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Background/Objective: Nonclassic congenital adrenal hyperplasia (NCCAH) may be overlooked or mistaken for polycystic ovarian syndrome. Unlike congenital adrenal hyperplasia (CAH), the enzymatic activities of 21-hydroxylase or 11β-hydroxylase in NCCAH are not completely lost. In this case, NCCAH presented in a patient with CYP21A2 and CYP11B1 heterozygous mutations, one of which is a variant of unknown significance in CYP11B1. Case Report: A 30-year-old woman presented with a chief complaint of irregular menses and hirsutism. Previous medical history was significant for a prolactin level of 34.7 ng/mL (reference range, 2.0-23.0 ng/mL), a total serum testosterone level of 77 ng/dL (reference range, 25-125 ng/dL, not sex-specific), and a 2-mm × 3-mm pituitary lesion. An adrenocorticotrophic hormone stimulation test increased the 17-hydroxyprogesterone level from 444 ng/dL at baseline to 837 ng/dL at 60 minutes (baseline female reference range and stimulated reference ranges are 10-300 ng/dL and

Excitation of long-lived states in bromine nuclei using a tabletop laser-plasma accelerator providing pulsed (<100  fs) electron beams provided a sensitive probe of γ strength and level densities in the nuclear quasicontinuum and may indicate angular momentum coupling through electron-nuclear interactions. Solid-density active LaBr&#95;{3} targets absorb real and virtual photons up to 35±2.5  MeV and deexcite through γ cascade into different states. A factor of 4.354±0.932 enhancement of the ^{80}Br^{m}/^{80}Br^{g} isomeric ratio was observed following electron irradiation, as compared to bremsstrahlung. Additional angular momentum transfer could possibly occur through nuclear-plasma or electron-nuclear interactions enabled by the ultrashort electron beam. Further investigation of these mechanisms could have far-reaching impact including decreased storage of long-term nuclear waste and an improved understanding of heavy element formation in astrophysical settings.

Background: The accuracy of low birth weight (LBW) and small for gestational age (SGA) in administrative healthcare records is crucial for perinatal studies but has few validity studies., Methods: Using 1999-2010 MAX linked to birth certificates (BC), we identified mother-infant dyads (≥30 days enrollment after delivery, with valid gestational age (GA) and birth weight (BW)). LBW and SGA were identified based on ICD-9-CM codes. Infants with BW <10% of the U.S. reference were flagged as SGA. For LBW group diagnoses, we imputed birthweight using median, mean BW from BCs, and ICD code boundaries of infants in the same LBW group. We calculated the sensitivity, specificity, and positive/negative predictive values to assess performance., Results: We identified 1,536,272 live births. All LBW groups had low SEs, high SPs, and NPVs, whereas PPVs varied. Among infants with SGA diagnoses based on GA/BW from the BC, SE of the SGA codes was 13.36%; SP 99.01%; PPV 67.37%. Combining imputation with LBW codes increased SE up to 22.09% (lower boundary) but decreased PPV to 41.53% (lower boundary)., Conclusions: ICD-9-CM codes from administrative healthcare records had low SE but high SP. Imputation based on GA and BW did not add much value to SGA identification., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess tablet utilization patterns and describe pre-treatment characteristics among new users of rimegepant., Background: Rimegepant is the only oral calcitonin gene-related peptide antagonist approved in the United States for both the acute and preventive treatment of migraine., Methods: We conducted a retrospective cohort study of people with migraine who initiated treatment with rimegepant using two US commercial claims databases (MarketScan and Optum). Patients (≥18 years old) with migraine who newly initiated rimegepant were included. Patients were stratified into two groups representing acute (quantity = 8) and prevention (quantity = 15 or 16) use cohorts. Baseline characteristics and medication use history were assessed on index and during the 365-day pre-index period. Rimegepant utilization periods were calculated based on days supplied and varying approaches to define use periods. Tablet quantity per 30 days was reported separately for both acute and prevention cohorts., Results: In MarketScan, a total of 14,037 rimegepant users were identified; 11,195 (79.8%) in the acute group and 1,880 (13.4%) in the prevention group. Rimegepant utilization for acute use was 4.9 ± 2.1 tablets per 30 days and for preventive use was 13.1 ± 7.7 tablets per 30 days. There was high baseline prevalence of triptan contraindications, warnings, and high cardiovascular risk, with a combined 46.2% meeting one or more of these criteria. Acute medication overuse was also common (25.1%) prior to rimegepant initiation. Results were consistent in the Optum database., Conclusion: Our analysis provides the first real-world data available on tablet utilization and characteristics of new users of rimegepant.

Aim: To examine the associations between low cognitive performance (LCP) and diabetes-related health indicators (including body mass index [BMI], HbA1c, systolic blood pressure [SBP], low-density lipoprotein [LDL] and self-reported poor physical health) and whether these associations vary across racial/ethnic subgroups., Methods: We identified adults aged 60 years or older with self-reported diabetes from the 2011-2014 National Health and Nutrition Examination Survey. Individuals with cognitive test scores in the lowest quartile were defined as having LCP. We used regression models to measure the associations of LCP with diabetes-related biometrics (BMI, HbA1c, SBP and LDL); and self-reported poor physical health. Moreover, we explored potential variations in these associations across racial/ethnic subgroups., Results: Of 873 (261 with LCP) adults with diabetes, LCP was associated with higher HbA1c, SBP and LDL (adjusted difference: 0.41%, 5.01 mmHg and 5.08 mg/dL, respectively; P < .05), and greater odds of reporting poor physical health (adjusted odds ratio: 1.59, P < .05). The association between LCP and HbA1c was consistent across racial/ethnic groups, and notably pronounced in Hispanic and Other. BMI worsened with LCP, except for non-Hispanic Black. Excluding the Other group, elevated SBP was observed in people with LCP, with Hispanic showing the most significant association. LDL levels were elevated with LCP for Hispanic and Other. Physical health worsened with LCP for both non-Hispanic Black and Hispanic., Conclusions: We quantified the association between LCP and diabetes-related health indicators. These associations were more pronounced in Hispanic and Other racial/ethnic groups., (© 2024 John Wiley & Sons Ltd.)

Background: Despite their frequent concurrent use, little is known about the concomitant use of calcium channel blockers (CCBs) and selective serotonin reuptake inhibitors (SSRIs) on fracture risk. We compared risk of fractures in patients concomitantly treated with CCBs and SSRIs versus CCB-only users. We compared risk of fractures among concomitant CCB-SSRI users initiating cytochrome P450 3A4 (CYP3A4)-inhibiting SSRIs versus non-CYP3A4 inhibiting SSRIs., Methods: This retrospective cohort study used IBM MarketScan commercial claims and Medicare Supplemental database (2007-2019). We included adults diagnosed with hypertension and depression, newly initiating SSRIs while being treated with CCBs (ie, concomitant CCB-SSRI users) and those who did not (ie, CCB-only users). Primary outcome was the first occurrence of any fracture. We used stabilized inverse probability of treatment weighting (sIPTW) based on propensity scores to balance baseline risk between groups. Cox proportional hazard regression modeling was used to compare fracture risk., Results: We identified 191 352 concomitant CCB-SSRI and 956 760 CCB-only users (mean age = 56 years, 50.1% males). After sIPTW, compared with CCB-only users, CCBs-SSRIs users had a higher risk of fractures (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.22-1.66). No difference in the risk of fractures between concomitant users of CCB-CYP3A4-inhibiting SSRIs and those of CCB-non-CYP3A4 inhibiting SSRIs (HR: 1.10, 95% CI: 0.87-1.40) was observed., Conclusion and Relevance: Short-term concomitant CCB-SSRI use was associated with increased fracture risk. Concomitant CCBs and CYP3A4-inhibiting SSRIs compared with CCBs and non-CYP3A4 inhibiting SSRIs use was not associated with increased risk., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Park has received grant funding from Bristol Myers Squibb. None of these are relevant to this study. The remaining authors report no conflicts of interest.

Introduction Acute cholecystitis is a common complication of gallstone disease. Likewise, gallbladder necrosis is a complication of cholecystitis associated with higher risks of morbidity and mortality. Identification of risk factors which portend to gallbladder necrosis is key in prioritizing the management of higher-risk patients. This study aimed to identify such factors that predict the development of gallbladder necrosis. Method A retrospective review of all patients undergoing emergency cholecystectomy in a tertiary hospital over a two-year period was performed. Gallbladder necrosis was diagnosed on histopathological examination of operative specimens. Multivariable logistic regression was performed to determine risk factors for gallbladder necrosis. Results A total of 163 patients underwent acute cholecystectomy and 43 (26%) had proven gallbladder necrosis. Multivariable analysis demonstrated that elevated white cell count (WCC) (OR 1.122, 95%CI 1.031-1.221, p=0.007), elevated C-reactive protein (CRP) (OR 1.004, 95%CI 1.001-1.008, p=0.022) and positive smoking status (OR 5.724, 95%CI 1.323-24.754, p=0.020) were independently predictive of gallbladder necrosis. Notably, advancing age, elevated BMI, diabetes mellitus or American Society of Anesthesiologists (ASA) grade were not found to be associated with developing necrosis. Conclusion Patients at risk of gallbladder necrosis include those with higher WCC, CRP, and active smokers. Given the increased potential complications, these risk factors should be identified early in the management of those admitted with gallstone disease to ensure such patients receive aggressive medical therapy alongside timely and guided surgical intervention., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Maharajh et al.)

Physical interaction with patients, for example conducted as part of a diagnostic examination or surgical procedure, provides clinicians with a wealth of information about their condition. Simulating this interaction is of great interest to researchers in both haptics and medical education, and the development of softness changing tactile interfaces is important in recreating the feel of different soft tissues. This paper presents designs for a variety of novel electromechanical and electromagnetic mechanisms for controlling particle jamming-based, hardness changing tactile displays, intended to allow medical trainees to experience these physical interactions in a range of simulation settings such as clinical skills teaching laboratories. Each design is then subjected to a battery of mechanical tests to evaluate its effectiveness compared to the state of the art, as well as their suitability for simulating the physical hardness of different types of soft tissues, previously characterised in established literature. These results demonstrate that all of the technologies presented are able to exhibit a measurable hardness change, with Shore hardness values between 3A and 57A achieved by the most effective constriction-based device. The electromechanical devices based on constriction and compression, and the state-of-the-art pneumatic device, were able to achieve hardness changes within a range that is useful for replicating the softness of organic tissue. The electromechanical and electromagnetic devices were also found to effect their full range of hardness change in less than a second, compared to several seconds for the state-of-the-art. These results show that the performance of softness changing tactile displays can be improved with the electromechanical actuation techniques proposed in this paper, and that such displays are able to replicate the physical characteristics of soft tissues and may therefore be of benefit in medical training and simulation scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Brown and Bello.)

Purpose: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs., Methods: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs., Results: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants., Conclusions: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based., (© 2024 John Wiley & Sons Ltd.)

Purpose: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology., Methods: To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert-based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group., Results: Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary., Conclusions: While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Introduction: Outcomes following esophagectomy for esophageal cancer have continued to improve over the last 30 years. Post-operative complications impact upon peri-operative and short-term survival but the effect on long-term survival remains debated. This study aims to investigate the effect of post-operative complications on long-term survival following esophagectomy., Materials and Methods: All patients who underwent an esophagectomy between January 2010 and January 2019 were included from a single high-volume center. Data was collected contemporaneously. Patients were separated into three groups; those who experienced no, or very minor complications (Clavien-Dindo 0 or 1), minor complications (Clavien-Dindo 2), and major complications (Clavien-Dindo 3-4), at 30 days. To correct for short-term mortality effects, those who died during the index hospital admission were excluded. Overall survival was analyzed using Kaplan-Meier and log rank testing., Results: The study cohort comprised 721 patients. There were 42.4% (306/721), 29.5% (213/721) and 25.7% (185/721) in the Clavien-Dindo 0-1, Clavien-Dindo 2, and Clavien-Dindo 3-4 group respectively. Seventeen patients (2.4%) died during their index hospital admission and were therefore excluded. There was no significant difference between median survival across the 3 groups (50, 57 and 52 months). Across all 3 groups, overall long-term survival rates were equivalent at 1 (87.5%, 84.9%, 83.2%), 3 (59.7%, 59.6%, 54.2%), and 5 years (43.9%, 48.9%, 45.7%) (p = 0.806). The only factors independently associated with survival in this cohort, were male gender, Charlson comorbidity index, and overall pathological stage of disease., Conclusion: Long-term survival is not affected by peri-operative complications, irrespective of severity, following esophagectomy. Further study into the long-term quality of life is required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Corticosteroids are essential to curative acute lymphoblastic leukemia (ALL) treatment, yet have significant neuropsychiatric side effects that decrease quality of life for patients and families. We conducted a scoping review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to describe the existing measurement tools used to evaluate neurobehavioral side effects of corticosteroids in pediatric ALL. From various databases and registers, 4047 studies were identified. Twenty-four articles met inclusion criteria. Clinical assessment was most used to evaluate these symptoms. Twelve validated measures were identified. Existing data about neuropsychiatric side effects of corticosteroids in pediatric ALL are extremely heterogeneous, creating challenges for standardized assessment and management., (© 2024 Wiley Periodicals LLC.)

Aims: To quantify the incremental health and economic burden associated with cognitive impairment (CI) among non-institutionalized people with diabetes ≥65 years in the United States., Materials and Methods: Using 2016-2019 Medical Expenditure Panel Surveys data, we identified participants ≥65 years with diabetes. We used propensity score weighting to quantify the CI-associated incremental burden on health-related quality of life measured by the 12-item Short Form Survey (SF-12), including the mental component summary score, physical component summary score and health utility. We also compared the annual health service utilization and expenditures on ambulatory visits, prescriptions, home care, emergency room (ER), hospitalizations and total annual direct medical expenditures., Results: We included 5094 adults aged ≥65 with diabetes, of whom 804 had CI. After propensity score weighting, CI was associated with a lower mental component summary score (-8.4, p < .001), physical component summary score (-5.2, p < .001) and health utility (-0.12, p < .001). The CI group had more ambulatory visits (+4.4, p = .004) and prescriptions (+9.9, p < .001), with higher probabilities of having home care (+11.3%, p < .001) and ER visits (+8.2%, p = .001). People with CI spent $5441 (p < .001) more annually, $2039 (p = .002) more on prescriptions, $2695 (p < .001) more on home care and $118 (p < .001) more on ER visits. There is no statistically significant difference in the utilization and expenditure of hospitalizations., Conclusion: CI was associated with worse health-related quality of life, higher health service utilization and expenditures. Our findings can be used to monitor the health and economic burden of CI in non-institutionalized older persons with diabetes., (© 2023 John Wiley & Sons Ltd.)

Introduction: The handheld fan ('fan') is useful for chronic breathlessness management, however little is known about clinicians' implementation of the fan in clinical practice., Aim: To explore clinicians' experiences and views of fan implementation., Methods: A qualitative approach, using semi-structured interviews. Participants were purposively sampled from clinicians who had completed an on-line fan implementation survey and were willing to participate. A topic guide was developed using the Theoretical Domains Framework (TDF). Data were analysed using an inductive approach informed by the TDF., Findings: Twelve clinicians participated (doctors n = 4; nurses n = 4; allied health professionals n = 4) from respiratory and palliative care. Analysis generated three major themes: i) Clinician knowledge and skills in fan implementation, ii) environmental constraints on fan use and iii) clinician beliefs about the consequences of fan use. Implementation by clinicians was positively influenced by having a scientific rationale for fan use presented (mechanism of action). Clinicians believed that the fan relieved breathlessness and did not carry a significant infection risk. Opportunity for fan use varied across healthcare settings; key environmental influences were COVID-19 restrictions, lack of access to resources and funding to provide fans, particularly in acute and respiratory services. Clinicians commonly encountered scepticism among patients and colleagues who felt the fan was an implausible intervention for breathlessness., Conclusion: Implementation of the fan is motivated by clinician beliefs about patient-benefit, a scientific rationale to counter clinician and patient scepticism, and access to fans in clinic. Funding to allow patients to be supplied with and taught how to use a fan would support uptake. Research is needed to address concerns about infection risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Brown et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

While opioid prescribing has significantly decreased from a peak in 2012, less is known about the national utilization of non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP) in the context of the opioid crisis. The objective of this study is to characterize the prescribing trends of NSAIDs and APAP in the US ambulatory care setting. We conducted repeated cross-sectional analyses using the 2006-2016 National Ambulatory Medical Care Survey. NSAID-involved visits were defined as patient visits among adults in which NSAIDs were ordered, supplied, administered, or continued. We used similarly-defined APAP visits as a referent group for context. After excluding aspirin and other NSAID/APAP combination products containing opioids, we calculated the annual proportion of NSAID-involved visits among all ambulatory visits. We conducted trend analyses using multivariable logistic regression adjusted for years, patient, and prescriber characteristics. From 2006 to 2016, there were 775.7 million NSAID-involved visits and 204.3 million APAP-involved visits. Most NSAIDs-involved visits were from patients aged 46-64 years (39.6%), female (60.4%), White (83.2%), and having commercial insurance (49.0%). There were significant increasing trends for the proportion of NSAID-involved visits (8.1-9.6%) and APAP-involved visits (1.7-2.9%) (both P < .0001). We observed an overall increase in NSAID and APAP-involved visits in US ambulatory care settings from 2006 to 2016. This trend may be attributed to decreasing opioid prescribing and raises safety concerns related to acute or chronic NSAID and APAP use. PERSPECTIVE: This study shows an overall increasing trend in NSAID use reported in nationally representative ambulatory care visits in the United States. This increase coincides with previously reported significant decreases in opioid analgesic use, particularly after 2012. Given the safety concerns related to chronic or acute NSAID use, there is a need to continue monitoring the use trends of this class of medication., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Current clinical practice guidelines (CPG) recommend periodic pressure redistribution (PR) to alter sitting pressure and reduce the risk of developing pressure injuries (PI). Individuals who have strength and trunk stability are asked to perform PR such as wheelies, leaning laterally, and forward-leaning to minimize the duration of pressure acting on the same region of the body., Objective: Our long-term objective is to build upon previous research and development to create a more effective device for improving PR training and adherence to CPG among manual wheelchair users (MWU). Through this study, we employed a participatory action design and engineering (PADE) approach in developing the hardware and user interface to increase the likelihood of eventually yielding a device effective for both MWU and clinicians., Participants: Focus Groups : Ten clinicians - 6 physical therapists, 3 occupational therapists, and one registered nurse, and 10 MWU with spinal cord injuries (SCI) who reported using their wheelchairs 40-80 h per week. Five-Day Assessment : Five male MWU with SCI who had been wheelchair users for 18.5 ± 16.2 years. Four-Week Investigation : The 7 participants with SCI were 5 males and 2 females, who had been wheelchair users for 24.7 ± 17.0 years., Methods: A PADE approach was used to improve upon a manual wheelchair virtual coaching system for people with SCI. The system comprises a seat support instrumented with force sensors, software algorithms to detect PR, and a smart phone app for user interface. The methods included three stages: multiple focus groups, a five-day evaluation phase with participants using their own wheelchairs in their homes and communities, and a 4-week assessment with improvements made based on the 5-day results by users with their own wheelchairs in their homes and communities., Results: The focus groups yielded guidance for ergonomics, user interface, charging frequency, and key dimensions and mass. The 5-day study identified mechanical, electrical, and connectivity challenges, which were resolved before the 4-week study. The 4-week trial suggested that participants performed PR less frequently than clinically recommended and provided an indication of the types of maneuvers that they performed., Conclusion: A prototype manual wheelchair virtual coaching system was developed using a PADE process. The system was able to detect and record PR in home and community environments. Following improvements identified in this study, a future version will be tested with additional users to determine whether it can improve adherence to PR guidance.

Background: Preclinical studies have suggested potential beneficial effects of newer glucose-lowering drugs (GLDs) including dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors, in protecting humans against cognitive decline and dementia. However, population studies aiming to demonstrate such cognitive benefits from newer GLDs have produced mixed findings. This meta-analysis aimed to evaluate the association between newer GLDs and risk of dementia in adults with type 2 diabetes (T2D)., Methods: Electronic databases were searched up to March 11, 2022 to include observational studies that examined the association between DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors and risk of dementia (including all-cause dementia, Alzheimer's disease [AD], and vascular dementia [VD]) in people with T2D. We conducted a random-effects meta-analysis to calculate the relative risk (RR) with 95% confidence interval (CI) for each class of newer GLD., Results: Ten studies (from nine articles) involving 819,511 individuals with T2D were included. Three studies found that SGLT2 inhibitor users had a lower risk of all-cause dementia than non-SGLT2 inhibitor users (RR, 0.62; 95% CI, 0.39-0.97). Five studies found that users versus nonusers of GLP-1RAs were associated with a significant reduction in the risk of all-cause dementia (RR, 0.72; 95% CI, 0.54-0.97). However, a meta-analysis for AD and VD was unavailable for SGLT2 inhibitors and GLP-1RAs because only one study was included for each drug. In seven studies, users vs. nonusers of DPP-4 inhibitors were significantly associated with a decreased risk of all-cause dementia (RR, 0.84; 95% CI, 0.74-0.94) and VD (RR, 0.59; 95% CI, 0.47-0.75) but not AD (RR, 0.82; 95% CI, 0.63-1.08)., Conclusion: Newer GLDs were associated with a decreased risk of all-cause dementia in people with T2D. Because of the observational nature and significant heterogeneity between studies, the results should be interpreted with caution. Further research is warranted to confirm our findings., (© 2023 The American Geriatrics Society.)

The actin cytoskeleton plays a critical role in cancer cell invasion and metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate cancer cell invasion by focusing the secretion of extracellular matrix-degrading enzymes, including matrix metalloproteinases (MMPs). In this study, we investigated the nuclear role of cysteine-rich protein 2 (CRP2), a two LIM domain-containing F-actin-binding protein that we previously identified as a cytoskeletal component of invadopodia, in breast cancer cells. We found that F-actin depolymerization stimulates the translocation of CRP2 into the nucleus, resulting in an increase in the transcript levels of pro-invasive and pro-metastatic genes, including several members of the MMP gene family. We demonstrate that in the nucleus, CRP2 interacts with the transcription factor serum response factor (SRF), which is crucial for the expression of MMP-9 and MMP-13 . Our data suggest that CRP2 and SRF cooperate to modulate of MMP expression levels. Furthermore, Kaplan-Meier analysis revealed a significant association between high-level expression of SRF and shorter overall survival and distant metastasis-free survival in breast cancer patients with a high CRP2 expression profile. Our findings suggest a model in which CRP2 mediates the coordination of cytoplasmic and nuclear processes driven by actin dynamics, ultimately resulting in the induction of invasive and metastatic behavior in breast cancer cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mgrditchian, Brown-Clay, Hoffmann, Müller, Filali, Ockfen, Mao, Moreau, Casellas, Kaoma, Mittelbronn and Thomas.)

Objective: To evaluate the association of concomitant topiramate and oral hormonal contraceptive use with unintended pregnancies., Study Design: We conducted a retrospective cohort design in MarketScan Research Databases (2005-2018) on women aged 12-48 who had migraines or chronic headaches and concomitantly used topiramate and oral contraceptives. We used a cohort of patients with oral contraceptives and concomitant use of other migraine prevention therapies (propranolol, metoprolol, amitriptyline, venlafaxine, or verapamil) as a comparator. We followed patients for up to 1 year from cohort entry to assess the occurrence of unintended pregnancy (i.e., contraception failure). Pregnancy events were measured via an algorithm harnessing medical encounters information with live births, terminations, or prenatal visits. Statistical models accounted for multiple cohort entries and adjusted for measured confounders via a propensity score weighting method., Results: We identified 63,649 episodes of oral contraceptives+topiramateand 59,012 episodes of oral contraceptives+other maintenance therapies. The mean age was 29.2±9.0 and 29.0±9.3 years in the study cohorts. In the adjusted analysis, the contraception failure rate (95% confidence interval) was 1.3 (1.1, 1.6) per 100 person-years in the oral contraceptives+topiramate cohort and 1.3 (1.1, 1.6) in the oral contraceptives+other maintenance therapies cohort. The adjusted rate ratio and rate difference measures were 1.00 (0.80, 1.26) and 0.00 (-0.3, 0.3)., Conclusion: Concomitant use of low-dose topiramate and oral contraceptives among patients with migraines was not associated with a higher risk for unintended pregnancies., Implications: Our real-world findings confirm clinical pharmacology trials, suggesting that low-dose (≤200 mg/d) topiramate may not influence oral contraceptive effectiveness., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The 2019 coronavirus (COVID-19) pandemic led to stay-at-home (SAH) orders in Pennsylvania targeted at reducing viral transmission. Limitations in population mobility under SAH have been associated with decreased motor vehicle collisions (MVC) and related injuries, but the impact of these measures on severity of injury remains unknown. The goal of this study is to measure the incidence, severity, and outcomes of MVC-related injuries associated with SAH in Pennsylvania., Materials & Methods: We conducted a retrospective geospatial analysis of MVCs during the early COVID-19 pandemic using a state-wide trauma registry. We compared characteristics of patients with MVC-related injuries admitted to Pennsylvania trauma centers during SAH measures (March 21-July 31, 2020) with those from the corresponding periods in 2018 and 2019. We also compared incidence of MVCs for each zip code tabulation area (ZCTA) in Pennsylvania for the same time periods using geospatial mapping., Results: Of 15,550 trauma patients treated during the SAH measures, 3486 (22.4%) resulted from MVCs. Compared to preceding years, MVC incidence decreased 10% under SAH measures with no change in mortality rate. However, in ZCTA where MVC incidence decreased, there was a 16% increase in MVC injury severity., Conclusions: Stay-at-home orders issued in response to the COVID-19 pandemic in Pennsylvania were associated with significant changes in MVC incidence and severity. Identifying such changes may inform resource allocation decisions during future pandemics or SAH events.

Introduction: Surgical risk calculators have expanded in both number and sophistication of their predictive approach. These calculators are gaining popularity as validated tools to help surgeons estimate mortality and complications following emergency general surgery (EGS). However, the accuracy of risk estimates generated by these calculators compared to risk estimation by practicing surgeons has not been explored., Methods: Acute care surgeons at a quaternary care center prospectively estimated 30-d mortality and complications for adult EGS patients (2019-2021). Surgeon predictions were compared to Predictive OpTimal Trees in Emergency Surgery Risk (POTTER) and NSQIP estimates. Observed-to-expected (O:E) ratios of median aggregate estimates were calculated. C-statistics for surgeon and calculator estimations were utilized to quantify predictive accuracy., Results: Among 150 patients (median 61 y, 45% male), 30-d mortality was 15% (n = 23). Observed rates of prolonged mechanical ventilation and acute renal failures were 30% and 10%, respectively. Overall, surgeon predictions were similar to risk calculator estimates for mortality (c-statistics 0.843 [surgeon] versus 0.848 [POTTER] and 0.815 [NSQIP]) and need for prolonged ventilation (c-statistics 0.801 versus 0.722 and 0.689, respectively). Surgeons tended to overestimate complication risks. Surgeon experience was not significantly associated with mortality prediction in an adjusted model., Conclusions: Acute care surgeons at a quaternary care center predicted postoperative mortality and complications with similar discrimination when compared to surgical risk calculators. Surgeon expertise should be utilized in conjunction with risk calculators when counseling EGS patients regarding anticipated postoperative outcomes. Surgeons should be cognizant of patterns in overestimation or underestimation of complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Appendiceal cancer with peritoneal metastases (ACPM) is a complex disease requiring multidisciplinary care. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can significantly improve survival but requires evaluation by a surgical oncologist and significant treatment endurance. The impacts of socioeconomic status (SES) and other social determinants of health on rates of surgical evaluation and treatment have not been examined., Methods: We conducted a retrospective cohort study examining all patients with ACPM from 2010 to 2018 in a regional healthcare system. Patient characteristics, oncologic details, treatment strategies, and survival were examined. The primary outcomes of interest were referral to Surgical Oncology, receipt of CRS HIPEC, and survival., Results: Of 194 patients identified, 94% had synchronous ACPM. The majority of patients (95%) were referred to surgical oncology. Advanced age was the only predictor of nonreferral (p < 0.001). A total of 147 patients (76%) ultimately underwent CRS HIPEC. After adjusting for medical and tumor characteristics, CRS HIPEC was less likely for patients who were unmarried [odds ratio (OR) 0.253, p = 0.004] or of low SES (OR 0.372, p = 0.03). On subanalysis of patients undergoing CRS HIPEC, median overall survival was worse for patients of low SES [51 months versus not reached (NR), p = 0.05], and this disparity persisted on multivariate analysis [hazard ratio (HR) = 2.278, p = 0.001]., Conclusions: This analysis is the first to evaluate barriers to CRS HIPEC for ACPM. While most patients were evaluated by a multidisciplinary team, nonmedical factors may play a role in the treatment received and ultimate outcomes. Addressing these disparities is crucial for ensuring equitable outcomes and improving patient care., (© 2022. Society of Surgical Oncology.)

This paper presents the design and experimental characterisation of a wrist haptic interface based on a twisted string actuator. The interface is designed for controlled actuation of wrist flexion/extension and is capable of rendering torque feedback through a rotary handle driven by the twisted string actuator and spring-loaded cable mechanisms. The interface was characterised to obtain its static and dynamic haptic feedback rendering capabilities. Compliance in the spring and actuation mechanism makes the interface suitable for smooth rendering of haptic feedback of large magnitudes due to the high motion transmission ratio of the twisted strings. Haptic virtual wall rendering capabilities are demonstrated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Skvortsova, Nedelchev, Brown, Farkhatdinov and Gaponov.)

Background: Native American newborns experience high rates of prenatal drug exposure leading to devastating outcomes within Indigenous communities. Such children are at heightened risk of maladaptive outcomes if early intervention does not occur. A need exists to identify strategies that promote resilience., Objectives: Identify barriers and facilitators that families experience in family-child engagement activities across the community, culture, outdoors, and home settings to inform a cultural-sensitive and community-relevant study aimed at quantifying positive family-child engagement activities as a resilience factor in this population., Methods: Biological parents and caregivers to children, ages 0-3 years old with or without prenatal drug exposure (N = 15) were recruited from the Confederated Salish and Kootenai Tribes to participate in an in-person semi-structured interview. Data analysis consisted of research yarning and directed content analysis to collect unique stories and to identify common activities, barriers, supports and positive outcomes to families, respectively., Results: Attending multiple powwows/celebrations, swimming, and reading were the most mentioned activities. Cost and transportation were common barriers. The most common support mechanism provided was having family or friends present to participate in activities. Cultural knowledge and bonding were common positive outcomes for a child engaging in activities. A collection of stories identified both familial barriers to traditional ways of knowing and participation in community, and community-implemented efforts to bridge that gap among families with a history of drug and alcohol use., Conclusions: This study identifies potential resilience factors specific to families to children with prenatal drug exposure that reside in Indigenous communities., Competing Interests: The authors have declared that no competing interests exist.

Background/purpose: Decompressive laparotomy and open abdomen for abdominal compartment syndrome have been historically avoided during Extracorporeal Membrane Oxygenation (ECMO) due to seemingly elevated risks of bleeding and infection. Our goal was to evaluate a cohort of pediatric respiratory ECMO patients who underwent decompressive laparotomy with open abdomen at a single institution and to compare these patients to ECMO patients without open abdomen., Methods: We reviewed all pediatric respiratory ECMO (30 days-18 years) patients treated with decompressive laparotomy with open abdomen at Riley Hospital for Children (1/2000-12/2019) and compared these patients to concurrent respiratory ECMO patients with closed abdomen. We excluded patients with surgical cardiac disease. We assessed demographics, ECMO data, and outcomes and defined significance as p = 0.05., Results: 6 of 81 ECMO patients were treated with decompressive laparotomy and open abdomen. Open and closed abdomen groups had similar age (p = 0.223) and weight (0.286) at cannulation, but the open abdomen group had a higher reliance on vasoactive medications (Vasoactive Inotropic Score, p = 0.040). Open abdomen group survival was similar to closed abdomen patients (66.7%, vs 62.7%, p = 1). Open abdomen patients had lower incidence of ECMO complications (33.3% vs 83.6%, p = 0.014), but the groups had similar bleeding complications (p = 0.412) and PRBC transfusion volume (p = 0.941)., Conclusion/impact: Pediatric ECMO patients with open abdomen after decompressive laparotomy had similar survival, blood products administered, and complications as those with a closed abdomen. An open abdomen is not a contra-indication to ECMO support in pediatric respiratory patients and should be considered in select patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Laryngotracheal reconstruction (LTR) is a complex operation used to treat subglottic stenosis. The use of simulator models is a valuable tool in surgical trainee education, particularly for operations such as LTR that are less common outside high-volume centers. Three-dimensional (3D) printing of the human airway may provide an effective and more accessible alternative to porcine cadaveric models. The objective of this study is to compare the educational value of a 3D-printed model and a porcine cadaveric model as LTR simulation methods., Methods: Simulated LTR procedures were completed by 12 otolaryngology residents and a faculty physician on the cadaveric model and the 3D-printed simulator model. Both models were evaluated by fellowship-trained pediatric otolaryngologists to establish construct validity. Pre-procedure surveys of participants evaluated confidence and attitude toward models and post-procedure surveys evaluated confidence, overall impressions, relevance, content validity, and face validity., Results: Participants reported a similar mean increase in confidence after performing LTR on the 3D-printed model (14%) and cadaveric model (11%). Participants rated both models similarly for utility as an overall training tool and in teaching surgical planning and improving operative techniques. However, participants found the 3D-printed model more useful for teaching anatomy ( p  = .047)., Conclusion: 3D-printed models have practical benefits over cadaveric models; they do not decompose and can be custom made to model a disease state such as subglottic stenosis. Participants reported a similar mean increase in confidence after using either simulation. The 3D-printed model is a promising simulation candidate as it compares well to an animal model and has the advantage of being more anatomically true to pediatric patients.Level of Evidence: Level 2., Competing Interests: The authors have no conflicts of interest to disclose. David Zopf is a cofounder of University of Michigan affiliated startup MakeMedical LLC, which provided no financial support for the research., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)