVID-19 pandemic expanded the use of telehealth for prescribing medications for opioid use disorder (OUD). The uptake of telehealth has been variable, and this uneven expansion has created natural experiments to test assumptions and answer key questions about what improves outcomes for patients with OUD. Many current quality of care measures are not patient centered and do not focus on the practical questions that clinicians face. What criteria should be met before prescribing buprenorphine? Are physical exams necessary? Does the frequency and type of drug testing predict clinical outcomes? Are short check-in visits by phone or video better than less frequent in-person visits? Answering these questions can help define the essential components of high-quality care for patients with OUD. Defining the features of high-quality care can help create guardrails that will help protect our patients from potentially exploitive and ineffective care. Telehealth will likely end up being one additional tool to deliver care, but the scientific questions that can be answered during this period of rapid change can help answer some of the fundamental questions about providing high-quality care-and that will help all our patients, no matter how care is delivered.

Impact of the COVID-19 pandemic on opioid overdose and other adverse events in the USA and Canada: a systematic review.

IMPORTANCE: The COVID-19 pandemic impacted healthcare beyond COVID-19 infections. A better understanding of how COVID-19 worsened the opioid crisis has potential to inform future response efforts. OBJECTIVE: To summarize changes from the COVID-19 pandemic on outcomes regarding opioid use and misuse in the USA and Canada. EVIDENCE REVIEW: We searched MEDLINE via PubMed, EMBASE, and CENTRAL for peer-reviewed articles published between March 2020 and December 2021 that examined outcomes relevant to patients with opioid use, misuse, and opioid use disorder by comparing the period before vs after COVID-19 onset in the USA and Canada. Two reviewers independently screened studies, extracted data, assessed methodological quality and bias via Newcastle-Ottawa Scale, and synthesized results. FINDINGS: Among 20 included studies, 13 (65%) analyzed service utilization, 6 (30%) analyzed urine drug testing results, and 2 (10%) analyzed naloxone dispensation. Opioid-related emergency medicine utilization increased in most studies (85%, 11/13) for both service calls (17% to 61%) and emergency department visits (42% to 122%). Urine drug testing positivity results increased in all studies (100%, 6/6) for fentanyl (34% to 138%), most (80%, 4/5) studies for heroin (-12% to 62%), and most (75%, 3/4) studies for oxycodone (0% to 44%). Naloxone dispensation was unchanged and decreased in one study each. INTERPRETATION: Significant increases in surrogate measures of the opioid crisis coincided with the onset of COVID-19. These findings serve as a call to action to redouble prevention, treatment, and harm reduction efforts for the opioid crisis as the pandemic evolves. PROSPERO REGISTRATION NUMBER: CRD42021236464.

Differences in the delivery of medications for opioid use disorder during hospitalization by racial categories: A retrospective cohort analysis.

Background: As the drug-related overdose crisis and COVID-19 pandemic continue, communities need increased access to medications for opioid use disorder (MOUD) (i.e., buprenorphine and methadone). Disparities in the type of MOUD prescribed or administered by racial and ethnic categories are well described in the outpatient clinical environment. It is unknown, however, if these disparities persist when MOUD is provided in acute care hospitals. Methods: This study assessed differences in the delivery of buprenorphine versus methadone during acute medical or surgical hospitalizations for veterans with opioid use disorder (OUD) by racial categories (Black Non-Hispanic or Latino vs. White Non-Hispanic or Latino). Data were obtained retrospectively from the Veterans Health Administration (VHA) for federal fiscal year 2017. We built logistic regression models, adjusted for individual and hospital-related covariates, and calculated the predicted probabilities of MOUD delivery by racial categories. Results: The study cohort (n = 1,313 unique patients; N = 107 VHA hospitals) had a mean age of 57 (range 23 to 87 years), was predominantly male (96%), and composed entirely of Black (29%) or White (71%) patients. White patients were 11% more likely than Black patients to receive buprenorphine than methadone during hospitalization (p = 0.010; 95% CI: 2.7%, 20.0%). Among patients on MOUD prior to hospitalization, White patients were 21% more likely than Black patients to receive buprenorphine (p = 0.000; 95% CI: 9.8%, 31.5%). Among patients newly initiated on MOUD during hospitalization, there were no differences by racial categories. Conclusion: We observed disparities in the delivery of buprenorphine versus methadone during hospitalization by racial categories. The observed differences in hospital-based MOUD delivery may be influenced by MOUD received prior to hospitalization within the racialized outpatient addiction treatment system. The VHA and health systems more broadly must address all aspects of racism that contribute to inequitable MOUD access throughout all clinical contexts.

Pain Management and Opioid Therapy: Persistent Knowledge Gaps Among Primary Care Providers.

INTRODUCTION: Given the opioid epidemic in the US, it is vital that clinicians who prescribe opioids for pain management to do so in an evidence-based manner, eg considering all pharmacologic and non-pharmacologic options, assessing risk of opioid use disorder prior to initiating opioids. Continuing education regarding the evidence-based prescribing of opioids is now required for US healthcare providers who prescribe opioids. A "blueprint" of the content to be included in continuing education programs was developed by the US Food and Drug Administration and updated in 2018. METHODS: To understand the baseline knowledge and confidence of healthcare professionals in prescribing opioids for pain management, we posed 27 unique knowledge-based questions and 1 confidence question to clinician participants before or during 2 continuing educational programs that were based respectively on the 2016 and 2018 FDA Risk Evaluation and Mitigation Strategy (REMS) educational blueprints for pain management. RESULTS: Overall, 5571 clinicians completed these programs, including 1925 physicians (1516 [79%] identifying as primary care), 1181 physician assistants, 737 advanced practice nurses, 719 nurses, and 479 pharmacists. Responses to pretest questions in both programs indicated profound and persistent gaps in knowledge, particularly in definitions and mechanisms of pain, general principles of pharmacologic analgesic therapy, and specific aspects of opioid analgesic therapy and addiction. Participants in both programs also expressed limited confidence in their abilities to incorporate patient engagement techniques into pain management or develop a treatment plan for a patient with chronic pain. DISCUSSION: These data support an ongoing need for comprehensive clinician-based education as outlined in the FDA REMS educational blueprint, especially given recent data of escalating overdose deaths during the COVID-19 pandemic.

Impact of a tiered discharge opioid algorithm on prescriptions and patient-reported outcomes after open gynecologic surgery.

OBJECTIVE: To compare discharge opioid refills, prescribed morphine equivalent dose and quantity, and longitudinal patient-reported outcomes before and after implementation of a tiered opioid prescribing algorithm among women undergoing open gynecologic surgery within an enhanced recovery after surgery program. METHODS: We compared opioid prescriptions, clinical outcomes, and patient-reported outcomes among 273 women. Post-discharge symptom burden was collected up to 42 days after discharge using the validated 27-item MD Anderson Symptom Inventory and analyzed using linear mixed effects models and Kaplan-Meier curves for symptom recovery. RESULTS: Among 113 pre-implementation and 160 post-implementation patients there was no difference in opioid refills (9.7% vs 11.3%, p=0.84). The post-implementation cohort had a significant reduction in median morphine equivalent dose (112.5 mg vs 225 mg, p<0.01), with no difference in median hospital length of stay (3 days vs 3 days, p=1.0) or 30-day readmission rate (9.4% vs 7.1%, p=0.66). There was no difference in patient-reported pain between the pre- and post-implementation cohorts on the day of discharge (severity 4.93 vs 5.14, p=0.53) or in any patient-reported symptoms, interference measures, or composite scores by post-discharge day 7. The median recovery time for most symptoms was 7 days, except for pain (14 days), fatigue (18 days), and physical interference (21 days), with no differences between cohorts. CONCLUSIONS: After implementation of a tiered opioid prescribing algorithm, the quantity and dose of discharge opioids prescribed decreased with no change in post-operative refills and without negatively impacting patient-reported symptom burden or interference, which can be used to educate and reassure patients and providers.

Buprenorphine management in the perioperative period: educational review and recommendations from a multisociety expert panel.

BACKGROUND: The past two decades have witnessed an epidemic of opioid use disorder (OUD) in the USA, resulting in catastrophic loss of life secondary to opioid overdoses. Medication treatment of opioid use disorder (MOUD) is effective, yet barriers to care continue to result in a large proportion of untreated individuals. Optimal analgesia can be obtained in patients with MOUD within the perioperative period. Anesthesiologists and pain physicians can recommend and consider initiating MOUD in patients with suspected OUD at the point of care; this can serve as a bridge to comprehensive treatment and ultimately save lives. METHODS: The Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, American Society of Anesthesiologists, American Academy of Pain Medicine, American Society of Addiction Medicine and American Society of Health System Pharmacists approved the creation of a Multisociety Working Group on Opioid Use Disorder, representing the fields of pain medicine, addiction, and pharmacy health sciences. An extensive literature search was performed by members of the working group. Multiple study types were included and reviewed for quality. A modified Delphi process was used to assess the literature and expert opinion for each topic, with 100% consensus being achieved on the statements and each recommendation. The consensus statements were then graded by the committee members using the United States Preventive Services Task Force grading of evidence guidelines. In addition to the consensus recommendations, a narrative overview of buprenorphine, including pharmacology and legal statutes, was performed. RESULTS: Two core topics were identified for the development of recommendations with >75% consensus as the goal for consensus; however, the working group achieved 100% consensus on both topics. Specific topics included (1) providing recommendations to aid physicians in the management of patients receiving buprenorphine for MOUD in the perioperative setting and (2) providing recommendations to aid physicians in the initiation of buprenorphine in patients with suspected OUD in the perioperative setting. CONCLUSIONS: To decrease the risk of OUD recurrence, buprenorphine should not be routinely discontinued in the perioperative setting. Buprenorphine can be initiated in untreated patients with OUD and acute pain in the perioperative setting to decrease the risk of opioid recurrence and death from overdose.

COVID-19-related policy changes for methadone take-home dosing: A multistate survey of opioid treatment program leadership.

Background: In the United States, methadone for treatment of opioid use disorder is dispensed via highly-regulated accredited opioid treatment programs (OTP). During the COVID-19 pandemic, federal regulations were loosened, allowing for greater use of take-home methadone doses. We sought to understand how OTP leaders responded to these policy changes. Methods: We distributed a multistate electronic survey from September to November 2020 of OTP leadership to members of the American Association for the Treatment of Opioid Dependence (AATOD) who self-identified as leaders of OTPs. We asked study participants about how their OTP(s) implemented COVID-19-related policy changes into their clinical practice focusing on provision of take-home methadone doses, factors used to determine patient stability, and potential concerns about increased take-home doses. We used Chi-square test to compare survey responses between characterizations of the OTPs. Results: Of 170 survey respondents (17% response rate), the majority represented leadership of for-profit OTPs (69%) and were in a Southern state (54%). Routine allowances and practices related to take-home methadone doses varied across OTPs during the COVID-19 pandemic: 80 (47%) reported 14 days for newly enrolled patients (within past 90 days), 89 (52%) reported 14 days for "less stable" patients, and 112 (66%) reported 28 days for "stable" patients. Conclusions: We found that not all eligible OTP leaders adopted the practice of routinely allowing newly enrolled, "less stable," and "stable" patients on methadone to have increased take-home doses up to the limit allowed by federal regulations during COVID-19. The pandemic provides an opportunity to critically re-evaluate long-established methadone and OTP regulations in preparation for future emergencies.

COVID-19: A new barrier to treatment for opioid use disorder in the emergency department.

OBJECTIVE: Start Treatment and Recover (STAR) is an emergency department (ED) program that expands access to medication for opioid use disorder by identifying patients with opioid use disorder and offering ED-initiated buprenorphine/naloxone and rapid access to outpatient treatment. We sought to determine the impacts of the coronavirus disease 2019 pandemic on STAR and the patients with opioid use disorder it serves. METHODS: We conducted a retrospective review of records comparing 2 periods: pre-pandemic (February 1, 2019-February 29, 2020) and pandemic (March 1, 2020-May 31, 2020). Variables evaluated included the number of STAR enrollments, ED census, percentage of census screening positive for opioid use disorder, number and percentage of ED overdose visits, and overdose fatalities by month. All analyses were conducted using 2-sample t tests to calculate the mean and 95% confidence intervals (CIs). RESULTS: Comparing the pre-pandemic to the pandemic period, the mean monthly ED visits decreased from 5126.9 to 3306.7 (difference = -1820.3; 95% CI, -3406.3 to -234.2), STAR mean monthly enrollments decreased from 9.7 to 1.3 (difference = -8.4; 95% CI, -12.8 to -4.0), and statewide monthly opioid-related fatalities increased from 9.4 to 15.3 (difference = 5.9; 95% CI, 0.8 to 11.1). However, the percentage of individuals who presented to the ED with opioid use disorder or overdose remained unchanged. CONCLUSION: Although overall ED visits declined during the pandemic period, the percentage of patients presenting with opioid use disorder or overdose remained constant, yet there was a dramatic decline in enrollment in ED-initiated medication for opioid use disorder and an increase in statewide monthly opioid-related fatalities. Strategies to maintain medication for opioid use disorder treatment options must be implemented for this vulnerable population during the ongoing pandemic.

Harm Reduction for Adolescents and Young Adults During the COVID-19 Pandemic: A Case Study of Community Care in Reach.

The coronavirus disease 2019 (COVID-19) pandemic has challenged the ability of harm reduction programs to provide vital services to adolescents, young adults, and people who use drugs, thereby increasing the risk of overdose, infection, withdrawal, and other complications of drug use. To evaluate the effect of the COVID-19 pandemic on harm reduction services for adolescents and young adults in Boston, we conducted a quantitative assessment of the Community Care in Reach (CCIR) youth pilot program to determine gaps in services created by its closure during the peak of the pandemic (March 19-June 21, 2020). We also conducted semistructured interviews with staff members at 6 harm reduction programs in Boston from April 27 through May 4, 2020, to identify gaps in harm reduction services, changes in substance use practices and patterns of engagement with people who use drugs, and how harm reduction programs adapted to pandemic conditions. During the pandemic, harm reduction programs struggled to maintain staffing, supplies, infection control measures, and regular connection with their participants. During the 3-month suspension of CCIR mobile van services, CCIR missed an estimated 363 contacts, 169 units of naloxone distributed, and 402 syringes distributed. Based on our findings, we propose the following recommendations for sustaining harm reduction services during times of crisis: pursuing high-level policy changes to eliminate political barriers to care and fund harm reduction efforts; enabling and empowering harm reduction programs to innovatively and safely distribute vital resources and build community during a crisis; and providing comprehensive support to people to minimize drug-related harms.

Leveraging pharmacists to maintain and extend buprenorphine supply for opioid use disorder amid COVID-19 pandemic.

PURPOSE: Strategies for deploying clinical pharmacists to increase access to buprenorphine in inpatient, outpatient and transitional care, and community practice settings are described. SUMMARY: Access to medications for opioid use disorder (MOUD) is essential, but patients face many barriers when pursuing treatment and MOUD. The coronavirus disease 2019 (COVID-19) pandemic has compounded the opioid crisis and worsened outcomes by introducing new barriers to MOUD access. Many strategies to ensure continued access to MOUD have been described, but the role of leveraging pharmacists during the opioid/COVID-19 syndemic to improve medication access and outcomes remains underappreciated. Pharmacists, while both qualified and capable of liberalizing access to all forms of MOUD, may have the strongest impact by increasing access to buprenorphine. Herein, we present progressive strategies to maintain and extend buprenorphine access for patients with OUD through deployment of clinical pharmacists, particularly in the context of the COVID-19 pandemic, during which access may be further restricted. CONCLUSION: Leveraging pharmacists to extend access to MOUD, particularly buprenorphine, remains an underutilized strategy that should be implemented, particularly during the concurrent COVID-19 global pandemic.

Sharp decline in hospital and emergency department initiated buprenorphine for opioid use disorder during COVID-19 state of emergency in California.

The California Bridge Program supports expansion of medications for opioid use disorder (MOUD) in emergency departments (EDs) and hospital inpatient units across the state. Here, we describe the change in activity before and after the coronavirus disease 2019 (COVID-19) California statewide shutdown. Of the 70 participating hospitals regionally distributed across California, 52 report MOUD-related activity monthly. We analyzed data on outcomes of OUD care and treatment: identification of OUD, acceptance of referral, receipt of buprenorphine prescription, administration of buprenorphine, and follow-up linkage to outpatient OUD treatment, from May 2019 to April 2020. In estimating the expected number of patients who met each outcome in April 2020, we found decreases in the expected to observed number of patients across all outcomes (all p-values<0.002): 37% (from 1053 to 667) decrease in the number of patients identified with OUD, 34% (from 632 to 420) decrease in the number of patients who accepted a referral, 48% (from 521 to 272) decrease in the number of patients who were prescribed buprenorphine, 53% (from 501 to 234) decrease in the number of patients who were administered buprenorphine, and 33% (from 416 to 277) decrease in the number of patients who attended at least one follow-up visit for addiction treatment. The COVID-19 California statewide shutdown was associated with an abrupt and large decrease in the progress toward expanded access to OUD treatment.