Comparison of opioid use disorder patients with and without problematic internet use in terms of impulsivity and attention deficit hyperactivity disorder.

OBJECTIVE: To investigate attention deficit and hyperactivity disorder (ADHD) symptoms and impulsivity among individuals diagnosed with opioid use disorder (OUD) who also exhibit symptoms of problematic internet use (PIU). METHODS: The study involved the participation of 360 patients with OUD enrolled at an alcohol and drug addiction treatment center (ADATC) from October to December 2022. Various assessment tools were administered, including Young's Internet Addiction Scale (YIAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS), and Adult ADHD Self-Report Scale (ASRS). PIU was identified by YIAS scores equal to or exceeding 50. RESULTS: Most participants diagnosed with OUD had comorbid PIU, with high levels of depression, anxiety, and ADHD symptoms. Both BDI and BAI scores were significantly increased in the PIU group compared to the non-PIU group (p < 0.001). Significant differences were observed in BIS Motor Impulsivity, Attentional Impulsivity, and total scores, indicating higher impulsivity in the PIU group (all p < 0.001). Additionally, higher ASRS scores were found in the PIU group (p < 0.001). CONCLUSION: These findings highlight the importance of addressing PIU and comorbidities in OUD treatment. Interventions targeting ADHD symptoms and emotional well-being may benefit PIU management.

Comparison of opioid use disorder patients with and without problematic internet use in terms of impulsivity and attention deficit hyperactivity disorder

Objective: To investigate attention deficit and hyperactivity disorder (ADHD) symptoms and impulsivity among individuals diagnosed with opioid use disorder (OUD) who also exhibit symptoms of problematic internet use (PIU). Methods: The study involved the participation of 360 patients with OUD enrolled at an alcohol and drug addiction treatment center (ADATC) from October to December 2022. Various assessment tools were administered, including Young's Internet Addiction Scale (YIAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS), and Adult ADHD Self-Report Scale (ASRS). PIU was identified by YIAS scores equal to or exceeding 50. Results: Most participants diagnosed with OUD had comorbid PIU, with high levels of depression, anxiety, and ADHD symptoms. Both BDI and BAI scores were significantly increased in the PIU group compared to the non-PIU group (p < 0.001). Significant differences were observed in BIS Motor Impulsivity, Attentional Impulsivity, and total scores, indicating higher impulsivity in the PIU group (all p < 0.001). Additionally, higher ASRS scores were found in the PIU group (p < 0.001). Conclusion: These findings highlight the importance of addressing PIU and comorbidities in OUD treatment. Interventions targeting ADHD symptoms and emotional well-being may benefit PIU management.

A Dyadic Framework of Care for Opioid-exposed Birthing Persons and Their Infants and Children.

OBJECTIVE: To develop a dyadic-centered framework focused on clinical care, surveillance, and research for birthing persons with opioid use disorder (OUD) and their infants and children. STUDY DESIGN: Between February and March 2023, an analysis was conducted within the US Department of Health and Human Services (HHS) of activities directed at opioid-exposed birthing persons and their infants and children (the dyad) to identify: 1) number of activities, stratified by type and 2) characteristics across health and supportive activities that serve the dyad vs birthing persons or infants and children individually. Descriptive and thematic analyses were used to assess quantity and characteristics of fiscal year 2023-2024 activities aggregated across eleven HHS agencies. RESULTS: Of 181 activities examined, 75 met inclusion criteria specific to serving birthing persons with OUD and opioid-exposed infants and children. Sixty-two percent of activities were dyad focused. Five categories of dyadic activities were identified: research (45%), education and training (28%), health and supportive services (21%), surveillance (4%), and quality improvement (2%). Eight specific characteristics were key to dyadic activities: a life course and generational approach, emphasis on relationship, dyadic outcomes, service wraparound, payment structures supporting dyadic care, data linkage, and social determinants of health. CONCLUSIONS: This analysis of HHS activities directed at birthing persons with OUD and opioid-exposed infants and children showed that most programs had a dyadic focus. Synthesizing elements identified from activities serving the dyad facilitated the development of a dyadic framework integrating clinical care, public health surveillance, and research.

Association of opioid use disorder with outcomes of hospitalizations for acute myocardial infarction in the United States.

OBJECTIVE: While Opioid Use Disorder (OUD) has been linked to inferior clinical outcomes, studies examining the clinical outcomes and readmission of OUD patients experiencing Acute Myocardial Infarction (AMI) remain lacking. The authors analyze the clinical and financial outcomes of OUD in a contemporary cohort of AMI hospitalizations. METHODS: All non-elective adult (≥ 18 years) hospitalizations for AMI were tabulated from the 2016‒2019 Nationwide Readmissions Database using relevant International Classification of Disease codes. Patients were grouped into OUD and non-OUD cohorts. Bivariate and regression analyses were performed to identify the independent association of OUD with outcomes after non-elective admission for AMI, as well as subsequent readmission. RESULTS: Of an estimated 3,318,257 hospitalizations for AMI meeting study criteria, 36,057 (1.1%) had a concomitant diagnosis of OUD. While OUD was not significantly associated with mortality, OUD patients experienced superior cardiovascular outcomes compared to non-OUD. However, OUD was linked to increased odds of non-cardiovascular complications, length of stay, costs, non-home discharge, and 30-day non-elective readmission. CONCLUSIONS: Patients with OUD presented with AMI at a significantly younger age than non-OUD. While OUD appears to have a cardioprotective effect, it is associated with several markers of increased resource use, including readmission. The present findings underscore the need for a multifaceted approach to increasing social services and treatment for OUD at index hospitalization.

Cannabinoids for Substance Use Disorder Treatment: What Does the Current Evidence Say?

Background: The prevalence of Substance Use Disorder (SUD) is increasing along with the need to develop approaches to reduce the harm associated with substance use, including investigating alternatives such as cannabinoids, which show promising results, although the current evidence is limited. This scoping review focuses on the limitations and potentials of cannabinoid-based treatments for SUDs. Methods: We examined between-subject randomized controlled trials (RCTs) investigating the use of CBD and THC as pharmacological treatment for SUDs in adults, with the procedures attending the expectations of the Preferred Reporting Items for Scoping reviews and Meta-Analyses (PRISMA) for Scoping Reviews guidelines and assessed risk of bias using the Cochrane Risk of Bias Assessment Tool 2. Results: Ten RCTs were included, with six demonstrating low risk of bias, and positive results were found for treating Cannabis Use Disorder, while contradictory results were found for Opioid Use Disorder, and inconclusive results for treating Cocaine Use Disorder. Conclusions: CBD and THC demonstrate potential for treating some SUDs, but evidence is limited. Robust RCTs with larger samples and longer follow-up periods are necessary to assess carefully developed outcomes for different SUD patients. New cannabinoid-based medications and scientific-based policies may advance SUD treatment. A comprehensive approach to treatment and careful methodological choices may benefit patients with SUD.

Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes.

OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n = 1986), primarily using no substances; licit use (6.6%; n = 145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n = 64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P = .001, d = .64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P < .001, d = .16). CONCLUSIONS: The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles.

Screening for opioid use disorder and co-occurring depression and post-traumatic stress disorder in primary care in New Mexico.

BACKGROUND: Identifying patients in primary care services with opioid use disorder and co-occurring mental health disorders is critical to providing treatment. Objectives of this study were to (1) assess the feasibility of recruiting people to screen in-person for opioid use disorder and co-occurring mental health disorders (depression and/or post-traumatic stress disorder) in primary care clinic waiting rooms in preparation for a randomized controlled trial, and (2) compare results of detecting these disorders by universal in-person screening compared to electronic health record (EHR) diagnoses. METHODS: This cross-sectional feasibility and pilot study recruited participants from four primary care clinics, two rural and two urban, from three health care organizations in New Mexico. Inclusion criteria were adults (≥ 18 years), attending one of the four clinics as a patient, and who spoke English or Spanish. Exclusion criteria were people attending the clinic for a non-primary care visit (e.g., dental, prescription pick up, social support). The main outcomes and measures were (1) recruitment feasibility which was assessed by frequencies and proportions of people approached and consented for in-person screening, and (2) relative differences of detecting opioid use disorder and co-occurring mental health disorders in waiting rooms relative to aggregate EHR data from each clinic, measured by prevalence and prevalence ratios. RESULTS: Over two-weeks, 1478 potential participants were approached and 1145 were consented and screened (77.5% of patients approached). Probable opioid use disorder and co-occurring mental health disorders were identified in 2.4% of those screened compared to 0.8% in EHR. Similarly, universal screening relative to EHR identified higher proportions of probable opioid use disorder (4.5% vs. 3.4%), depression (17.5% vs. 12.7%) and post-traumatic stress disorder (19.0% vs. 3.6%). CONCLUSIONS: Universal screening for opioid use disorder, depression, and post-traumatic stress disorder was feasible, and identified three times as many patients with these co-occurring disorders compared to EHR. Higher proportions of each condition were also identified, especially post-traumatic stress disorder. Results support that there are likely gaps in identification of these disorders in primary care services and demonstrate the need to better address the persistent public health problem of these co-occurring disorders.

Within subject cross-tissue analyzes of epigenetic clocks in substance use disorder postmortem brain and blood.

There is a possible accelerated biological aging in patients with substance use disorders (SUD). The evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Consequently, the impact of biological aging in the brain of individuals with SUD remains unknown. In this study, we evaluated multiple epigenetic clocks (DNAmAge, DNAmAgeHannum, DNAmAgeSkinBlood, DNAmPhenoAge, DNAmGrimAge, and DNAmTL) in individuals with SUD (n = 42), including alcohol (n = 10), opioid (n = 19), and stimulant use disorder (n = 13), and controls (n = 10) in postmortem brain (prefrontal cortex) and blood tissue obtained from the same individuals. We found a higher DNAmPhenoAge (ß = 0.191, p-value = 0.0104) and a nominally lower DNAmTL (ß = -0.149, p-value = 0.0603) in blood from individuals with SUD compared to controls. SUD subgroup analysis showed a nominally lower brain DNAmTL in subjects with alcohol use disorder, compared to stimulant use disorder and controls (ß = 0.0150, p-value = 0.087). Cross-tissue analyzes indicated a lower blood DNAmTL and a higher blood DNAmAge compared to their respective brain values in the SUD group. This study highlights the relevance of tissue specificity in biological aging studies and suggests that peripheral measures of epigenetic clocks in SUD may depend on the specific type of drug used.

Association of opioid use disorder with outcomes of hospitalizations for acute myocardial infarction in the United States

Abstract Objective While Opioid Use Disorder (OUD) has been linked to inferior clinical outcomes, studies examining the clinical outcomes and readmission of OUD patients experiencing Acute Myocardial Infarction (AMI) remain lacking. The authors analyze the clinical and financial outcomes of OUD in a contemporary cohort of AMI hospitalizations. Methods All non-elective adult (≥ 18 years) hospitalizations for AMI were tabulated from the 2016‒2019 Nationwide Readmissions Database using relevant International Classification of Disease codes. Patients were grouped into OUD and non-OUD cohorts. Bivariate and regression analyses were performed to identify the independent association of OUD with outcomes after non-elective admission for AMI, as well as subsequent readmission. Results Of an estimated 3,318,257 hospitalizations for AMI meeting study criteria, 36,057 (1.1%) had a concomitant diagnosis of OUD. While OUD was not significantly associated with mortality, OUD patients experienced superior cardiovascular outcomes compared to non-OUD. However, OUD was linked to increased odds of non-cardiovascular complications, length of stay, costs, non-home discharge, and 30-day non-elective readmission. Conclusions Patients with OUD presented with AMI at a significantly younger age than non-OUD. While OUD appears to have a cardioprotective effect, it is associated with several markers of increased resource use, including readmission. The present findings underscore the need for a multifaceted approach to increasing social services and treatment for OUD at index hospitalization.

Nursing Resources Linked to Postsurgical Outcomes for Patients With Opioid Use Disorder: An Observational Study.

To determine whether better nursing resources (ie, nurse education, staffing, work environment) are each associated with improved postsurgical outcomes for patients with opioid use disorder (OUD). Background: Hospitalized patients with OUD are at increased risk of adverse outcomes. Evidence suggests that adverse postsurgical outcomes may be mitigated in hospitals with better nursing resources, but this has not been evaluated among surgical patients with OUD. Methods: Cross-sectional (2015-2016) data were utilized from the RN4CAST-US survey of hospital nurses, the American Hospital Association Annual Survey of hospitals, and state patient hospital discharge summaries. Multivariate logistic and zero-truncated negative binomial regression models were employed to examine the association between nursing resources and 30-day readmission, 30-day in-hospital mortality, and length of stay for surgical patients with OUD. Results: Of 919,601 surgical patients in 448 hospitals, 11,610 had identifiable OUD. Patients with compared to without OUD were younger and more often insured by Medicaid. Better nurse education, staffing, and work environment were each associated with better outcomes for all surgical patients. For patients with OUD, each 10% increase in the proportion of nurses with a bachelor's degree in nursing was associated with even lower odds of 30-day readmission (odds ratio [OR] = 0.88; P = 0.001), and each additional patient-per-nurse was associated with even lower odds of 30-day readmission (OR = 1.09; P = 0.024). Conclusions: All surgical patients fare better when cared for in hospitals with better nursing resources. The benefits of having more nurses with a bachelor's degree and fewer patients-per-nurse in hospitals appear greater for surgical patients with OUD.

Association of co-occurring mental health problems with hepatitis C status among young people who inject drugs in rural New Mexico, 2016-2018.

BACKGROUND: Injection drug use (IDU) remains the strongest risk factor for hepatitis C virus (HCV) in the United States. HCV rates are increasing in rural areas among young adult people who inject drugs (PWID). People with HCV and PWID have disproportionate rates of mental health problems; however, it is unclear whether risky injection behaviors mediate the association between mental health problems and HCV. We examined the association between mental health problems and HCV in a rural cohort of young adult PWID, with the goal of informing rural service delivery. METHODS: We conducted a secondary analysis of cross-sectional data from a convenience sample of young adult PWID in 2 rural counties in New Mexico. Participants were recruited from 2 community venues between September 2016 and May 2018. Associations between mental health problems and HCV were examined using bivariate (Fisher's exact) and multivariable modified Poisson regression analyses (with robust standard errors). Using structural equation modeling (SEM), we assessed duration of IDU and receptive syringe sharing (RSS) as mediators of this relationship. RESULTS: A total of 263 patients were enrolled, with a median age of 26.1 years. The majority were male (66.3%) and Hispanic/Latino (a) (87.6%). The median age first injected was 19 years, and over half reported having ever engaged in RSS (53.4%). At least one mental health problem was reported by 60.1% of participants, with post-traumatic stress disorder (PTSD) being the most prevalent condition (42.2%). A majority (60.9%) tested positive for HCV antibody, and just under half (45.7%) of all participants tested positive for HCV ribonucleic acid. In SEM, PTSD had a significant total effect on HCV (τ = 0.230, P = 0.05), and this relationship was partially mediated by duration of IDU (αß = 0.077, P = 0.03). The association between mental health problems and HCV was partially mediated by duration of IDU and the sequential mediation of duration of IDU and RSS (αß + αßß = 0.091, P = 0.05). CONCLUSIONS: High HCV rates among young adult PWID in rural New Mexico may be partly explained by mental health problems, duration of IDU and RSS. Mental health services for young adult PWID in rural areas may help decrease HCV transmission in rural areas. Trial Registration N/A.

Risk of Suicide in Patients With Major Depressive Disorder and Comorbid Chronic Pain Disorder: An Insight From National Inpatient Sample Data.

BACKGROUND: Approximately 17.3 million adults in the United States have had a minimum of one major depressive episode. Comorbidity of depression and pain can affect individuals of any age, but is more prevalent in the elderly affecting up to 13% of people in the elderly population. Given that depression and suicidal ideation (SI) pose a considerable burden resulting in enormous suffering, there is a need to understand the factors of the relationship between chronic pain (CP), depression, and SI. OBJECTIVES: Our primary objective in this study was to compare suicidality (SI/attempt [SA]) between patients with major depressive disorder (MDD) and CP and a matched control group. The secondary objective was to compare length of stay, total hospital costs, and discharge disposition in these populations. STUDY DESIGN: The National Inpatient Sample (NIS) dataset developed by the Healthcare Cost and Utilization Project was used for this study. The NIS is a database of hospital inpatient stays derived from billing data submitted by hospitals to statewide data organizations across the United States. We obtained patient records from the NIS dataset for the years 2006 to 2017. All data were de-identified so Institutional Review Board approval was waived. METHODS: We used mean and standard error to describe continuous data and counts (percentage) to describe categorical data. Categorical data were compared using Rao-Scott adjusted chi-square tests and continuous data were compared using Student's t tests. Matching was performed using propensity scores in random order with a caliper size of 0.001. To assess predictors associated with suicidality, logistic regression analysis was performed. RESULTS: A total of 393,481 patients having MDD with CP (MDD+CP) were included in the analysis. The mean age was 49.4 years, and 54.9% of patients were women. Overall, rate of composite outcome of SI/SA was more prevalent in MDD+CP group (51% vs 41%, P < 0.001). Rate of SI was 48% vs 39% (P < 0.001) in the MDD+CP and MDD without CP (MDD-CP) groups, respectively. MDD+CP was one of the strongest predictors of suicidality, responsible for 48% more risk of SI/SA compared to MDD-CP group. In comparison to non-Whites, the rate of suicidality was 7.5% less in White population. Alcohol abuse and substance abuse were associated with 17% and 8% greater risk of SI/SA, respectively. For women, the odds of having SI/SA was 1.20 greater compared to men. LIMITATIONS: No information was available on the causal relationship between MDD+CP disorder and SI/SA. Retrospective studies are susceptible to recognition, reporting, and coding bias. There is no information available on medications use or the duration and severity of CP and bipolar disorder, which can all be confounding factors. CONCLUSIONS: Psychiatrists and other physicians must be cognizant of the presence of CP and the risk of suicide, especially when patients present with depressive symptoms. The treatment plan for this patient population should include routine screening for pain symptoms and risk assessment for SI.

Prevalence of Chronic Opioid Use in the Elderly After Hip Fracture Surgery.

BACKGROUND: While interest has focused on opioid use after total hip arthroplasty, little research has investigated opioid use in elderly patients after hip fracture. We hypothesize that a substantial number of opioid-naïve elderly patients go on to chronic opioid use after hip fracture surgery. METHODS: We reviewed a consecutive series of 219 patients 65 years and older who underwent surgical fixation between January 1, 2016 and February 28, 2019 for a native hip fracture. Patients were excluded for polytrauma, periprosthetic or pathologic fractures, recent major surgery, or death within 90 days of their hip surgery. The state prescription monitoring database was used to determine opioid use. RESULTS: Overall, 58 patients (26%) were postoperative chronic opioid users. Of the initial 188 opioid-naïve patients, 43 (23%) became chronic users. Of the 31 preoperative opioid users, 15 (48%) continued as chronic users. Chronic postoperative users were more likely to be White (76% vs 91%, P = .04), younger (78 vs 82 years, P = .003), and preoperative opioid users (odds ratio 3.3, P = .007). Arthroplasty vs fixation did not affect the rate of chronic opioid use (P = .22). CONCLUSION: Chronic opioid use is surprisingly common after hip fracture repair in the elderly. Twenty-three percent of opioid-naïve hip fracture patients became chronic users after surgery. Continued vigilance is needed by orthopedic surgeons to limit the amount and duration of postoperative narcotic prescriptions and to monitor for continued use.

Experiences and Preferences of Opioid-Use-Disorder Patients Who Switched from Brand to Generic Buprenorphine/Naloxone Films: A Case Series.

PURPOSE: Differences in the suppression of withdrawal symptoms have been observed in opioid-use-disorder (OUD) patients who were switched from Suboxone (the brand name of buprenorphine/naloxone sublingual films) to either 1 of 2 generic versions. These descriptive observations evidence the need to further assess the use of these generics and its impact on the adherence to and outcomes of OUD treatments. The objective of this case series was to describe patient and provider experiences, perceptions, and preferences when said patients were abruptly switched from Suboxone to one of the generic versions manufactured by Sandoz or Alvogen. PATIENTS AND METHODS: A retrospective chart review of 24 Suboxone-maintained OUD patients from a single clinic who were forced to switch to a generic was performed to collect withdrawal and craving symptoms that occurred after the switch, as well as toxicology results and changes in dose (documented by the provider). RESULTS: The medical records of 9 (37.5%) of the 24 patients showed that they were suffering from withdrawal symptoms and/or cravings, had had their doses adjusted, and/or had had a positive urine toxicology screen. All 9 subjects communicated a preference for the brand formulation over that of either of the generic versions; few expressed a preference for one generic formulation over the other. None of patients were able to switch back to the brand formulation, nor were any of them able to choose the generic that worked best for them. Insomnia, muscle pain, and gooseflesh skin were the most common withdrawal symptoms reported by the patients using the generics. Better outcomes were observed in patients who received a buprenorphine dose increase (2 mg) to suppress the withdrawal symptoms experienced while using the generics. CONCLUSION: Our study serves as a reference to prescribers regarding approaches (eg, a small dose adjustment) that may potentially encourage OUD treatment adherence and even improve outcomes in patients who appear to be decompensating after the brand-to-generic switch.

Promoting interprofessional student outcomes through the narrative of an opioid use disorder survivor.

The inappropriate use of opioids is a national concern. Experts suggest a multifaceted, collaborative practice approach to reduce mortality rates in complex healthcare issues is effective. Before practice, students require education to address the development of interprofessional (IP) skills. The purpose of this mixed-methods cohort study was to identify changes in student self-perceived value of IP socialization skills and to explore student perceptions of IP engagement in the context of the opioid crisis, before and after a combined IP panel and focus group discussion using a healthcare professional's journey from addiction into recovery. Thirty-three pre-licensure healthcare students in Schools of Counseling, Nursing, Occupational Therapy, Pharmacy, and Physical Therapy assessed their IP experience using the Interprofessional Socialization and Valuing Scale (ISVS). The IP event included interactive discussions with a panel of healthcare providers, a pharmacist in recovery from opioid use disorder, and a local prescription drug awareness and prevention advocate. Significant differences occurred between pre and post ISVS scores in the perceived value of IP collaborative work. Results from the qualitative analysis revealed a need for student-driven self-reflection before the discussions evolved to address the perspectives of future practitioner, the patient, and the healthcare system. Creating a real-time, face-to-face interaction with a panel of healthcare practitioners, an opioid survivor in concert with a local prescription drug prevention advocate may be an effective means toward improving teaching IP value and progressing student outcomes toward IP skill attainment.

Longitudinal Health Care Utilization of Medicaid-Insured Children with a History of Neonatal Abstinence Syndrome.

OBJECTIVE: To describe longitudinal health care utilization of Medicaid-insured children with a history of neonatal abstinence syndrome (NAS) compared with similar children without NAS. STUDY DESIGN: Retrospective, longitudinal cohort study. Data were extracted from the Medicaid Analytic eXtract files for all available states and DC from 2003-2013. Subjects were followed up to 11 years. In total, 17 229 children with NAS were identified using the International Classification of Diseases, Ninth Revision code 779.5. Children without NAS, matched on demographic and health variables, served as the comparison group. Outcomes were number of claims for inpatient, outpatient, and emergency department encounters, numbers of prescription claims, and costs associated with these services. Linked claims were identified for each subject using a unique, within-state ID. RESULTS: Children with NAS had increased claims for inpatient admissions (marginal effect [ME] 0.49; SE 0.01) and emergency department visits (ME 0.30; SE 0.04) through year 1; increased prescriptions (ME 1.45; SE 0.08, age 0) (ME 0.69; SE 0.11, age 1 year) through year 2; and increased outpatient encounters (ME 20.13; SE 0.54, age 0) (ME 3.95; SE 0.62, age 1 year) (ME 2.90; SE 1.11, age 2 years) through year 3 after adjusting for potential confounders (P < .01 for all). Beyond the third year, health care utilization was similar between those with and without NAS. CONCLUSIONS: Children with a diagnosis of NAS have greater health care utilization through the third year of life. These differences resolve by the fourth year. Our results suggest resolution of disparities may be due to shifts in developmental health management in school-age children and inability to track relevant diagnoses in a health care database.

Opioids in COVID-19: Two Sides of a Coin.

Introduction: The treatment of most severe COVID-19 patients included the large-scale use of sedatives and analgesics-possibly in higher doses than usual-which was reported in the literature. The use of drugs that decrease mortality is necessary and opioids are important agents in procedures such as orotracheal intubation. However, these drugs seem to have been overestimated in the COVID-19 pandemic. We performed a review of the PubMed-Medline database to evaluate the use of opioids during this period. The following descriptors were used to enhance the search for papers: "Opioids", "COVID-19," "COVID-19 pandemic," "SARS-CoV-2," "Opioid use disorder," "Opioid dependence" and the names of the drugs used. We also evaluated the distribution of COVID-19 patients in Brazil and the applicability of opioids in our country during the COVID-19 pandemic. Results: Several positive points were found in the use of opioids in the COVID-19 pandemic, for instance, they can be used for analgesia in orotracheal intubation, for chronic pain management, and as coadjutant in the management of acute intensification of pain. However, high doses of opioids might exacerbate the respiratory depression found in COVID-19 patients, their chronic use can trigger opioid tolerance and the higher doses used during the pandemic might result in greater adverse effects. Unfortunately, the pandemic also affected individuals with opioid use disorder, not only those individuals are at higher risk of mortality, hospitalization and need for ventilatory support, but measures taken to decrease the SARS-CoV-2 spread such as social isolation, might negatively affect the treatment for opioid use disorder. In Brazil, only morphine, remifentanil and fentanyl are available in the basic health care system for the treatment of COVID-19 patients. Out of the 5,273,598 opioid units used in this period all over the country, morphine, fentanyl, and remifentanil, accounted for, respectively, 559,270 (10.6%), 4,624,328 (87.6%), and 90,000 (1.8%) units. Many Brazilian regions with high number of confirmed cases of COVID-19 had few units of opioids available, as the Southeast region, with a 0.23 units of opioids per confirmed COVID-19 case, and the South region, with 0.05 units. In the COVID-19 pandemic scenario, positive points related to opioids were mainly the occurrence of analgesia, to facilitate intubation and their use as coadjutants in the management of acute intensification of pain, whereas the negative points were indiscriminate use, the presence of human immunosuppressor response and increased adverse effects due to higher doses of the drug. Conclusion: The importance of rational and individualized use of analgesic hypnotics and sedative anesthetics should be considered at all times, especially in situations of high demand such as the COVID-19 pandemic.

Brand-to-Generic Substitution of Buprenorphine/Naloxone Sublingual Film in Puerto Rico: A Case Study.

A 56-year-old patient with a 1-year history of stable maintenance treatment with Suboxone for opioid use disorder (OUD) was switched to a generic formulation in May of 2019. The patient reported experiencing-over the course of the following 3 months-withdrawal symptoms when switched to the Alvogen-produced generic formulation in May of 2019 and then to the Sandoz-produced version in July of that same year, she also was positive for fentanyl during that time. As a result, the buprenorphine dose was increased, and the patient was stable at this new dose using the generic versions. Blood levels pre- and post-change (not reported in previous case reports) showed maximum buprenorphine concentration being reached more quickly when the brand-name drug was used. Additionally, the area under the curve (AUC) values indicate that the generic formulation had higher exposures than the brand-name drug. Based on the clinical impact of the brand-to generic switch in this patient, further research in this area is warranted. In the meantime, clinicians should carefully monitor their patients so that, if warranted, dose adjustments can be made quickly and safely to minimize negatively impacting the OUD therapy outcomes of patients.

Socially distant and out of reach: Unintended consequences of COVID-19 prevention efforts on transgender and gender non-binary populations in Puerto Rico.

Substance use disorders in the United States disproportionately affect minorities and socially vulnerable populations, particularly those at the intersection of racial and sexual minority status. Preceded by over a century-long subjugation to the U.S. government, a recent financial crisis, the devastating hurricanes of 2017, and a string of earthquakes at the end of 2019 and early 2020, the current COVID-19 pandemic is only the most recent disaster to disrupt the local health care system in Puerto Rico. However, the effects of the current emergency and imposed social distancing measures have only exacerbated the underlying vulnerabilities of the transgender and gender non-conforming (GNC) population made bare during these other recent disasters. Clinics and providers who treat patients with opioid use disorder (OUD) in Puerto Rico have had to develop their own safety protocols to limit the spread of the virus while trying to optimize current treatment protocols to maintain the stability of their patients. Despite these measures, we have observed a reduction in the ability of local organizations to outreach to already disconnected transgender and GNC individuals with OUD. For example, due to the government-imposed curfew that began March 15, 2020, some providers engaged in outreach with transgender and GNC sex workers have eliminated nighttime outreach completely. Additionally, a research project surveying all buprenorphine prescribers in Puerto Rico has found that few have received training in treating this vulnerable population, and even fewer report that they are currently providing treatment for transgender or GNC individuals. If Puerto Rico is to address this problem of gross under-representation of a population known to be disproportionately affected by substance use disorders, Puerto Rico must address structural factors to prevent this disparity from widening further during the inevitable future disasters our health care system will face.

Pharmacokinetic Characterization and External Evaluation of a Quantitative Framework of Sublingual Buprenorphine in Patients with an Opioid Disorder in Puerto Rico.

BACKGROUND: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. METHODS: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. RESULTS: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (tmax = 1.5 ± 0.7 h, Co = 1.6 ± 1.4 ng/mL, Cmax= 7.1 ± 6 ng/mL, and AUC0-8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC0-8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (ka = 2.54 h-1), distribution (k12= 2.34 h-1, k14 = 1.29 h-1), metabolism (k24 = 1.28 × 10-1 h-1, k23 = 6.43 × 10-2 h-1, k35 = 1.23 × 10-1 h-1, k45 = 8.73 × 10-1 h-1), and elimination (k30 = 3.81 × 10-3 h-1, k50 = 1.27 × 10-1 h-1) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. CONCLUSIONS: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico.