Physical impairment during and between migraine attacks: A daily diary study of patients with chronic migraine.

OBJECTIVE: While a substantial body of research describes the disabling impacts of migraine attacks, less research has described the impacts of migraine on physical functioning between migraine attacks. The objective of this study is to describe physical impairment during and between migraine attacks as a dimension of burden experienced by people living with chronic migraine. METHODS: The physical impairment domain of the Migraine Physical Function Impact Diary was recorded in headache diaries from the Medication Overuse Treatment Strategy trial. Days with moderate to severe headache were used to approximate migraine attacks. Factor analysis and regression analysis were used to describe associations between migraine and physical impairment. RESULTS: 77,662 headache diary entries from 720 participants were analyzed, including 25,414 days with moderate to severe headache, 19,149 days with mild headache, and 33,099 days with no headache. Mean physical impairment score was 41.5 (SD = 26.1) on days with moderate to severe headache, 12.8 (SD = 15.0) on days with mild headache, and 5.2 (SD = 13.1) on days with no headache. Physical impairment on days with mild headache and days with no headache was significantly associated with days since last moderate to severe headache, physical impairment with last moderate to severe headache, mild headache (compared to no headache), depression, hypersensitivities and cranial autonomic symptoms. CONCLUSIONS: Physical impairment occurs on migraine and non-migraine days. Study participants with frequent headaches, symptoms of depression, hypersensitivities and cranial autonomic symptoms experience physical impairment at a higher rate on days with no headache and days with mild headache.Clinical Trial Registration: ClinicalTrials.gov (NCT02764320).

Bayesian design of clinical trials using the scale transformed power prior.

There are many Bayesian design methods allowing for the incorporation of historical data for sample size determination (SSD) in situations where the outcome in the historical data is the same as the outcome of a new study. However, there is a dearth of methods supporting the incorporation of data from a previously completed clinical trial that investigated the same or similar treatment as the new trial but had a primary outcome that is different. We propose a simulation-based Bayesian SSD framework using the partial-borrowing scale transformed power prior (straPP). The partial-borrowing straPP is developed by applying a novel scale transformation to a traditional power prior on the parameters from the historical data model to make the information better align with the new data model. The scale transformation is based on the assumption that the standardized parameters (i.e., parameters multiplied by the square roots of their respective Fisher information matrices) are equal. To illustrate the method, we present results from simulation studies that use real data from a previously completed clinical trial to design a new clinical trial with a primary time-to-event endpoint.

Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies.

Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and NK cells have shown remarkable clinical efficacy in treating hematological malignancies, however current methods mainly utilize viral vectors which are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo via DNA transposon engineering is a more timely and cost-effective approach, yet has been held back by less efficient integration rates. Here, we report the development of a novel hyperactive TcBuster (TcB-M) transposase engineered through structure guided and in vitro evolution approaches that achieves high-efficiency integration of large, multicistronic CAR-expression cassettes in primary human cells. Our proof of principle TcB-M engineering of CAR-NK and CAR-T cells show low integrated vector copy number, a safe insertion site profile, robust in vitro function, and improves survival in a Burkitt lymphoma xenograft model in vivo. Overall, TcB-M is a versatile, safe, efficient and open-source option for the rapid manufacture and preclinical testing of primary human immune cell therapies through delivery of multicistronic large cargo via transposition.

Cell-type-resolved mosaicism reveals clonal dynamics of the human forebrain.

Debate remains around the anatomical origins of specific brain cell subtypes and lineage relationships within the human forebrain1-7. Thus, direct observation in the mature human brain is critical for a complete understanding of its structural organization and cellular origins. Here we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific mosaic variant barcode analysis. From four hemispheres and two different human neurotypical donors, we identified 287 and 780 mosaic variants, respectively, that were used to deconvolve clonal dynamics. Clonal spread and allele fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted than resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome transcriptome analysis at both a cell-type-specific and a single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of mosaic variants across 17 locations within one parietal lobe reveals that restriction of clonal spread in the anterior-posterior axis precedes restriction in the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus, cell-type-resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.

Psychobiography in sociocultural context: the application of culture-based theories of psychology on a culturally diverse historic subject pool.

In recent years the historical subject base in psychobiography has expanded from a traditional focus on White (Caucasian) subjects to a broader more culturally inclusive population of significant personalities throughout history. A critical component of strong multicultural psychobiography is the inclusion of anchoring theories of psychology that are rooted in socio-cultural-political context. To psychologically profile culturally diverse individuals with only traditional Western theories of psychology and psychiatry (e.g. medical models, psychodynamic, existential, cognitive-behavioral) limits the ability of the research to accurately capture the erlebnis (lived experience) of extraordinary individuals in proper cultural context. This article reviews specific psychological theories that have recently set a foundation for more nuanced and culturally contextualised psychological profiles of historic personalities who represent diverse racial/ethnic/cultural backgrounds. Among the theories covered are the Integrated African Psychology Perspective (IAPP), an Indigenous (Native American) model of psychobiography, as well as theories and models on Psychological Nigrescence (Black racial identity development), Intersectionality, Politicised Collective Identity (PCI), Queered Black Racial Identity Development (QBRID), and Adultification of Black Children, among others. Examples of applications of these culture-centered theories to psychobiography, drawn from the present authors recently completed psychobiographies, as well as from other researchers internationally, are presented.

Promoting psychobiography: models and perspectives from multiple countries.

This article promotes and advocates for the integration of psychobiography into academic training in psychology. While psychobiography has been foundational to the discipline of psychology since Freud's study of Leonardo da Vinci, its procedures and methods have been sorely neglected in academic psychology. Following a brief introduction to psychobiography, the authors provide a historical review of the specialty area, review the current scope of psychobiographical training in psychology, and summarize the benefits of psychobiography to both the training of students and the broader psychology field. Next, models and examples of psychobiography integration across three continents and five countries are provided. The article concludes with specific recommendations for advancing psychobiography in academic psychology.

Prescribing Benzodiazepines and Opioids and Clinical Characteristics Associated With 30-Day Hospital Return in Patients Aged ≥75 Years: Secondary Data Analysis.

PURPOSE: The current study compared prevalence of opioid or benzodiazepine (BZD) prescription and co-prescription of opioids and BZD at discharge and return to a community hospital within 30 days, as well as identified clinical characteristics associated with hospital return in patients aged ≥75 years. METHOD: A secondary analysis of a database created during implementation of the Safe Transitions for At Risk Patients program at a 400-bed community teaching hospital in south Florida was conducted. Multivariable logistic regression analyses were performed to identify significant demographic and clinical characteristics associated with return to the hospital within 30 days of discharge. RESULTS: A total of 24,262 participants (52.6% women) with a mean age of 85.3 (SD = 6.42) years were included. More than 20% in each central nervous system prescription group (i.e., opioids only, BZD only, opioids and BZD) returned to the hospital within 30 days of discharge. Demographic and chronic conditions (e.g., congestive heart failure, chronic obstructive pulmonary disease, diabetes) and poly-pharmacy were significant factors of a 30-day return to the hospital. CONCLUSION: Findings highlight the importance of hospital nurses' role in identifying high-risk patients, educating patients and caregivers, monitoring them closely, communicating with primary care physicians and specialists, and conducting intensive follow up via telephone to avoid 30-day rehospitalization. [Journal of Gerontological Nursing, 50(4), 25-33.].

Vaso-Lock for sutureless anastomosis in a pig arteriovenous loop model.

A vascular anastomosis is a critical surgical skill that involves connecting blood vessels. Traditional handsewn techniques can be challenging and resource intensive. To address these issues, we have developed a unique sutureless anastomotic device called Vaso-Lock. This intraluminal device connects free vascular ends using anchors to maintain traction and enable a rapid anastomosis. We tested the anastomotic capability of Vaso-Locks in a pig common carotid-internal jugular arteriovenous model. The use of Vaso-Lock allowed us to accomplish this procedure in less than 10 min, in contrast to the approximately 40 min required for a handsewn anastomosis. The Vaso-Lock effectively maintained patency for at least 6 weeks without causing significant tissue damage. Histological analysis revealed that the device was successfully incorporated into the arterial wall, promoting a natural healing process. Additionally, organ evaluations indicated no adverse effects from using the Vaso-Lock. Our findings support the safety and effectiveness of the Vaso-Lock for arteriovenous anastomosis in pigs, with potential applicability for translation to humans. Our novel sutureless device has the potential to advance surgical practice and improve patient outcomes.

The extracellular matrix differentially directs myoblast motility and differentiation in distinct forms of muscular dystrophy: Dystrophic matrices alter myoblast motility.

Extracellular matrix (ECM) pathologic remodeling underlies many disorders, including muscular dystrophy. Tissue decellularization removes cellular components while leaving behind ECM components. We generated "on-slide" decellularized tissue slices from genetically distinct dystrophic mouse models. The ECM of dystrophin- and sarcoglycan-deficient muscles had marked thrombospondin 4 deposition, while dysferlin-deficient muscle had excess decorin. Annexins A2 and A6 were present on all dystrophic decellularized ECMs, but annexin matrix deposition was excessive in dysferlin-deficient muscular dystrophy. Muscle-directed viral expression of annexin A6 resulted in annexin A6 in the ECM. C2C12 myoblasts seeded onto decellularized matrices displayed differential myoblast mobility and fusion. Dystrophin-deficient decellularized matrices inhibited myoblast mobility, while dysferlin-deficient decellularized matrices enhanced myoblast movement and differentiation. Myoblasts treated with recombinant annexin A6 increased mobility and fusion like that seen on dysferlin-deficient decellularized matrix and demonstrated upregulation of ECM and muscle cell differentiation genes. These findings demonstrate specific fibrotic signatures elicit effects on myoblast activity.

A decade of PrEP: the evolution of HIV pre-exposure prophylaxis content and sentiments in South African print news media, 2012-2021.

After nearly a decade of HIV pre-exposure prophylaxis (PrEP) rollout in sub-Saharan Africa, there has been limited study of PrEP messaging in news media. We selected twenty South African newspapers with the highest circulation volumes to retrieve articles published in 2012-2021 mentioning PrEP (N = 249). Using inductive content analysis, we developed a structured codebook to characterise PrEP-related content and sentiments, as well as their evolution over time, in the South African press. Many articles espoused favourable attitudes towards PrEP (52%), but a sizeable fraction espoused unfavourable attitudes (11%). Relative to PrEP-favourable articles, PrEP-unfavourable articles were significantly more likely to emphasise the drawbacks/consequences of PrEP use, including adherence/persistence requirements (52% vs. 24%, p = .007), cost (48% vs. 11%, p < .001), and risk compensation (52% vs. 5%, p < .001). Nevertheless, the presence of these drawbacks/consequences in print media largely declined over time. Key populations (e.g. adolescents, female sex workers) were frequently mentioned potential PrEP candidates. Despite message variations over time, prevention effectiveness and adherence/persistence requirements were the most widely cited PrEP benefits and drawbacks, respectively. Study findings demonstrate the dynamic nature of PrEP coverage in the South African press, likely in response to PrEP scale-up and real-world PrEP implementation during the study period.

Heavy alcohol use and the HIV care continuum in Kenya: a population-based study.

Heavy alcohol use (HAU) can destabilize engagement along the HIV care continuum. Population-based studies assessing associations of HAU with HIV treatment outcomes are lacking, especially in sub-Saharan Africa. We leveraged data from the Kenya Population-based HIV Impact Assessment to identify associations of self-reported HAU, assessed using two items measuring the frequency and quantity of past-year alcohol consumption, with serum biomarkers for HIV serostatus unawareness, antiretroviral therapy (ART) non-use, and HIV viremia (≥1000 RNA copies/mL). Overall and sex-stratified survey-weighted logistic regression with jackknife variance estimation modeled adjusted odds ratios (adjOR) of HIV treatment indicators by HAU. Overall, 1491 persons living with HIV aged 15-64 years (68.4% female) were included. The prevalence of HAU was 8.9% (95% confidence interval [95%CI]: 6.8-11.0%) and was significantly more pronounced in males than females (19.6% vs. 4.0%, p < 0.001). In multivariable analysis, HAU was significantly (p < 0.001) associated with HIV serostatus unawareness (adjOR = 3.65, 95%CI: 2.14-6.23), ART non-use (adjOR = 3.81, 95%CI: 2.25-6.43), and HIV viremia (adjOR = 3.13, 95%CI: 1.85-5.32). Incorporating sex-specific alcohol use screening into HIV testing and treatment services in populations where HAU is prevalent could optimize clinical outcomes along the HIV care continuum.

Self-Reported Well-Being of Family Caregivers of Children with Medical Complexity.

OBJECTIVES: Provide an in-depth and psychometrically rigorous profile of the emotional well-being and sleep-related health of family caregivers of children with medical complexity (CMC). METHODS: Cross-sectional survey study of family caregivers of CMC receiving care from a pediatric complex care center between May 2021 and March 2022. Patient Reported Outcomes Measurement Information System Short-Forms (PROMIS-SF) assessed global mental health, emotional distress (anxiety, depression, anger), psychological strengths (self-efficacy, emotional regulation, meaning and purpose), and sleep-related health (fatigue, sleep-related impairment). Student's t-tests compared the sample's mean T-scores to US population norms. Pearson's correlation coefficient (ρ) examined associations between measures of psychological strengths and emotional distress. Unadjusted linear regression analyses explored relationships between well-being outcomes and child and caregiver characteristics. RESULTS: Compared to US population norms, caregivers of CMC (n = 143) reported significantly lower global mental health and emotional regulation ability as well as elevated symptoms of anxiety, depression, anger, fatigue, and sleep-related impairment (all p <.001). Whereas participants reported a significantly higher sense of meaning and purpose (p<.05), levels of self-efficacy were not significantly different from population norms. We observed moderate-to-strong inverse relationships between psychological strengths and emotional distress (ρ range, -0.39 to -0.69); with the strongest inverse associations found between emotional regulation ability and emotional distress. In exploratory analyses, caregiver race/ethnicity, socioeconomic status, and child health insurance type were significantly associated with caregiver well-being. CONCLUSION: Family caregivers of CMC report poor well-being, most notably, increased symptoms of anxiety and reduced global mental health and sleep-related health. WHAT'S NEW: In this cross-sectional survey of family caregivers of children with medical complexity, caregivers reported clinically significantly poorer global mental health, higher emotional distress, and reduced sleep-related health. This study provides potential therapeutic targets for future psychosocial interventions.

Community health worker outreach to farmworkers in rural North Carolina: Learning from adaptations to the SARS-CoV-2 pandemic.

BACKGROUND: Community health workers represent a critical part of the health outreach and services for migrant and seasonal farmworkers ('farmworkers') in rural areas of the United States. PURPOSE: We sought to identify adaptations to farmworker patient engagement and health outreach made by community health workers during the first 18 months of the COVID-19 pandemic. METHODS: In this qualitative study, we used semi-structured interviews with community health workers from August 2020 to February 2022 (n = 21). Two coders used thematic analysis to identify three themes related to the experiences of community health workers in conducting health education and outreach to farmworkers prior to and following the onset of the pandemic. FINDINGS: We found themes related to pre-pandemic outreach efforts to provide health education resource sharing with farmworkers and pandemic-related outreach efforts that included adoption of porch drops and distanced delivery of health education, adaptation of modes of health education and communication through technology and the internet, and taking on new roles related to COVID-19. Finally, we identified changes that reverted after the pandemic or will continue as adaptations. CONCLUSIONS: Community health workers created practice-based innovations in outreach in response to the COVID-19 pandemic. These innovations included new COVID-19 related roles and new modes of health education and outreach, including the use of digital resources. The changes developed for emergency use in COVID-19, particularly related to internet and technology, have likely altered how community health workers conduct outreach in North Carolina going forward. Funders, community health worker training programs, and researchers should take note of these innovations. PATIENT OR PUBLIC CONTRIBUTION: Community health workers who typically come from patient populations and provide critical navigation and connection with the health care system advised on the design and creation of this research project, including serving on an advisory board. Two authors have experience working as community health workers.

Multi-Institutional Bladder Exstrophy Consortium After 8 Years: The Short- and Intermediate-Term Outcomes.

PURPOSE: Bladder exstrophy (BE) poses challenges both during the surgical repair and throughout follow-up. In 2013, a multi-institutional BE consortium was initiated, which included utilization of unified surgical principles for the complete primary repair of exstrophy (CPRE), real-time coaching, ongoing video capture and review of video footage, prospective data collection, and routine patient data analysis, with the goal of optimizing the surgical procedure to minimize devastating complications such as glans ischemia and bladder dehiscence while maximizing the rate of volitional voiding with continence and long-term protection of the upper tracts. This study reports on our short-term complications and intermediate-term continence outcomes. MATERIALS AND METHODS: A single prospective database for all patients undergoing surgery with a BE epispadias complex diagnosis at 3 institutions since February 2013 was used. For this study, data for children with a diagnosis of classic BE who underwent primary CPRE from February 2013 to February 2021 were collected. Data recorded included sex, age at CPRE, adjunct surgeries including ureteral reimplantations and hernia repairs at the time of CPRE, osteotomies, and immobilization techniques, and subsequent surgeries. Data on short-term postoperative outcomes, defined as those occurring within the first 90 days after surgery, were abstracted. In addition, intermediate-term outcomes were obtained for patients operated on between February 2013 and February 2017 to maintain a minimum follow-up of 4 years. Outcomes included upper tract dilation on renal and bladder ultrasound, presence of vesicoureteral reflux, cortical defects on nuclear scintigraphy, and continence status. Bladder emptying was assessed with respect to spontaneous voiding ability, need for clean intermittent catheterization, and duration of dry intervals. All operating room encounters that occurred subsequent to initial CPRE were recorded. RESULTS: CPRE was performed in 92 classic BE patients in the first 8 years of the collaboration (62 boys), including 46 (29 boys) during the first 4 years. In the complete cohort, the median (interquartile range) age at CPRE was 79 (50.3) days. Bilateral iliac osteotomies were performed in 89 (97%) patients (42 anterior and 47 posterior). Of those undergoing osteotomies 84 were immobilized in a spica cast (including the 3 patients who did not have an osteotomy), 6 in modified Bryant's traction, and 2 in external fixation with Buck's traction. Sixteen (17%) patients underwent bilateral ureteral reimplantations at the time of CPRE. Nineteen (21%) underwent hernia repair at the time of CPRE, 6 of which were associated with orchiopexy. Short-term complications within 90 days occurred in 31 (34%), and there were 13 subsequent surgeries within the first 90 days. Intermediate-term outcomes were available for 40 of the 46 patients, who have between 4 and 8 years of follow-up, at a median of 5.7 year old. Thirty-three patients void volitionally, with variable dry intervals. CONCLUSIONS: Cumulative efforts of prospective data collection have provided granular data for evaluation. Short-term outcomes demonstrate no devastating complications, that is, penile injury or bladder dehiscence, but there were other significant complications requiring further surgeries. Intermediate-term data show that boys in particular show encouraging spontaneous voiding and continence status post CPRE, while girls have required modification of the surgical technique over time to address concerns with urinary retention. Overall, 40% of children with at least 4 years of follow-up are voiding with dry intervals of > 1 hour.

Acceptability of Event-Driven and Long-Acting HIV Pre-Exposure Prophylaxis Formulations Among Transgender Women Engaged in Street-Based Sex Work in Baltimore, Maryland.

We assessed acceptability of nonoral HIV pre-exposure prophylaxis (PrEP) formulations among transgender women (TW) engaged in street-based sex work in Baltimore, Maryland. In a K-means cluster analysis, TW (N=36) were partitioned into groups characterized by high interest in long-acting injectable PrEP only (Injectable Enthusiasts, 36%), high interest in injectables and subdermal implants (Long-Acting Acceptors, 36%), and low interest across PrEP formulations (Non-Acceptors, 28%). TW's interest in novel PrEP agents varied widely across formulations (range: 22-66%) and clustered around numerous relational, occupational, and structural factors, highlighting the importance of availing multiple PrEP formulations for this impacted population.

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative disorders characterized by hypoplasia and degeneration of the cerebellum and pons. We aimed to identify the clinical, laboratory, and imaging findings of the patients with diagnosed PCH with confirmed genetic analysis. We collected available clinical data, laboratory, and imaging findings in our retrospective multicenter national study of 64 patients with PCH in Turkey. The genetic analysis included the whole-exome sequencing (WES), targeted next-generation sequencing (NGS), or single gene analysis. Sixty-four patients with PCH were 28 female (43.8%) and 36 (56.3%) male. The patients revealed homozygous mutation in 89.1%, consanguinity in 79.7%, pregnancy at term in 85.2%, microcephaly in 91.3%, psychomotor retardation in 98.4%, abnormal neurological findings in 100%, seizure in 63.8%, normal biochemistry and metabolic investigations in 92.2%, and dysmorphic findings in 51.2%. The missense mutation was found to be the most common variant type in all patients with PCH. It was detected as CLP1 (n = 17) was the most common PCH related gene. The homozygous missense variant c.419G > A (p.Arg140His) was identified in all patients with CLP1. Moreover, all patients showed the same homozygous missense variant c.919G > T (p.A307S) in TSEN54 group (n = 6). In Turkey, CLP1 was identified as the most common causative gene with the identical variant c.419G > A; p.Arg140His. The current study supports that genotype data on PCH leads to phenotypic variability over a wide phenotypic spectrum.

Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform. The addition of CNV detection to exome analysis identified causal CNVs for 171 families (2.6%). The estimated sizes of CNVs ranged from 293 bp to 80 Mb. The causal CNVs consisted of 140 deletions, 15 duplications, 3 suspected complex structural variants (SVs), 3 insertions, and 10 complex SVs, the latter two groups being identified by orthogonal confirmation methods. To classify CNV variant pathogenicity, we used the 2020 American College of Medical Genetics and Genomics/ClinGen CNV interpretation standards and developed additional criteria to evaluate allelic and functional data as well as variants on the X chromosome to further advance the framework. We interpreted 151 CNVs as likely pathogenic/pathogenic and 20 CNVs as high-interest variants of uncertain significance. Calling CNVs from existing exome data increases the diagnostic yield for individuals undiagnosed after standard testing approaches, providing a higher-resolution alternative to arrays at a fraction of the cost of genome sequencing. Our improvements to the classification approach advances the systematic framework to assess the pathogenicity of CNVs.

Cesarean hysterectomy for placenta accreta spectrum: Surgeon specialty-specific assessment.

OBJECTIVE: To assess (i) clinical and pregnancy characteristics, (ii) patterns of surgical procedures, and (iii) surgical morbidity associated with cesarean hysterectomy for placenta accreta spectrum based on the specialty of the attending surgeon. METHODS: The Premier Healthcare Database was queried retrospectively to study patients with placenta accreta spectrum who underwent cesarean delivery and concurrent hysterectomy from 2016 to 2020. Surgical morbidity was assessed with propensity score inverse probability of treatment weighting based on surgeon specialty for hysterectomy: general obstetrician-gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. RESULTS: A total of 2240 cesarean hysterectomies were studies. The most common surgeon type was general obstetrician-gynecologist (n = 1534, 68.5%), followed by gynecologic oncologist (n = 532, 23.8%) and maternal-fetal medicine specialist (n = 174, 7.8%). Patients in the gynecologic oncologist group had the highest rate of placenta increta or percreta, followed by the maternal-fetal medicine specialist and general obstetrician-gynecologist groups (43.4%, 39.6%, and 30.6%, P < .001). In a propensity score-weighted model, measured surgical morbidity was similar across the three subspecialty groups, including hemorrhage / blood transfusion (59.4-63.7%), bladder injury (18.3-24.0%), ureteral injury (2.2-4.3%), shock (8.6-10.5%), and coagulopathy (3.3-7.4%) (all, P > .05). Among the cesarean hysterectomy performed by gynecologic oncologist, hemorrhage / transfusion rates remained substantial despite additional surgical procedures: tranexamic acid / ureteral stent (60.4%), tranexamic acid / endo-arterial procedure (76.2%), ureteral stent / endo-arterial procedure (51.6%), and all three procedures (55.4%). Tranexamic acid administration with ureteral stent placement was associated with decreased bladder injury (12.8% vs 23.8-32.2%, P < .001). CONCLUSION: These data suggest that patient characteristics and surgical procedures related to cesarean hysterectomy for placenta accreta spectrum differ based on surgeon specialty. Gynecologic oncologists appear to manage more severe forms of placenta accreta spectrum. Regardless of surgeon's specialty, surgical morbidity of cesarean hysterectomy for placenta accreta spectrum is significant.