Obstetric pain management for pregnant women with opioid use disorder: A qualitative and quantitative comparison of patient and provider perspectives (QUEST study).

BACKGROUND AND AIM: Patients with opioid use disorder (OUD) may experience inadequate pain management especially during childbirth. This study assessed and compared patient and provider perspectives on analgesia during and after delivery in women with OUD. DESIGN: Prospective cohort, mixed method design including semi-structured interviews and structured surveys with pregnant or recently pregnant patients (n = 17) and provider (n = 15) groups. SETTING: Prenatal clinics and hospital postpartum units. PARTICIPANTS: Patients were pregnant women with OUD currently treated with methadone (n = 1) or buprenorphine (n = 16). Providers were obstetricians (n = 5), obstetric nurses (n = 5) and anesthesiologists (n = 5). MEASUREMENTS: Validated questionnaires were completed by both groups; patient interviews were conducted during the third trimester and at 5 days post-delivery. Patient topics included pain management preferences, analgesia satisfaction and attitudes toward pain. Provider topics included labor and postpartum pain management perspectives. Interviews were independently coded and qualitatively analyzed for major themes. FINDINGS: Five major themes emerged from patient interviews: (1) neuraxial blockade was endorsed for labor pain; (2) otherwise, limited pain control options were perceived; (3) no consensus around use of opioids for pain; (4) non-opioid options should be available; and (5) provider communication and health-care system issues act as barriers to adequate pain management. Provider perspective themes included the following: (1) unique challenges in pain management for patients with OUD; (2) confusion on how to plan for and make perinatal adjustments to medication for OUD; (3) discrepant views on use of opioids for pain management; (4) endorsement of non-pharmacological and non-opioid options; and (5) need for improved provider collaboration in developing pain management plans. CONCLUSIONS: Patients with opioid use disorder and health-care providers prioritize pain management during and after childbirth, but have discrepant views on use of opioids and other pain management options. Inadequate care coordination and discrepancies in opinions need to be addressed both within care teams and between patients and providers. Clinicians would benefit from better evidence to guide clinical care of patients with OUD for patient-centered pain management.

NSS-Bridge Device for Post-Cesarean Delivery Analgesia: A Randomized Controlled Trial.

Introduction: Percutaneous auricular nerve stimulation has been used for the treatment of symptoms associated with opioid withdrawal, including abdominal pain, nausea, and general discomfort. However, its potential utility for pain management and opioid minimization after surgery has not been investigated. The purpose of this study was to test the feasibility and acceptability of a trial protocol designed to assess the effectiveness of the NSS2-Bridge device as a non-pharmacologic alternative to opioids after cesarean delivery. Methods: In a randomized control design, healthy women receiving cesarean delivery were randomized to receive the active device, placebo device, or no device. Devices were placed on the ear following cesarean delivery and left in place for 5 days. Feasibility and acceptability of the device was assessed by patient reports of device tolerability (rated on a 100mm visual analog scale where 0 is not tolerable at all and 100 is the most tolerable) as well as qualitative reporting. Additional outcomes assessed included proportion of patients not using opioids in hospital, as well as pain at rest, pain with movement, and total opioid consumption in the hospital and for the first 5 days after surgery. Results: There were 60 patients included in the final analysis. Device tolerability was rated highly, with an average daily score of >75 mm on the visual analog scale. The trial retention rate was 89.7% with most exclusions (42.9%) occurring due to unanticipated development of care complexity (e.g., hemorrhage and additional surgical procedures), with only 1 exclusion (14.3%) due to device discomfort. The active device group achieved the highest proportion of opioid-free hospitalizations (40%) compared to placebo (20%) and no device groups (30%). Pain at rest and with movement was similar between treatment groups. Conclusions: This trial protocol designed to test the efficacy of NSS2-Bridge device for post-cesarean pain management is feasible and acceptable. Larger proportions of patients not using opioids in the active device group justifies additional investigation on device effectiveness in pregnant and postpartum people at highest risk for pain.

Associations between postpartum pain, mood, and maternal-infant attachment and parenting outcomes.

Pain and depression are interrelated, and worse postpartum pain has been associated with postpartum depression. It remains unclear whether improved pain and mood after delivery can also improve maternal parenting. Few studies have examined relationships between postpartum pain and negative mood (anxiety or depression) or their effects on parent-infant relationship outcomes. The purpose of this study was to explore the relationships between postpartum pain, mood, parent-infant attachment, parenting self-efficacy, and infant development. This was a prospective longitudinal observational pilot study of nulliparous women enrolled at the third trimester and presenting for labor and delivery at term gestation. Baseline third trimester assessments included validated inventories of pain (the brief pain inventory, BPI), depression (the Edinburgh postnatal depression screen, EPDS), anxiety (the state trait anxiety inventory, STAI), multidimensional scale of perceived social support (perceived social support scale, MSPSS) and perceived stress scale (PSS). Demographic and labor characteristics were recorded. At 6 weeks and 3 months postpartum, self-reported assessments included EPDS, STAI, BPI, maternal parent infant attachment scale (MPAS), and perceived maternal parenting self-efficacy (PMP-SE). Child development outcomes were assessed at 6 weeks and 3 months using the Ages and Stages Questionnaire (ASQ). Univariable linear regression assessed the relationships between pain and parenting outcomes (MPAS and PMP-SE), including potential interactions between pain and mood for parenting outcomes. Generalized linear modeling was used to explore the relationships between postpartum pain, parenting outcomes, and child development outcomes. Of 187 subjects, 87 had complete data on parent-infant attachment and parenting self-efficacy data at 3 months. Lower "pain right now" scores (BPI) on postpartum day 1 was associated with higher maternal-infant attachment (MPAS) at 6 weeks postpartum (Estimate - 1.8, 95% CI - 3.4 to - 0.2, P < 0.03) but not at 3 months (Estimate 0.23 95% CI - 1.1 to 1.6, P = 0.7). Higher depression (EPDS) scores at 6 weeks were also associated with lower MPAS scores at 6 weeks (Estimate - 1.24, 95% CI - 2.07 to - 0.40, P = 0.004). However, there was no evidence that the relationship between pain and MPAS varied by depression score at 6 weeks (P = 0.42). Pain scores at baseline, six weeks, or three months did not correlate with parenting outcomes (MPAS, PMP-SE) at six weeks or three months. Results of the generalized linear modeling revealed relationships between pain, age, anxiety (STAI), and depression (EPDS) predictors, and the outcomes of parenting (MPAS, PMP-SE) and gross motor and personal-social (ASQ) aspects of infant development. There is a pattern of association between worse postpartum pain, anxiety, and depression with worse parenting outcomes. Depression and pain may also affect infant development, but future work is required to replicate and characterize these potential relationships.

Assessment of Angiogenesis and Cell Survivability of an Inkjet Bioprinted Biological Implant in an Animal Model.

The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues.

Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19-A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium.

Importance: The COVID-19 pandemic continues to affect millions of people globally, with increasing reports of neurological manifestations but limited data on their incidence and associations with outcome. Objective: To determine the neurological phenotypes, incidence, and outcomes among adults hospitalized with COVID-19. Design, Setting, and Participants: This cohort study included patients with clinically diagnosed or laboratory-confirmed COVID-19 at 28 centers, representing 13 countries and 4 continents. The study was performed by the Global Consortium Study of Neurologic Dysfunction in COVID-19 (GCS-NeuroCOVID) from March 1 to September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENERGY) from March to October 2020. Three cohorts were included: (1) the GCS-NeuroCOVID all COVID-19 cohort (n = 3055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; (2) the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and (3) the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation. Exposures: Clinically diagnosed or laboratory-confirmed COVID-19. Main Outcomes and Measures: Neurological phenotypes were classified as self-reported symptoms or neurological signs and/or syndromes assessed by clinical evaluation. Composite incidence was reported for groups with at least 1 neurological manifestation. The main outcome measure was in-hospital mortality. Results: Of the 3055 patients in the all COVID-19 cohort, 1742 (57%) were men, and the mean age was 59.9 years (95% CI, 59.3-60.6 years). Of the 475 patients in the COVID-19 neurological cohort, 262 (55%) were men, and the mean age was 62.6 years (95% CI, 61.1-64.1 years). Of the 214 patients in the ENERGY cohort, 133 (62%) were men, and the mean age was 67 years (95% CI, 52-78 years). A total of 3083 of 3743 patients (82%) across cohorts had any neurological manifestation (self-reported neurological symptoms and/or clinically captured neurological sign and/or syndrome). The most common self-reported symptoms included headache (1385 of 3732 patients [37%]) and anosmia or ageusia (977 of 3700 patients [26%]). The most prevalent neurological signs and/or syndromes were acute encephalopathy (1845 of 3740 patients [49%]), coma (649 of 3737 patients [17%]), and stroke (222 of 3737 patients [6%]), while meningitis and/or encephalitis were rare (19 of 3741 patients [0.5%]). Presence of clinically captured neurologic signs and/or syndromes was associated with increased risk of in-hospital death (adjusted odds ratio [aOR], 5.99; 95% CI, 4.33-8.28) after adjusting for study site, age, sex, race, and ethnicity. Presence of preexisting neurological disorders (aOR, 2.23; 95% CI, 1.80-2.75) was associated with increased risk of developing neurological signs and/or syndromes with COVID-19. Conclusions and Relevance: In this multicohort study, neurological manifestations were prevalent among patients hospitalized with COVID-19 and were associated with higher in-hospital mortality. Preexisting neurological disorders were associated with increased risk of developing neurological signs and/or syndromes in COVID-19.

The Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Development of Case Report Forms for Global Use.

Since its original report in January 2020, the coronavirus disease 2019 (COVID-19) due to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly become one of the deadliest global pandemics. Early reports indicate possible neurological manifestations associated with COVID-19, with symptoms ranging from mild to severe, highly variable prevalence rates, and uncertainty regarding causal or coincidental occurrence of symptoms. As neurological involvement of any systemic disease is frequently associated with adverse effects on morbidity and mortality, obtaining accurate and consistent global data on the extent to which COVID-19 may impact the nervous system is urgently needed. To address this need, investigators from the Neurocritical Care Society launched the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID). The GCS-NeuroCOVID consortium rapidly implemented a Tier 1, pragmatic study to establish phenotypes and prevalence of neurological manifestations of COVID-19. A key component of this global collaboration is development and application of common data elements (CDEs) and definitions to facilitate rigorous and systematic data collection across resource settings. Integration of these elements is critical to reduce heterogeneity of data and allow for future high-quality meta-analyses. The GCS-NeuroCOVID consortium specifically designed these elements to be feasible for clinician investigators during a global pandemic when healthcare systems are likely overwhelmed and resources for research may be limited. Elements include pediatric components and translated versions to facilitate collaboration and data capture in Latin America, one of the epicenters of this global outbreak. In this manuscript, we share the specific data elements, definitions, and rationale for the adult and pediatric CDEs for Tier 1 of the GCS-NeuroCOVID consortium, as well as the translated versions adapted for use in Latin America. Global efforts are underway to further harmonize CDEs with other large consortia studying neurological and general aspects of COVID-19 infections. Ultimately, the GCS-NeuroCOVID consortium network provides a critical infrastructure to systematically capture data in current and future unanticipated disasters and disease outbreaks.