Examining the Stability and Predictive Utility of Across- and Within-Domain Intra-Individual Variability in Mild Cognitive Impairment.

OBJECTIVE: Dispersion is a form of intra-individual variability across neuropsychological tests that has been shown to predict cognitive decline. However, few studies have investigated the stability and predictive utility of both across- and within-domain dispersion. The current study aims to fill these gaps in the literature by examining multiple indices of dispersion in a longitudinal clinical sample of individuals diagnosed with mild cognitive impairment (MCI) at baseline. METHOD: Two hundred thirty-eight MCI patients from a cognitive disorders clinic underwent testing at baseline and after approximately 1.5 years. Linear regression was used to examine whether baseline across- and within-domain dispersion predicted cognitive decline in individuals whose diagnostic classification progressed to dementia (i.e., MCI-Decline) and those who retained an MCI diagnosis at follow-up (i.e., MCI-Stable). Cognitive decline was operationalized dichotomously using group status and continuously using standardized regression-based (SRB) z-scores. RESULTS: Dispersion variables at baseline and follow-up were positively correlated in both groups, with the exception of within-domain executive functioning and language dispersion in the MCI-Decline group. None of the dispersion variables predicted diagnostic conversion to MCI. Using SRB z-scores, greater across-domain dispersion predicted greater overall cognitive decline at follow-up, but this was not the case for within-domain variables with the exception of visuospatial skills. CONCLUSIONS: Results suggest that across- and within-domain dispersion are relatively stable across time, and that across-domain dispersion is predictive of subtle cognitive decline in patients with MCI. However, these results also highlight that findings may differ based on the tests included in dispersion calculations.

A Potential Measure of Premorbid Functioning: Evaluating the Construct Validity of the Author and Magazine Recognition Tests.

OBJECTIVE: To establish convergent and discriminant validity for a combined measure of print exposure (i.e., Author Recognition Test and Magazine Recognition Test [ART/MRT]) and assess its potential utility for estimating premorbid cognitive functioning. METHOD: Community-dwelling older adults (N = 84; 95% non-Hispanic White) completed the ART/MRT, Test of Premorbid Functioning (ToPF), Dementia Rating Scale - 2nd Edition (DRS-2), Hopkins Verbal Learning Test - Revised (HVLT-R-DR), and select subtests from the Delis-Kaplan Executive Functioning System (D-KEFS) as measures of executive functioning (i.e., D-KEFS-EF) and processing speed (i.e., D-KEFS-PS). Pearson correlations and linear regressions were used to examine the relationships between the ART/MRT, cognition, and demographics. RESULTS: Cognitive scores, with the exception of HVLT-R-DR, were positively correlated with ART/MRT score such that better cognitive performance was associated with greater print exposure (range r = 0.39-0.49). ART/MRT score was positively correlated with years of education and negatively correlated with age. ToPF and DRS-2 differentially and uniquely predicted ART/MRT score beyond the other cognitive and demographic variables and beyond each other. CONCLUSIONS: Findings indicate that measures of print exposure reflect crystallized knowledge but may also capture fluid abilities that may be more vulnerable to age-related decline or neurodegeneration. Assessment of print exposure may offer an alternative to word reading measures that may be inappropriate for translation into other languages and for use with individuals with certain language difficulties.

Validation of RNA Extraction Methods and Suitable Reference Genes for Gene Expression Studies in Developing Fetal Human Inner Ear Tissue.

A comprehensive gene expression investigation requires high-quality RNA extraction, in sufficient amounts for real-time quantitative polymerase chain reaction and next-generation sequencing. In this work, we compared different RNA extraction methods and evaluated different reference genes for gene expression studies in the fetal human inner ear. We compared the RNA extracted from formalin-fixed paraffin-embedded tissue with fresh tissue stored at -80 °C in RNAlater solution and validated the expression stability of 12 reference genes (from gestational week 11 to 19). The RNA from fresh tissue in RNAlater resulted in higher amounts and a better quality of RNA than that from the paraffin-embedded tissue. The reference gene evaluation exhibited four stably expressed reference genes (B2M, HPRT1, GAPDH and GUSB). The selected reference genes were then used to examine the effect on the expression outcome of target genes (OTOF and TECTA), which are known to be regulated during inner ear development. The selected reference genes displayed no differences in the expression profile of OTOF and TECTA, which was confirmed by immunostaining. The results underline the importance of the choice of the RNA extraction method and reference genes used in gene expression studies.

Synchronous versus metachronous spinal metastasis: a comparative study of survival outcomes following neurosurgical treatment.

PURPOSE: Patients with spinal metastases (SM) from solid neoplasms typically exhibit progression to an advanced cancer stage. Such metastases can either develop concurrently with an existing cancer diagnosis (termed metachronous SM) or emerge as the initial indication of an undiagnosed malignancy (referred to as synchronous SM). The present study investigates the prognostic implications of synchronous compared to metachronous SM following surgical resection. METHODS: From 2015 to 2020, a total of 211 individuals underwent surgical intervention for SM at our neuro-oncology facility. We conducted a survival analysis starting from the date of the neurosurgical procedure, comparing those diagnosed with synchronous SM against those with metachronous SM. RESULTS: The predominant primary tumor types included lung cancer (23%), prostate cancer (21%), and breast cancer (11.3%). Of the participants, 97 (46%) had synchronous SM, while 114 (54%) had metachronous SM. The median overall survival post-surgery for those with synchronous SM was 13.5 months (95% confidence interval (CI) 6.1-15.8) compared to 13 months (95% CI 7.7-14.2) for those with metachronous SM (p = 0.74). CONCLUSIONS: Our findings suggest that the timing of SM diagnosis (synchronous versus metachronous) does not significantly affect survival outcomes following neurosurgical treatment for SM. These results support the consideration of neurosurgical procedures regardless of the temporal pattern of SM manifestation.

Associations between the resting EEG aperiodic slope and broad domains of cognitive ability.

Recent studies suggest that the EEG aperiodic exponent (often represented as a slope in log-log space) is sensitive to individual differences in momentary cognitive skills such as selective attention and information processing speed. However, findings are mixed, and most of the studies have focused on just a narrow range of cognitive domains. This study used an archival dataset to help clarify associations between resting aperiodic features and broad domains of cognitive ability, which vary in their demands on momentary processing. Undergraduates (N = 166) of age 18-52 years completed a resting EEG session as well as a standardized, individually administered assessment of cognitive ability that included measures of processing speed, working memory, and higher-order visuospatial and verbal skills. A subsample (n = 110) also completed a computerized reaction time task with three difficulty levels. Data reduction analyses revealed strong correlations between the aperiodic offset and slope across electrodes, and a single component accounted for ~60% of variance in slopes across the scalp, in both eyes-closed and eyes-open conditions. Structural equation models did not support relations between the slope and specific domains tapping momentary processes. However, secondary analyses indicated that the eyes-open slope was related to higher overall performance, as represented by a single general ability factor. A latent reaction time variable was significantly inversely related to both eyes-closed and eyes-open resting exponents, such that faster reaction times were associated with steeper slopes. These findings support and help clarify the relation of the resting EEG exponent to individual differences in cognitive skills.

Kratom Use Among Pregnant and Lactating Individuals With Substance Use Disorder.

OBJECTIVE: Kratom ( Mitragyna speciosa ) use in pregnancy is associated with maternal and neonatal opioid withdrawal syndrome. However, kratom use patterns in the population of peripartum and postpartum individuals with substance use disorder (SUD) are unknown. The aim of this study was to determine the proportion of pregnant and postpartum individuals with SUD who report using kratom in pregnancy or lactation and the reasons for their use. METHODS: We conducted an anonymous survey of pregnant and postpartum individuals receiving care at a single center's multidisciplinary prenatal clinic for individuals with SUD. We collected participants' demographic and pregnancy characteristics. We assessed ever use of kratom, kratom use during pregnancy or lactation, and reasons for kratom use. Descriptive statistics were used to summarize the data. RESULTS: From January 2021 to May 2021, a total of 80 surveys were collected (81% response rate of 98 eligible individuals). Most respondents were pregnant (n = 50 [62.5%]). The most frequent substance(s) of use were opioids (n = 50 [62.5%]) and methamphetamine (n = 39 [48.8%]). Many (n = 26 [32.5%]) reported ever use of kratom use. Of all respondents, 4 (5%) reported use during pregnancy, and 1 (1%) reported use during lactation. Kratom was primarily used to relieve opioid withdrawal symptoms and for relaxation, pain control, and stress relief. CONCLUSION: In a survey of pregnant and postpartum individuals with SUD at a single high-risk pregnancy clinic, ever use of kratom was frequent, whereas peripartum use was rare.

EMG measured reaction time as a predictor of invalid symptom report in psychosomatic patients.

Background: Symptom validity tests (SVTs) and performance validity tests (PVTs) are important tools in sociomedical assessments, especially in the psychosomatic context where diagnoses mainly depend on clinical observation and self-report measures. This study examined the relationship between reaction times (RTs) and scores on the Structured Inventory of Malingered Symptomatology (SIMS). It was proposed that slower RTs and larger standard deviations of reaction times (RTSDs) would be observed in participants who scored above the SIMS cut-off (>16). Methods: Direct surface electromyography (EMG) was used to capture RTs during a computer-based RT test in 152 inpatients from a psychosomatic rehabilitation clinic in Germany. Correlation analyses and Mann-Whitney U were used to examine the relationship between RTs and SIMS scores and to assess the potential impact of covariates such as demographics, medical history, and vocational challenges on RTs. Therefore, dichotomized groups based on each potential covariate were compared. Results: Significantly longer RTs and larger RTSDs were found in participants who scored above the SIMS cut-off. Current treatment with psychopharmacological medication, diagnosis of depression, and age had no significant influence on the RT measures. However, work-related problems had a significant impact on RTSDs. Conclusion: There was a significant relationship between longer and more inconsistent RTs and indicators of exaggerated or feigned symptom report on the SIMS in psychosomatic rehabilitation inpatients. Findings from this study provide a basis for future research developing a new RT-based PVT.

Postpartum Extended-Release Buprenorphine Tissue Necrosis.

BACKGROUND: Extended-release buprenorphine (XRB) may improve medication for opioid use disorder continuation among postpartum individuals. However, obstetric clinicians have relatively little experience with XRB. We describe two cases of XRB-related tissue necrosis in postpartum individuals to highlight recommended injection technique and management strategies for this rare complication. CASES: One patient developed tissue necrosis after her initial injection. Her wound was expectantly managed. Another patient on long-term XRB developed tissue necrosis within 1 day of injection. General surgery excised the depot. Both instances were attributed to injection of XRB intradermally rather than subcutaneously. Both patients continued monthly XRB without recurrence, suggesting that this complication is not an allergy. CONCLUSION: Clinicians should be able to prevent, recognize, and manage tissue necrosis, a rare complication of XRB injection.

Spatial transcriptomics reveals novel genes during the remodelling of the embryonic human arterial valves.

Abnormalities of the arterial valves, including bicuspid aortic valve (BAV) are amongst the most common congenital defects and are a significant cause of morbidity as well as predisposition to disease in later life. Despite this, and compounded by their small size and relative inaccessibility, there is still much to understand about how the arterial valves form and remodel during embryogenesis, both at the morphological and genetic level. Here we set out to address this in human embryos, using Spatial Transcriptomics (ST). We show that ST can be used to investigate the transcriptome of the developing arterial valves, circumventing the problems of accurately dissecting out these tiny structures from the developing embryo. We show that the transcriptome of CS16 and CS19 arterial valves overlap considerably, despite being several days apart in terms of human gestation, and that expression data confirm that the great majority of the most differentially expressed genes are valve-specific. Moreover, we show that the transcriptome of the human arterial valves overlaps with that of mouse atrioventricular valves from a range of gestations, validating our dataset but also highlighting novel genes, including four that are not found in the mouse genome and have not previously been linked to valve development. Importantly, our data suggests that valve transcriptomes are under-represented when using commonly used databases to filter for genes important in cardiac development; this means that causative variants in valve-related genes may be excluded during filtering for genomic data analyses for, for example, BAV. Finally, we highlight "novel" pathways that likely play important roles in arterial valve development, showing that mouse knockouts of RBP1 have arterial valve defects. Thus, this study has confirmed the utility of ST for studies of the developing heart valves and broadens our knowledge of the genes and signalling pathways important in human valve development.

Assessing Longitudinal Cognitive Change in Mild Cognitive Impairment Using Estimated Standardized Regression-Based Formulas.

BACKGROUND: Cognitive change in mild cognitive impairment (MCI), a likely prodrome to Alzheimer's disease, can be tracked with repeated neuropsychological assessments, but there has been little work quantifying these changes over time. Cognitive change can be statistically examined using standardized regression-based (SRB) formulas, which yield a z-score indicating amount of change compared to a normative group. OBJECTIVE: To use SRB z-scores to quantify cognitive change in a sample of patients classified as MCI at baseline, and to compare cognitive change in those who remained MCI on follow-up (MCI-Stable) and those who progressed to dementia (MCI-Decline). METHODS: Using 283 MCI patients from a cognitive disorders clinic who were re-assessed after approximately one- and one-half years, SRB z-scores were calculated for each test in a comprehensive neuropsychological battery for each participant. RESULTS: There was a significant decline between timepoints across all cognitive tests, with the greatest amount of decline on tests of learning and memory. Group differences were seen on nearly all cognitive tests, with the MCI-Decline group showing more decline (i.e., significantly larger and negative z-scores) than the MCI-Stable participants. Notable cognitive decline was also observed in the MCI-Stable group, with z-scores ranging from -0.01 - -2.24 compared to normative data. CONCLUSION: This study highlights the amount of cognitive decline that occurs in MCI, including for those who remain "stable" and those who progress to dementia. It also demonstrates the value of the SRB method in more clearly quantifying cognitive decline, which may help identify individuals most vulnerable to MCI progression.

Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates.

BACKGROUND: The aim of this study was to investigate the association between inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6)) and sepsis severity (neonatal-Sequential-Organ-Failure-Assessment (nSOFA)) and neurodevelopmental outcomes at 2 years, among very preterm neonates. METHODS: Data on preterm neonates (gestational age <30 weeks) from 2016 until 2020 were reviewed. Outcomes of interest were NDI (no, mild, severe) and the motor and cognitive score on the Dutch-Bayley-Scales-of-Infant-and-Toddler-Development (Bayley-III-NL) assessed at the corrected age of 2 years. Logistic and linear regression analysis were used for categorical and continuous outcomes, respectively. All analyses were adjusted for gestational age, sex and birthweight-for-gestational-age SD-score. RESULTS: In total 410 patients were eligible for analysis. Maximum CRP concentrations were associated with lower motor and cognitive scores (effect estimate -0.03 points,(95% CI -0.07; -0.00) and -0.03 points,(95% CI -0.06; -0.004), respectively) and increased risk of severe NDI (odds ratio (OR) 1.01, (95% CI 1.00; 1.01)). High nSOFA scores (≥4) during sepsis episodes were associated with an increased risk of mild NDI (OR 2.01, (95% CI 1.34; 3.03)). There were no consistent associations between IL-6, PCT and the outcomes of interest. CONCLUSION: High CRP concentrations and sepsis severity in preterm neonates seem to be associated with neurodevelopmental outcomes in survivors at the age of 2 years. IMPACT STATEMENT: The level of inflammation and sepsis severity are associated with neurodevelopmental outcome in preterm neonates at 2 years of corrected age. Sepsis is a major health issue in preterm neonates and can lead to brain damage and impaired neurodevelopment. Biomarkers can be determined to assess the level of inflammation. However, the relation of inflammatory biomarkers with neurodevelopmental outcome is not known. The level of inflammation and sepsis severity are related to neurodevelopmental outcome in preterm neonates. Maximum CRP concentration and high nSOFA scores are associated with an increased risk of neurodevelopmental impairment in survivors at the corrected age of 2 years.

Postoperative prolonged mechanical ventilation in patients with surgically treated pyogenic spondylodiscitis: a surrogate endpoint for early postoperative mortality.

Surgical procedures with spinal instrumentation constitute a prevalent and occasionally highly indicated treatment modality in patients with pyogenic spondylodiscitis (PSD). However, surgical therapy might be associated with the need of prolonged postoperative intensive care medicine which in turn might impair intended operative benefit. Therefore, we analyzed prolonged mechanical ventilation (PMV) as an indicator variable for such intensive care treatment with regard to potential correlations with mortality in this vulnerable patient cohort. Between 2012 and 2018, 177 consecutive patients received stabilization surgery for PSD at the authors' neurosurgical department. PMV was defined as postoperative mechanical ventilation of more than 24 h. A multivariable analysis was performed to identify independent predictors for 30-day mortality. Twenty-three out of 177 patients (13%) with PSD suffered from postoperative PMV. Thirty-day mortality rate was 5%. Multivariable analysis identified "spinal empyema" (p = 0.02, odds ratio (OR) 6.2, 95% confidence interval (CI) 1.3-30.2), "Charlson comorbidity index (CCI) > 2" (p = 0.04, OR 4.0, 95% CI 1.0-15.5), "early postoperative complications (PSIs)" (p = 0.001, OR 17.1, 95% CI 3.1-96.0) and "PMV > 24 hrs" (p = 0.002, OR 13.0, 95% CI 2.7-63.8) as significant and independent predictors for early postoperative mortality. The present study indicates PMV to significantly correlate to elevated early postoperative mortality rates following stabilization surgery for PSD. These results might entail further scientific efforts to investigate PMV as a so far underestimated negative prognostic factor in the surgical treatment of PSD.

Next generation organoid engineering to replace animals in cancer drug testing.

Cancer therapies have several clinical challenges associated with them, namely treatment toxicity, treatment resistance and relapse. Due to factors ranging from patient profiles to the tumour microenvironment (TME), there are several hurdles to overcome in developing effective treatments that have low toxicity that can mitigate emergence of resistance and occurrence of relapse. De novo cancer development has the highest drug attrition rates with only 1 in 10,000 preclinical candidates reaching the market. To alleviate this high attrition rate, more mimetic and sustainable preclinical models that can capture the disease biology as in the patient, are required. Organoids and next generation 3D tissue engineering is an emerging area that aims to address this problem. Advancement of three-dimensional (3D) in vitro cultures into complex organoid models incorporating multiple cell types alongside acellular aspects of tissue microenvironments can provide a system for therapeutic testing. Development of microfluidic technologies have furthermore increased the biomimetic nature of these models. Additionally, 3D bio-printing facilitates generation of tractable ex vivo models in a controlled, scalable and reproducible manner. In this review we highlight some of the traditional preclinical models used in cancer drug testing and debate how next generation organoids are being used to replace not only animal models, but also some of the more elementary in vitro approaches, such as cell lines. Examples of applications of the various models will be appraised alongside the future challenges that still need to be overcome.

Nonfatal Overdoses Among Pregnant Individuals With Opioid Use Disorder.

Little is understood about overdose history among pregnant individuals with opioid use disorder (OUD). We performed a cross-sectional secondary analysis of data from the OPTI-Mom 2.0 (Optimizing Pregnancy and Treatment Interventions for Moms 2.0) study (NCT03833245), a multi-site randomized controlled trial of patient navigation and usual care. We summarized participant demographics, overdose history, and substances involved in most recent overdose. Of the 102 participants with severe OUD included, 64.7% (95% CI 54.8-73.4%) had a reported a history of an overdose event and 41.2% (95% CI 31-52%) reported at least one overdose within the past year. In the most recent overdose, 81.8% (95% CI 70.4-89.5%) reported using opioids and 30.3% (95% CI 20.3-42.6%) reported using sedatives. These findings suggest need for heightened awareness of overdose-reduction and harm-reduction strategies in this population.

What to Expect With Pregnant or Postpartum Prescribing of Extended-Release Buprenorphine (CAM2038).

Weekly and monthly CAM2038 (Brixadi®) extended-release subcutaneous buprenorphine (XR bup) has been available in Europe and Australia for several years and was approved by the Food and Drug Administration in May 2023. Little is known about the clinical experience of patients and providers using this new medication during prenatal care. Two cases of pregnant persons with opioid use disorder receiving weekly XR bup in an ongoing randomized multi-site outpatient clinical trial are presented along with a brief review of the pharmacology and literature on XR bup formulations. The cases in pregnancy illustrate how treatment with the weekly formulation is initiated including how to make dose adjustments, which may be necessary given the longer half-life; it takes 1 month to achieve steady state. Injection site pain with medication administration was time limited and managed readily. Other injection site reactions experienced included subcutaneous erythema and induration that was delayed in onset and typically mild, resolving with minimal intervention. Delivery management and breastfeeding recommendations while on weekly XR bup were not different compared to sublingual buprenorphine (SL bup). Weekly XR bup is a new treatment for opioid use disorder that may be used in the obstetric population. Obstetric and addiction medicine clinicians should be aware of this new formulation as its use is expected to increase.

Whole Genome Sequencing Analysis of Effects of CRISPR/Cas9 in Komagataella phaffii: A Budding Yeast in Distress.

The industrially important non-conventional yeast Komagataella phaffii suffers from low rates of homologous recombination, making site specific genetic engineering tedious. Therefore, genome editing using CRISPR/Cas represents a simple and efficient alternative. To characterize on- and off-target mutations caused by CRISPR/Cas9 followed by non-homologous end joining repair, we chose a diverse set of CRISPR/Cas targets and conducted whole genome sequencing on 146 CRISPR/Cas9 engineered single colonies. We compared the outcomes of single target CRISPR transformations to double target experiments. Furthermore, we examined the extent of possible large deletions by targeting a large genomic region, which is likely to be non-essential. The analysis of on-target mutations showed an unexpectedly high number of large deletions and chromosomal rearrangements at the CRISPR target loci. We also observed an increase of on-target structural variants in double target experiments as compared to single target experiments. Targeting of two loci within a putatively non-essential region led to a truncation of chromosome 3 at the target locus in multiple cases, causing the deletion of 20 genes and several ribosomal DNA repeats. The identified de novo off-target mutations were rare and randomly distributed, with no apparent connection to unspecific CRISPR/Cas9 off-target binding sites.

Safety Evaluation of Cervical Dorsal Instrumentation in Geriatric Patients: Experience at a Level 1 Center for Spinal Surgery-A Single Center Cohort Study.

Objective: Dorsal instrumentation of the cervical spine is an established treatment in spine surgery. However, careful planning is required, particularly in elderly patients. This study evaluates early clinical outcomes in geriatric patients undergoing complex spine surgery. Methods: In this retrospective, single center cohort study, we included all geriatric patients (aged ≥65 years) who underwent dorsal instrumentation between January 2013 and December 2020. We analyzed postoperative complications and the 30-day in-hospital mortality rate. Furthermore, the Charlson comorbidity index (CCI) and Clavien-Dindo grading system (CDG) were used to assess the patients' comorbidity burden. Results: In total, 153 patients were identified and included. The mean age of patients was 78 years (SD ± 7). Traumatic injury (53.6%) was the most common reason for surgery. 60.8% of the patients underwent dorsal instrumentation with 3 or more levels. The most common comorbidities were arterial hypertension (64%), diabetes mellitus (22.2%), coronary heart disease and atrial fibrillation (19.6%). The most common adverse event (AE) was pneumonia (4%) and the most common surgery-related complication was wound infection (5.2%). Among patients categorized as high risk for AE (CCI > 5), 14.6% suffered a postoperative AE. In our univariate analysis, we found no risk factors for high rates of complications or mortality. Conclusion: Our data demonstrates that older patients were at no significant risk of postoperative complications. The CCI/CDG scores may identify patients at higher risk for adverse events after dorsal instrumentation, and these assessments should become an essential component of stratification in this older patient population.

Mitochondrial metabolism in macrophages.

Mitochondria are considered to be the powerhouse of the cell. Normal functioning of the mitochondria is not only essential for cellular energy production but also for several immunomodulatory processes. Macrophages operate in metabolic niches and rely on rapid adaptation to specific metabolic conditions such as hypoxia, nutrient limitations, or reactive oxygen species to neutralize pathogens. In this regard, the fast reprogramming of mitochondrial metabolism is indispensable to provide the cells with the necessary energy and intermediates to efficiently mount the inflammatory response. Moreover, mitochondria act as a physical scaffold for several proteins involved in immune signaling cascades and their dysfunction is immediately associated with a dampened immune response. In this review, we put special focus on mitochondrial function in macrophages and highlight how mitochondrial metabolism is involved in macrophage activation.

Buprenorphine X-waiver exemption - beyond the basics for the obstetrical provider.

Buprenorphine is 1 of 3 medications approved by the US Food and Drug Administration for the treatment of opioid use disorder, and practitioners must obtain a federal waiver to prescribe buprenorphine. Until recently, physicians and advanced practice clinicians were required to complete 8 and 24 hours of training, respectively, before applying for this waiver and to provide psychosocial services when prescribing buprenorphine to ≤30 patients. The US Department of Health and Human Services announced in April 2021 that eligible providers would be exempt from the educational requirement for certification, making the waiver more accessible for those intending to prescribe to ≤30 patients. Here, we reviewed the historic background to the exemption and provided practical guidelines to practitioners caring for obstetrical patients with opioid use disorder who are considering applying for the waiver for the first time. Because the educational requirements will no longer be required for X-waiver application, we reviewed fundamental topics and challenging scenarios that are often reviewed in certification courses.