Search

Objective: The authors sought to quantify the role of social media-related academic activity through use of the Altmetric score (a composite score based on social media attention from a variety of sources) and investigate its potential impact on the number of citations received at 3 years postpublication (articles published between January 2019 and December 2019)., Methods: Articles published in the top 12 neurosurgical journals according to Google Scholar (based on 5-year Web of Science impact factors, 2017-2021) were identified. Data collected included days since publication, Altmetric scores, and total number of tweets (posts), and 3-year citations were obtained from Google Scholar. A multiple linear regression model was created that featured a blocking method to stratify confounding variables from most to least contributing. Furthermore, the data were dichotomized by publications with ≥ 10 citations (top 25th percentile) and those with < 10 to analyze the impact of the score on total number of citations received at 3 years, using an independent-samples Mann-Whitney U-test., Results: Among 6721 included articles, the mean Altmetric score was 3.76 ± 15.69 and the mean number of citations received was 9.61 ± 22.16. When accounting for relevant control variables, the Altmetric score was a significant predictor of the total number of citations accumulated at 3 years (variability of 10.17%). On statistical testing, the Altmetric score was significantly higher in publications with ≥ 10 citations (p < 0.001)., Conclusions: The authors report a strong, statistically significant correlation between the Altmetric score and the number of citations received. To their knowledge, this is the first study to demonstrate the impact of social media academic activity on neurosurgery article citation dissemination, potentially influencing resident medical education.

Case Summary: A 6-month-old male entire domestic shorthair cat presented for presumptive Toxoplasma myopathy that was non-responsive to antiprotozoal therapy. Clinical features included marked macroglossia, dysphagia, regurgitation, truncal muscle hypertrophy, pelvic limb gait abnormalities and megaoesophagus. Relevant diagnostics included serial creatine kinase activity, cardiac troponin I, fluoroscopic swallow study and routine muscle histopathology. Ultimately, post-mortem histopathology with immunostaining demonstrated markedly decreased or absent staining for the rod and carboxy terminus of dystrophin, confirming a dystrophin-deficient muscular dystrophy (MD). The misdiagnosis of toxoplasmosis was based on an increased IgG titre and muscle histopathology submitted to a local laboratory. Treatment for megaoesophagus included vertical feeding of wet food only, sildenafil and omeprazole. Dysphagia and regurgitation improved moderately. Presumptive hyperaesthesia and muscle pain were managed with anti-inflammatory doses of prednisolone. The patient was ultimately euthanased as a result of progressive MD signs and uraemia at 2 years of age., Relevance and Novel Information: This case report highlights the collective clinical features of MD, as they could be considered pathognomonic for this rare condition and must be differentiated from other myopathies via specific immunostaining of muscle biopsies. This is crucial to obtain a correct and early diagnosis, allowing instigation of potentially valuable treatments. Megaoesophagus is an inconsistent feature in feline MD in addition to the more commonly observed oropharyngeal dysphagia. Management with a canned diet, sildenafil, omeprazole and upright feeding was beneficial with moderate improvement in the frequency of regurgitation. Prednisolone was thought to minimise the presumptive myalgia., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: The objective of this study was to investigate the diagnostic potential of bacterial biomarkers by comparing the performance of molecular detection assays with clinical assessments of dog's oral health performed by veterinarians., Methods: Supragingival and subgingival plaque samples were collected from 127 client-owned dogs, pre-booked for procedures under general anesthesia, visiting veterinary practices in the United States. DNA was extracted and bacterial biomarkers quantified using quantitative polymerase chain reaction. Gingivitis and periodontitis were recorded by a trained clinician using the Weighted Gingivitis Periodontitis Score which involved assessing the buccal surfaces of 18 teeth while under general anesthesia. Intraoral dental radiographs of the left and right mandibular first molar teeth were also obtained. These data were then used to establish the diagnostic performance of the molecular assay to detect periodontitis., Results: An initial conscious, visual oral examination performed by the veterinarian identified 67.7% of dogs as having periodontitis, but examination under general anesthesia indicated a higher proportion (86.6%). Analysis of supragingival plaque samples collected by veterinarians from conscious and unconscious dogs demonstrated the assay had an accuracy of 77.7 to 80.9%, a sensitivity of 77.6 to 81.0%, and a specificity of 80.0%., Discussion: Use of this molecular screening tool in conscious dogs has the potential to improve early periodontal disease detection and support veterinary decision making, ultimately improving the oral health of dogs and consequently their quality of life., Competing Interests: CW, LC-M, RR, PB, TSM, TM, LH, PW, and AC are employees of Mars Petcare, a manufacturer of commercial petfood and provider of veterinary services. Mars Petcare has filed a number of patents relating to the compositional analysis of the canine oral microbiome as a diagnostic for canine periodontal disease. CH and MS-R received payment from Mars Petcare for consultation relating to this research. CH is employed by the company Colin Harvey LLC., (Copyright This work is authored by Wallis, Soltero-Rivera, Harvey, Reynolds, Carvell-Miller, Colyer, McKee, Millis, Bergman, Watson and Holcombe. © 2024 Mars Petcare UK and its affiliates for Wallis, Reynolds, Carvell-Miller, Colyer, Watson and Holcombe and © 2024 VCA Clinical Studies for McKee, Mills and Bergman.)

Craniofacial fibrous dysplasia (CFFD) is a benign, bony disease that may affect the skull base.1,2 Most cases are asymptomatic and observed; however, advanced disease can present with cranial neuropathy or craniofacial deformity requiring intervention.3-5 A 16-year-old adolescent girl with known CFFD involving the sphenoid and frontal bones with severe bilateral optic canal narrowing developed progressive right eye visual decline and frontal cosmetic deformity. Visual acuity worsened oculus dextrus (OD) to 20/30 with a new superior nasal scotoma and 20% loss in the retinal nerve fiber layer and remained oculus sinister (OS) 20/20. The patient was recommended a staged subfrontal craniotomy for right optic decompression and simultaneous correction cosmetic deformity followed by endonasal right optic decompression. On postoperative day one, visual acuity OD improved to 20/20; however, she developed OS visual decline to 20/800. Curiously, there were no episodes of intraoperative hypotension or additional iatrogenic compression. Use of methylprednisolone led to improvement OS 20/400. Given persistent visual decline, urgent second stage endonasal bilateral optic nerve decompression, rather than unilateral, was performed. Postoperatively, vision improved to OS 20/200. At one month, her vision improved to OD 20/15 and OS returned to 20/20 with a paracentral scotoma and 29% decline in left retinal nerve fiber layer with further improvement anticipated. This video describes a multidisciplinary, multistaged approach in treatment of optic nerve compression due to CFFD in addition to the management of unanticipated contralateral visual decline. The patient consented to the procedure and publication of her image. No Institutional Review Board/ethics committee approval was necessary for this case report., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: Endovascular treatment of complex vascular pathologies in the pediatric population is often performed by nonpediatric subspecialists with adaptation of equipment and techniques developed for adult patients. We aimed to report our center's experience with safety and outcomes of endovascular treatments for pediatric vascular pathologies., Methods: We performed a retrospective review of our endovascular database. All patients ≤18 years who underwent endovascular treatment between January 1, 2004 and December 1, 2022 were included., Results: During the study time frame, 118 cerebral angiograms were performed for interventional purposes in 55 patients. Of these patients, 8(14.5%) had intracranial aneurysms, 21(38.2%) had intracranial arteriovenous malformations, 6(10.9%) had tumors, 5(9.1%) had arterial occlusions (n = 3) or dissections (n = 2), 8(14.5%) had vein of Galen malformations, and 7(12.7%) had other cerebrovascular conditions. Of the total 118 procedures, access-site complications occurred in 2(1.7%), intraprocedural complications occurred in 3(2.5%), and transient neurological deficits were observed after 2(1.7%). Treatment-related mortality occurred in 1(1.8%) patient., Conclusions: Neurointervention in pediatric patients was safe and effective in our experience., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The U.S. Food and Drug Administration is considering a policy to reduce nicotine in cigarettes to non-addictive levels. Although current evidence supports the public-health benefits of a reduced-nicotine policy, almost half of people who smoke (∼ 40%) do not support the policy. This study estimates the factors most strongly associated with support or opposition toward the policy, including tobacco use status, perceived effects of a reduced nicotine policy, trust in the FDA, and psychological distress. The study aims to inform messaging campaigns and policy makers., Methods: Data were collected in 2021 with nationally representative samples of U.S. adults (n = 1763). After receiving information about the reduced nicotine policy, participants indicated their beliefs and support for or opposition to the policy, along with other individual difference characteristics. Univariate population parameters and multinomial logistic regression coefficients were estimated., Results: In adjusted models, people who formerly or never smoked were less likely to oppose the policy compared to those who currently smoke; people with higher psychological distress and those who believe the policy will promote switching to e-cigarettes were more likely to oppose the policy. In addition, people were more likely to support the policy if they believed it would make quitting easier or that the FDA is trustworthy., Conclusions: Educational campaigns about reduced nicotine policy should expect higher impact by targeting prevalent perceptions and those more strongly associated with policy sentiment. In anticipation of the policy rollout, there may be a critical window to shape public opinion., Competing Interests: Declaration of competing interest D.L.A. has received funds for work done for the World Health Organization Tobacco Free Initiative, as a consultant for Pfizer and McKing Consulting, Inc. (Atlanta, GA, USA), as an employee of Cherokee National Operational Systems, and as a Special Government Employee of the U.S. Food and Drug Administration., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Promoting minorities within medical specialties has been postulated to be crucial to patient care and recruitment of diverse candidates. This concept has been suspected but not formally studied in the minority of women faculty and trainees in neurosurgery. We aimed to quantitatively investigate the postulated correlation relative to female representation in neurosurgery., Methods: Data obtained from accredited neurosurgery residency programs were reviewed. Data describing the percentage of female residents and 6 demographic and 14 program-specific variables were collected. All program websites were reviewed to assess percentages of female faculty and visible commitment to diversity in applicants, evident through communicated policies, statements, or initiatives. Included programs were defined as "low" or "high" percentage of female residents or faculty relative to the grouped median value for both categories; groups were assessed for significant differences. Percentages of female faculty and residents and program-communicated diversity initiatives were investigated for significant correlation., Results: Female faculty and diversity data were available at 117 program sites; 81 programs reported female resident percentages. Analysis revealed a significant positive correlation between female faculty and female resident percentages. Programs with higher female resident percentages had higher levels of diversity in terms of race and ethnicity. No significant correlation was found between the percentage of female faculty or residents and a communicated diversity initiative., Conclusion: This study of current female representation in neurosurgery revealed a previously undocumented positive correlation between percentages of female faculty and female trainees. These data suggest a modifiable barrier to female entry into neurosurgical residency programs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Craniosynostosis is a developmental anomaly resulting from the premature fusion of cranial sutures, with an estimated incidence of 1 per 2000 to 1 per 2500 births.1 Surgical options for correction include open calvarial vault reconstruction, and more recently, endoscopic-assisted repairs that have been introduced to mitigate blood loss and hospital stay,2 although these remain understudied. In this operative video (Video), the authors present the case of an 11-month-old girl with right-sided coronal craniosynostosis that was treated with coronal cranial vault reconstruction with fronto-orbital advancement using computer-aided surgical simulation (KLS Martin Group), which has been studied previously with acceptable results when comparing the preoperative plan to the postoperative outcome.3 The patient was seen in follow-up at 1 month and 6 months and remained neurologically intact, continuing to meet all her developmental milestones appropriately. The patient's guardians consented to performance of the procedure and publication of the images. Institutional review board approval was deemed unnecessary. The participants and any identifiable individuals consented to publication of his/her images., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Craniofacial fibrous dysplasia (CFD) is a rare developmental disease of bone, which typically presents as a painless, expansile mass causing deformity of the craniofacial skeleton. In rare circumstances, compression of neurovascular structures may arise, causing symptoms such as pain, visual impairment, and hearing loss. Traditionally, CFD debulking has been performed with "freehand" techniques using preoperative imaging and anthropometric norms to determine the ideal amount of tissue removal. The advent of computer-assisted surgery, computer-aided design, and computer-aided manufacturing (CAD/CAM) has revolutionized the management of CFD. Surgeons can now fabricate patient-specific osteotomy/ostectomy guides, allowing for increased accuracy in bone removal and improved cosmetic outcomes. This series of 3 cases describe our institution's technique using patient-specific ostectomy "depth guides", which allow for maximum removal of fibro-osseous tissue while sparing deep and adjacent critical structures. These techniques can be widely applied to the craniofacial skeleton to assist in the surgical management of CFD., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objective: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19., Design: Retrospective multicentre cohort., Setting: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland., Population: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021)., Methods: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia., Main Outcome Measures: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission., Results: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic., Conclusions: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: USA is considering reducing nicotine in cigarettes to non-addictive levels, coupled with promoting alternative nicotine delivery products (eg, e-cigarettes). However, effective communication is needed to reduce misperceptions about very low nicotine cigarettes (VLNCs) being less harmful than regular cigarettes., Methods: In 2022-2023, we conducted a four-group randomised clinical trial with a national probability sample from an online panel (971 adults who smoked cigarettes exclusively, 472 adults who dual used cigarettes and e-cigarettes and 458 adults aged 18-29 who had never smoked). Participants were randomised (parallel assignment) to one message condition: (1) VLNCs as harmful but easier to quit than regular cigarettes (n=468), (2) those who are not ready to quit should consider switching to e-cigarettes as less harmful alternatives (n=484), (3) combined (VLNC and e-cigarette messages; n=476) or (4) control condition (ie, water ads), n=473. The primary outcome was perceived absolute harm of VLNCs., Results: Perceived harm of VLNCs was higher in the VLNC condition compared with the e-cigarette and control conditions, and higher in the combined condition compared with the e-cigarette condition (adjusted p<0.05). Among adults who dual used, intention to switch to e-cigarettes was higher in the VLNC condition than the e-cigarette, combined or control conditions (adjusted p<0.05)., Conclusions: VLNC messages reduced the misperception that VLNCs are less harmful than cigarettes, but adding messages about e-cigarettes did not enhance desired outcomes. These VLNC messages can be considered during the rollout of a reduced nicotine policy., Trial Registration: NCT05506046., Competing Interests: Competing interests: DLA has received funds for work done for the World Health Organization Tobacco Free Initiative, as a Special Government Employee of the U.S. Food and Drug Administration, as a consultant for Pfizer, as an employee of Cherokee National Operational Systems and as an independent contractor for MK Consulting., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To reduce smoking and the harms it causes, countries, including the USA, are considering policies to reduce nicotine in combustible tobacco to minimally addictive levels. Effective messages about very low nicotine cigarettes (VLNCs) and this policy are crucial in combating misperceptions threatening the policy's effectiveness., Data and Methods: A discrete choice experiment assessed messages about VLNCs. Participants were 590 adults who smoked exclusively, 379 adults who both smoked and used e-cigarettes, 443 adults who formerly smoked and 351 young adults who never smoked (total n=1763). Seven message attributes were varied systematically (source, harm, chemicals, nicotine, satisfaction, addictiveness and quitting efficacy). Outcomes were selection of messages that generated the most positive attitude towards reduced nicotine policy, the greatest perceived harmfulness of VLNCs, and most strongly motivated quitting and initiating behaviour for VLNCs., Results: Information about specific harms and chemicals of VLNCs had the largest effects on selection of messages as eliciting more negative attitudes towards VLNCs policy, increasing perceived VLNC harmfulness, increasing motivation to quit VLNCs and decreasing motivation to try VLNCs. Messages with information about quitting efficacy were selected as more motivating to quit among those who smoke, but also more motivating to try VLNCs among those who do not smoke., Conclusion: Harm and chemical information can be prioritised to ensure VLNCs are not misperceived as less harmful than regular cigarettes. Messages about increased quitting efficacy and reduced addictiveness associated with VLNCs may backfire if presented to those who do not smoke., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment., Method: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry., Results: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ 2 =0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively., Conclusions: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This study investigated sex differences in energy balance, body composition, and metabolic and endocrine markers during prolonged military training. Twenty-three trainees (14 women) completed 44-wk military training (three terms of 14 wk with 2-wk adventurous training). Dietary intake and total energy expenditure were measured over 10 days during each term by weighed food and doubly labeled water. Body composition was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at the end of each term. Circulating metabolic and endocrine markers were measured at baseline and at the end of terms 2 and 3 . Absolute energy intake and total energy expenditure were higher, and energy balance was lower, for men than women ( P ≤ 0.008). Absolute energy intake and balance were lower, and total energy expenditure was higher, during term 2 than terms 1 and 3 ( P < 0.001). Lean mass did not change with training ( P = 0.081). Fat mass and body fat increased from term 1 to terms 2 and 3 ( P ≤ 0.045). Leptin increased from baseline to terms 2 and 3 in women ( P ≤ 0.002) but not in men ( P ≥ 0.251). Testosterone and free androgen index increased from baseline to term 3 ( P ≤ 0.018). Free thyroxine (T4) decreased and thyroid-stimulating hormone (TSH) increased from baseline to term 2 and term 3 ( P ≤ 0.031). Cortisol decreased from baseline to term 3 ( P = 0.030). IGF-I and total triiodothyronine (T3) did not change with training ( P ≥ 0.148). Men experienced greater energy deficits than women during military training due to higher total energy expenditure. NEW & NOTEWORTHY Energy deficits are common in military training and can result in endocrine and metabolic disturbances. This study provides first investigation of sex differences in energy balance, body composition, and endocrine and metabolic markers in response to prolonged and arduous military training. Men experienced greater energy deficits than women due to higher energy expenditure, which was not compensated for by increased energy intake. These energy deficits were not associated with decreases in fat or lean mass or metabolic or endocrine function.

Objective: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies., Design/patients: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study)., Measurements: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD)., Results: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores., Conclusions: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine., Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model., Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature ( p  > 0.063). There was no significant effect of treatment on heart rate ( p  = 0.364). There was a significant effect of time ( p  = 0.003) on heart rate with overall heart rates being less than baseline at 64 h., Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Reed, Berghaus, Reynolds, Holmes, Krikorian, Sakai, Ishikawa and Knych.)

Background and Objective: Computer-aided surgical simulation (CASS) can be used to virtually plan ideal outcomes of craniosynostosis surgery. Our purpose was to create a workflow analyzing the accuracy of surgical outcomes relative to virtually planned fronto-orbital advancement (FOA)., Methods: Patients who underwent FOA using CASS between October 1, 2017, and February 28, 2022, at our center and had postoperative computed tomography within 6 months of surgery were included. Virtual 3-dimensional (3D) models were created and coregistered using each patient's preoperative and postoperative computed tomography data. Three points on each bony segment were used to define the object in 3D space. Each planned bony segment was manipulated to match the actual postoperative outcome. The change in position of the 3D object was measured in translational (X, Y, Z) and rotational (roll, pitch, yaw) aspects to represent differences between planned and actual postoperative positions. The difference in the translational position of several bony landmarks was also recorded. Wilcoxon signed-rank tests were performed to measure significance of these differences from the ideal value of 0, which would indicate no difference between preoperative plan and postoperative outcome., Results: Data for 63 bony segments were analyzed from 8 patients who met the inclusion criteria. Median differences between planned and actual outcomes of the segment groups ranged from -0.3 to -1.3 mm in the X plane; 1.4 to 5.6 mm in the Y plane; 0.9 to 2.7 mm in the Z plane; -1.2° to -4.5° in pitch; -0.1° to 1.0° in roll; and -2.8° to 1.0° in yaw. No significant difference from 0 was found in 21 of 24 segment region/side combinations. Translational differences of bony landmarks ranged from -2.7 to 3.6 mm., Conclusion: A high degree of accuracy was observed relative to the CASS plan. Virtual analysis of surgical accuracy in FOA using CASS was feasible., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background and Objectives: Social determinants of health (SDOH) are nonmedical factors that affect health outcomes. Limited investigation has been completed on the potential association of these factors to adverse outcomes in pediatric populations. In this study, the authors aimed to analyze the effects of SDOH disparities and their relationship with outcomes after brain tumor resection or biopsy in children., Methods: The authors retrospectively reviewed the records of their center's pediatric patients with brain tumor. Black race, public insurance, median household income, and distance to hospital were the investigated SDOH factors. Univariate analysis was completed between number of SDOH factors and patient demographics. Multivariate linear regression models were created to identify coassociated determinants and outcomes., Results: A total of 272 patients were identified and included in the final analysis. Among these patients, 81 (29.8%) had no SDOH disparities, 103 (37.9%) had 1, 71 (26.1%) had 2, and 17 (6.2%) had 3. An increased number of SDOH disparities was associated with increased percentage of missed appointments ( P = .002) and emergency room visits ( P = .004). Univariate analysis demonstrated increased missed appointments ( P = .01), number of postoperative imaging ( P = .005), and number of emergency room visits ( P = .003). In multivariate analysis, decreased median household income was independently associated with increased length of hospital stay ( P = .02)., Conclusion: The SDOH disparities are prevalent and impactful in this vulnerable population. This study demonstrates the need for a shift in research focus toward identifying the full extent of the impact of these factors on postoperative outcomes in pediatric patients with brain tumor., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Purpose: Although social determinants of health (SDOH) have been associated with adverse surgical outcomes, cumulative effects of multiple SDOH have never been studied. The area deprivation index (ADI) assesses cumulative impact of SDOH factors on outcomes. We analyzed the relationship between ADI percentile and postoperative outcomes in pediatric patients diagnosed with brain tumors., Methods: A retrospective, observational study was conducted on our consecutive series of pediatric brain tumor patients presenting between January 1, 1999, and May 31, 2022. Demographics and outcomes were collected, identifying SDOH factors influencing outcomes found in the literature. ADI percentiles were identified based on patient addresses, and patients were stratified into more (ADI 0-72%) and less (ADI 73-100%) disadvantaged cohorts. Univariate and multivariate logistic regression analyses were completed for demographics and outcomes., Results: A total of 272 patients were included. Demographics occurring frequently in the more disadvantaged group were Black race (13.1% vs. 2.8%; P = .003), public insurance (51.5% vs. 27.5%; P < .001), lower median household income ($64,689 ± $19,254 vs. $46,976 ± $13,751; P < .001), and higher WHO grade lesions (15[11.5%] grade III and 8[6.2%] grade IV vs. 8[5.6%] grade III and 5[3.5%] grade IV; P = .11). The more disadvantaged group required adjunctive chemotherapy (25.4% vs. 12.05%; P = .007) or radiation therapy (23.9% vs. 12.7%; P = .03) more frequently and had significantly greater odds of needing adjunctive chemotherapy (odds ratio [OR], 1.11; confidence interval [CI], 1.01-1.22; P = .03) in a multivariate model, which also identified higher WHO tumor grades at presentation (OR, 1.20; CI, 1.14-1.27; P < .001)., Conclusion: These findings are promising for use of ADI to represent potential SDOH disadvantages that pediatric patients may face throughout treatment. Future studies should pursue large multicenter collaborations to validate these findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The U.S. Food and Drug Administration (FDA) has proposed rulemaking to reduce the nicotine content in cigarettes and other combusted tobacco products to non-addictive levels. This qualitative study documents reactions to messages communicating this policy among people who use little cigars and cigarillos (LCCs)., Aims and Methods: We conducted eight focus groups with participants from four populations with the highest prevalence of cigar use (African American males and females, white males and females). Participants described their reactions to eight messages about the policy: Three messages about the equal risk of LCCs with regular and low nicotine levels; three quit efficacy messages about low nicotine LCCs being easier to quit; one "compensation" message to correct misperceptions about the policy causing people to smoke more to get desired nicotine; and one message about using alternative nicotine sources (eg, e-cigarettes)., Results: Participants perceived risk messages as the most motivating to quit, whereas efficacy messages made some participants feel that the policy would cause former users of LCCs to relapse. Many participants expressed favorable responses to the compensation message. The message about using alternative nicotine sources sparked intense responses, with many participants expressing outrage and mistrust of the message. Participants' beliefs that they were not addicted to LCCs dampened their perceptions of the effectiveness of the policy., Conclusions: Perceptions of the addictiveness and relative harms of LCCS influenced responses to policy messages. The FDA should consider using different messages to communicate with people who use LCCs because they perceive LCCs as different from cigarettes., Implications: This is the first study to document affective and cognitive responses to the FDA's reduced nicotine policy among people who use LCCs. The false belief that cigar products are less harmful than cigarettes may be influencing people's lack of support for the reduced nicotine policy and difficulty in understanding its potential positive impact. To maximize the public health benefit of the reduced nicotine policy, the FDA should include LCC products in the policy; however, it is crucial that they use educational messaging to clarify misperceptions regarding nicotine and harm as it applies to LCCs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Low birth weight (BW) is consistently correlated with increased parental risk of subsequent cardiovascular disease, but the links with offspring placental weight (PW) are mostly unexplored. We have investigated the associations between parental coronary heart disease (CHD) and offspring BW and PW using the Walker cohort, a collection of 48,000 birth records from Dundee, Scotland, from the 1950s and 1960s. We linked the medical history of 13,866 mothers and 8,092 fathers to their offspring's records and performed Cox survival analyses modelling maternal and paternal CHD risk by their offspring's BW, PW, and the ratio between both measurements. We identified negative associations between offspring BW and both maternal (hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.88-0.95) and paternal (HR: 0.96, 95% CI: 0.93-1.00) CHD risk, the stronger maternal correlation being consistent with previous reports. Offspring PW to BW ratio was positively associated with maternal CHD risk (HR: 1.14, 95% CI: 1.08-1.21), but the associations with paternal CHD were not significant. These analyses provide additional evidence for intergenerational associations between early growth and parental disease, identifying directionally opposed correlations of maternal CHD with offspring BW and PW, and highlight the importance of the placenta as a determinant of early development and adult disease.

Introduction: Recent high-profile calls have emphasized that women's experiences should be considered in maternity care provisioning. We explored women's experiences of using closed-loop during type 1 diabetes (T1D) pregnancy to inform decision-making about antenatal rollout and guidance and support given to future users. Methods: We interviewed 23 closed-loop participants in the Automated insulin Delivery Among Pregnant women with T1D (AiDAPT) trial after randomization to closed-loop and ∼20 weeks later. Data were analyzed thematically. Results: Women described how closed-loop lessened the physical and mental demands of diabetes management, enabling them to feel more normal and sleep better. By virtue of spending increased time-in-range, women also worried less about risks to their baby and being judged negatively by health care professionals. Most noted that intensive input and support during early pregnancy had been crucial to adjusting to, and developing confidence in, the technology. Women emphasized that attaining pregnancy glucose targets still required ongoing effort from themselves and the health care team. Women described needing education to help them determine when, and how, to intervene and when to allow the closed-loop to operate without interference. All women reported more enjoyable pregnancy experiences as a result of using closed-loop; some also noted being able to remain longer in paid employment. Conclusions: Study findings endorse closed-loop use in T1D pregnancy by highlighting how the technology can facilitate positive pregnancy experiences. To realize fully the benefits of closed-loop, pregnant women would benefit from initial intensive oversight and support together with closed-loop specific education and training. Clinical Trial Registration number: NCT04938557.

Objective: Medulloblastoma is the most common malignant intracranial tumor affecting the pediatric population. Despite advancements in multimodal treatment over the past 2 decades yielding a 5-year survival rate > 75%, children who survive often have substantial neurological and cognitive sequelae. The authors aimed to identify risk factors and develop a clinically friendly online calculator for prognostic estimation in pediatric patients with medulloblastoma., Methods: Pediatric patients with a histopathologically confirmed medulloblastoma were extracted from the Surveillance, Epidemiology, and End Results database (2000-2018) and split into training and validation cohorts in an 80:20 ratio. The Cox proportional hazards model was used to identify the univariate and multivariate survival predictors. Subsequently, a calculator with those factors was developed to predict 2-, 5-, and 10-year overall survival as well as median survival months for pediatric patients with medulloblastoma. The performance of the calculator was determined by discrimination and calibration., Results: One thousand seven hundred fifty-nine pediatric patients with medulloblastoma met the prespecified inclusion criteria. Age, sex, race, ethnicity, median household income, county attribute, laterality, anatomical location, tumor grade, tumor size, surgery status, radiotherapy, and chemotherapy were variables included in the calculator (https://spine.shinyapps.io/Peds&#95;medullo/). The concordance index was 0.769 in the training cohort and 0.755 in the validation cohort, denoting clinically useful predictive accuracy. Good agreement between the predicted and observed outcomes was demonstrated by the calibration plots., Conclusions: An easy-to-use prognostic calculator for a large cohort of pediatric patients with medulloblastoma was established. Future efforts should focus on improving granularity of population-based registries and externally validating the proposed calculator.

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth., (© 2023. The Author(s).)

Background: Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear., Methods: In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events., Results: A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy)., Conclusions: Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.)., (Copyright © 2023 Massachusetts Medical Society.)

Gestational diabetes and the maternal mental disorders of anxiety and depression have been implicated in adverse offspring neuro-behavioural outcomes but these exposures have only been studied in isolation. 1051 children whose mothers were diagnosed with gestational diabetes in UK's Born in Bradford cohort had linkage to maternal primary care records, providing diagnostic and treatment codes for depression and anxiety. Education record linkage provided results of the Early Years Foundation Stage Profile from the first year of school, aged five. Risk of not attaining a 'Good level of development' was analysed using multivariable Poisson regression within a generalised estimating equation framework. Multiple imputation was implemented for missing data. There was limited evidence of increased risk of failure to attain a 'good level of development' in those additionally exposed to maternal mental disorders (adjusted RR 1.21; 95% CI 0.94, 1.55). However, there was more evidence in children of Pakistani maternal ethnicity (adjusted RR 1.36; 95% CI 1.04, 1.77) than White British; this may have been driven by English not being the primary language spoken in the home. Therefore there may be groups with GDM in whom it is particularly important to optimise both maternal physical and mental health to improve child outcomes., (© 2023. Springer Nature Limited.)

In this review, we summarise the current epidemiological and experimental evidence on the association of ambient (outdoor) air pollution exposure and maternal cardiovascular health during pregnancy. This topic is of utmost clinical and public health importance as pregnant women represent a potentially susceptible group due to the delicate balance of the feto-placental circulation, rapid fetal development and tremendous physiological adaptations to the maternal cardiorespiratory system during pregnancy.Several meta-analyses including up to 4 245 170 participants provide robust evidence that air pollutants, including particulate matter, nitrogen oxides and others, have adverse effects on the development of hypertensive disorders of pregnancy, gestational diabetes mellitus and cardiovascular events during labour. Potential underlying biological mechanisms include oxidative stress with subsequent endothelial dysfunction and vascular inflammation, β-cell dysfunction and epigenetic changes. Endothelial dysfunction can lead to hypertension by impairing vasodilatation and promoting vasoconstriction. Air pollution and the consequent oxidative stress can additionally accelerate β-cell dysfunction, which in turn triggers insulin resistance leading to gestational diabetes mellitus. Epigenetic changes in placental and mitochondrial DNA following air pollution exposures can lead to altered gene expression and contribute to placental dysfunction and induction of hypertensive disorders of pregnancy.The maternal and fetal consequences of such cardiovascular and cardiometabolic disease during pregnancy can be serious and long lasting, including preterm birth, increased risk of type 2 diabetes mellitus or cardiovascular disease later in life. Acceleration of efforts to reduce air pollution is therefore urgently needed to realise the full health benefits for pregnant mothers and their children., Competing Interests: Competing interests: DEN is on the Editorial Board for Heart., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus., Methods: We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions., Results: There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis., Conclusions: Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies., (© 2023. Springer Nature Limited.)

Aims: To investigate whether manganese-enhanced magnetic resonance imaging can assess functional pancreatic beta-cell mass in people with type 1 diabetes mellitus., Methods: In a prospective case-control study, 20 people with type 1 diabetes mellitus (10 with low (≥50 pmol/L) and 10 with very low (<50 pmol/L) C-peptide concentrations) and 15 healthy volunteers underwent manganese-enhanced magnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescan reproducibility was performed in 10 participants., Results: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/min in healthy volunteers (median 32 [interquartile range 23-36] years, 6 women), falling to 23 ± 4 and 13 ± 5 mL/100 g of tissue/min (p ≤ 0.002 for both) in people with type1 diabetes mellitus (52 [44-61] years, 6 women) and low or very low plasma C-peptide concentrations respectively. Pancreatic manganese uptake correlated strongly with plasma C-peptide concentrations in people with type1 diabetes mellitus (r = 0.73, p < 0.001) but not in healthy volunteers (r = -0.054, p = 0.880). There were no statistically significant correlations between manganese uptake and age, body-mass index, or glycated haemoglobin. There was strong intra-observer (mean difference: 0.31 (limits of agreement -1.42 to 2.05) mL/100 g of tissue/min; intra-class correlation, ICC = 0.99), inter-observer (-1.23 (-5.74 to 3.27) mL/100 g of tissue/min; ICC = 0.85) and scan-rescan (-0.72 (-2.9 to 1.6) mL/100 g of tissue/min; ICC = 0.96) agreement for pancreatic manganese uptake., Conclusions: Manganese-enhanced magnetic resonance imaging provides a potential reproducible non-invasive measure of functional beta-cell mass in people with type 1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoring disease progression and assessing novel immunomodulatory interventions., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Equine pain scoring may be affected by the residual effect of anesthetic drugs., Objectives: To compare pain scores in the hours immediately following anesthetic recovery to baseline pre-anesthetic scores in equine patients undergoing surgical and non-surgical procedures., Study Design: Clinical observational study., Methods: Fifty adult horses undergoing anesthesia for surgical or non-surgical procedures were enrolled. Horses underwent pain scoring using the Composite Pain Score (CPS) and Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) prior to anesthesia (T0) and following anesthetic recovery to standing, every hour for 5 h (T1-T5). Data were analyzed using a generalized linear mixed effects model. A post-hoc Dunnett's test for multiple comparisons was performed for variables where an effect was detected., Results: Mean (95% confidence interval) CPS scores for T0-T5 were 1.6 (1.2-2.0), 6.8 (6.0-7.6), 5.1 (4.3-5.9), 4.3 (3.4-5.2), 3.7 (2.8-4.6), and 2.8 (2.0-3.6) and EQUUS-FAP scores were 0.6 (0.3-0.9), 3.0 (2.5-3.5), 1.9 (1.6-2.2), 1.1 (0.8-1.4), 0.6 (0.4-0.8), and 0.7 (0.4-1.0), respectively. For the CPS, scores greater than 5, and for the EQUUS-FAP scores greater than 3, are consistent with minor pain. There was no effect of type of procedure (surgical vs non-surgical) on CPS or EQUUS-FAP scores. There was an effect of time with CPS scores significantly greater than baseline at T1-T5 and EQUUS-FAP scores significantly greater than baseline at T1 and T2., Main Limitations: Discomfort caused by hoisting was not quantified and it was difficult to ascertain if this affected the results., Conclusions: Post-anesthetic pain scores may be influenced by the residual effect of anesthetic agents for as long as 5 h and 2 h for the CPS and EQUUS-FAP, respectively., 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., (© 2023 Reed, Krikorian, Reynolds, Holmes, Branning, Lemons, Barletta, Quandt, Burns, Dantino and Sakai.)

Objective: This study provided a first empirical test of the Reverse Dynamic Theory of Reasoned Action (RDTRA) developed by Boster et al., Design: In a longitudinal experiment, 169 participants were exposed to a WHO handwashing-guidelines behavioural induction, followed by an immediate posttest and a follow-up one week later., Main Outcome Measures: The study measured attitudes and norms about WHO handwashing guidelines, as well as self-reported handwashing behaviour., Results: The experimental induction produced variance in self-reported handwashing behaviour, allowing a test of the RDTRA using path analysis and structural equation modelling (SEM). Results were consistent with the RDTRA, with a positive effect of behaviour on both the attitude and norm coupled with excellent model fit. Results were inconsistent with behaviour as an outcome of attitudes and norms in this context., Conclusion: For health behaviours, such as the WHO handwashing technique, initial behavioural adoption may promote subsequent shaping of attitudes and perceived norms. Boundary conditions for this effect may include the degree of spontaneity and consent involved in behaviour adoption.

Background: The role of positive maternal mental health during pregnancy in child mental health remains largely unknown. We investigated whether positive maternal mental health during pregnancy is associated with lower hazards of mental and behavioral disorders in children and mitigates the adverse effects of negative maternal mental health., Methods: Among 3,378 mother-child dyads of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study, mothers reported their positive mental health biweekly throughout pregnancy with the Positive and Negative Affect Schedule, the Spielberger State Anxiety Inventory Curiosity scale, and a visual analogue scale for social support, and negative mental health with the Center for Epidemiologic Studies Depression Scale. We extracted data on their mental and behavioral disorder diagnoses from a nationwide medical register. This register provided data on their children's mental and behavioral disorder diagnoses as well, from birth until 8.4-12.8 (Median = 10.2, Interquartile Range 9.7-10.8) years of age., Results: A positive maternal mental health composite score during pregnancy was associated with a lower hazard of any mental and behavioral disorder among all children [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI) 0.71 - 0.87] and among children of mothers experiencing clinically relevant depressive symptoms during pregnancy [HR = 0.80, 95%CI 0.64 - 1.00] and/or mental and behavioral disorders before or during pregnancy [HR = 0.69, 95%CI 0.55-0.86]. These associations were independent of covariates., Conclusions: Children whose mothers had more positive mental health during pregnancy were less likely to develop mental and behavioral disorders. Protective effects were seen also among children of mothers facing mental health adversities before or during pregnancy., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Interest is growing in how closed-loop systems can support attainment of within-target glucose levels amongst pregnant women with type 1 diabetes. We explored healthcare professionals' views about how, and why, pregnant women benefitted from using the CamAPS FX system during the AiDAPT trial., Methods: We interviewed 19 healthcare professionals who supported women using closed-loop during the trial. Our analysis focused on identifying descriptive and analytical themes relevant to clinical practice., Results: Healthcare professionals highlighted clinical and quality-of-life benefits to using closed-loop in pregnancy; albeit, they attributed some of these to the continuous glucose monitoring component. They emphasised that the closed-loop was not a panacea and that, to gain maximum benefit, an effective collaboration between themselves, the woman and the closed-loop was needed. Optimal performance of the technology, as they further noted, also required women to interact with the system sufficiently, but not excessively; a requirement that they felt some women had found challenging. Even where healthcare professionals felt that this balance was not achieved, they suggested that women had still benefitted from using the system. Healthcare professionals reported difficulties predicting how specific women would engage with the technology. In light of their trial experiences, healthcare professionals favoured an inclusive approach to closed-loop rollout in routine clinical care., Conclusions: Healthcare professionals recommended that closed-loop systems be offered to all pregnant women with type 1 diabetes in the future. Presenting closed-loop systems to pregnant women and healthcare teams as one pillar of a three-party collaboration may help promote optimal use., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Introduction: Whole exome sequencing (WES) has increasingly become integrated into prenatal care and genetic testing pathways. Current studies of prenatal WES have focused on diagnostic yield. The possibility of obtaining a variant of uncertain significance and lack of provider expertise are frequently described as common barriers to clinical integration of prenatal WES. We describe the implementation and workflow for a multidisciplinary approach to effectively integrate prenatal WES into maternal-fetal care to overcome these barriers., Methods: A multidisciplinary team reviews and approves potential cases for WES. This team reviews WES results, reclassifying variants as appropriate and provides recommendations for postnatal care. A detailed description of this workflow is provided, and a case example is included to demonstrate effectiveness of this approach. Our team has approved 62 cases for WES with 45 patients ultimately pursuing WES. We have achieved a diagnostic yield of 40% and the multidisciplinary team has played a role in variant interpretation in 50% of the reported variants of uncertain significance., Conclusions: This approach facilitates communication between prenatal and postnatal care teams and provides accurate interpretation and recommendations for identified fetal variants. This model can be replicated to ensure appropriate patient care and effective integration of novel genomic technologies into prenatal settings., (© 2023 John Wiley & Sons Ltd.)

Background: Earlier pubertal timing is associated with higher rates of depressive disorders in adolescence. Neuroimaging studies report brain structural associations with both pubertal timing and depression. However, whether brain structure mediates the relationship between pubertal timing and depression remains unclear., Methods: The current registered report examined associations between pubertal timing (indexed via perceived pubertal development), brain structure (cortical and subcortical metrics, and white matter microstructure) and depressive symptoms in a large sample (N = ∼5000) of adolescents (aged 9-13 years) from the Adolescent Brain Cognitive Development (ABCD) Study. We used three waves of follow-up data when the youth were aged 10-11 years, 11-12 years, and 12-13 years, respectively. We used generalised linear-mixed models (H1) and structural equation modelling (H2 & H3) to test our hypotheses., Hypotheses: We hypothesised that earlier pubertal timing at Year 1 would be associated with increased depressive symptoms at Year 3 (H1), and that this relationship would be mediated by global (H2a-b) and regional (H3a-g) brain structural measures at Year 2. Global measures included reduced cortical volume, thickness, surface area and sulcal depth. Regional measures included reduced cortical thickness and volume in temporal and fronto-parietal areas, increased cortical volume in the ventral diencephalon, increased sulcal depth in the pars orbitalis, and reduced fractional anisotropy in the cortico-striatal tract and corpus callosum. These regions of interest were informed by our pilot analyses using baseline ABCD data when the youth were aged 9-10 years., Results: Earlier pubertal timing was associated with increased depressive symptoms two years later. The magnitude of effect was stronger in female youth and the association remained significant when controlling for parental depression, family income, and BMI in females but not in male youth. Our hypothesised brain structural measures did not however mediate the association between earlier pubertal timing and later depressive symptoms., Conclusion: The present results demonstrate that youth, particularly females, who begin puberty ahead of their peers are at an increased risk for adolescent-onset depression. Future work should explore additional biological and socio-environmental factors that may affect this association so that we can identify targets for intervention to help these at-risk youth., (Copyright © 2023. Published by Elsevier Ltd.)

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed ( n  = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving ( n  = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.

While the US Food and Drug Administration (FDA)'s proposal to reduce the nicotine content in cigarettes is gaining traction, it is still undetermined whether the policy will also include other combustible tobacco products, such as little cigars and cigarillos (LCCs), and how such a policy should be communicated given the patterns of use and perceptions around LCCs. This study examined perceptions of nicotine and addiction related to LCC use and involved data collection from eight semi-structured virtual focus groups conducted in Summer 2021 in the US. Participants were adults who reported past-30-day use of LCCs, consisting of African American males ( n = 9), African American females ( n = 9), white males ( n = 14), and white females ( n = 11). Participants discussed their perceptions of nicotine and addiction in general and in relation to LCC use. Inductive thematic analysis of transcripts was conducted. Differences across race and sex groups were examined. Participants did not consider nicotine to be a characterizing feature of LCCs; rather, they generally associated nicotine with cigarettes. Participants' views of nicotine and addiction related to LCCs were discussed along four dimensions: context of use, frequency of use, the presence of cravings, and whether a product is modified (e.g., by adding marijuana). Social and infrequent use, a lack of cravings, and the use of LCCs for marijuana were considered indicative of a lack of addiction and reasons not to be concerned about nicotine in LCCs. Because perceptions of nicotine and addiction related to LCCs differ from those of cigarettes, communications about a reduced nicotine policy that includes LCCs should consider these differences to ensure the policy is understood by people who currently use LCCs and to prevent people who use cigarettes from switching to LCCs.

Background: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure., Methods: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records., Results and Discussion: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Frier 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.)

Study Design: The investigators designed and implemented a 20-year cross-sectional study using the National Electronic Injury Surveillance System database., Objective: The purpose of this study is to estimate and compare hospital admission (danger) rates between rugby and football of those who presented to the emergency department with head and neck injuries after playing these sports., Methods: The primary predictor variable was sport played. The primary outcome variable was danger, measured by hospital admission rates., Results: Over the past 20 years, there has been a trend of decreasing incidence of injuries presenting to the emergency department in both sports. There was no difference in the rate of hospital admission when comparing football and rugby (OR, 1.2; P = .1). Male gender was associated with an increased risk of admission. Other variables associated with hospital admission included white racial group, injury taking place in the fall, being either young (15-24 years old) or senior (65 years of age and over), and being injured at school or at a sport/recreational facility., Conclusions: There is no difference in danger as measured by admission rates between American football and rugby. There exists, however, several variables that are associated with admission when sustaining injury to the head and neck, when playing these two sports., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Responses to hormones that act through nuclear receptors are controlled by modulating hormone concentrations not only in the circulation but also within target tissues. The role of enzymes that amplify or reduce local hormone concentrations is well established for glucocorticoid and other lipophilic hormones; moreover, transmembrane transporters have proven critical in determining tissue responses to thyroid hormones. However, there has been less consideration of the role of transmembrane transport for steroid hormones. ATP-binding cassette (ABC) proteins were first shown to influence the accumulation of glucocorticoids in cells almost three decades ago, but observations over the past 10 years suggest that differential transport propensities of both exogenous and endogenous glucocorticoids by ABCB1 and ABCC1 transporters provide a mechanism whereby different tissues are preferentially sensitive to different steroids. This Review summarizes this evidence and the new insights provided for the physiology and pharmacology of glucocorticoid action, including new approaches to glucocorticoid replacement., (© 2022. Springer Nature Limited.)

Introduction: Despite recommendation that all women receive an ultrasound in pregnancy prior to 24 weeks', this remains unavailable to many women in low-income countries where trained practitioners are scarce. Although many programmes have demonstrated efficacy, few have achieved longterm sustainability, with a lack of information about how best to implement such programmes. This mixed-methods study aimed to evaluate the implementation of a novel education package to teach ultrasound-naive midwives in Malawi basic obstetric ultrasound, assessing its impact in the context of the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework., Methods: The study ran across six sites in Malawi between October 2020 and June 2021, encompassing three phases; pre-implementation, implementation and post-implementation. Twenty nine midwives underwent a bespoke education package with matched pre and post course surveys assessed their knowledge, attitudes and confidence and "hands on" assessments evaluating practical skills. Training evaluation forms and in-depth interviews explored their satisfaction with the package, with repeat assessment and remote image review evaluating maintenance of skills., Results: 28/29 midwives completed the training, with significant increases in knowledge, confidence and practical skills. Adherence to the education package varied, however many changes to the proposed methodology were adaptive and appeared to facilitate the efficacy of the programme. Unfortunately, despite reporting approval regarding the training itself, satisfaction regarding supervision and follow up was mixed, reflecting the difficulties encountered with providing ongoing in-person and remote support., Conclusion: This programme was successful in improving trainees' knowledge, confidence and skill in performing basic obstetric ultrasound, largely on account of an adaptive approach to implementation. The maintenance of ongoing support was challenging, reflected by trainee dissatisfaction. By evaluating the success of this education package based on its implementation and not just its efficacy, we have generated new insights into the barriers to sustainable upscale, specifically those surrounding maintenance., 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 Viner, Malata, Mtende, Membe-Gadama, Masamba, Makwakwa, Bamuya, Lissauer, Stock, Norman, Reynolds, Magowan, Freyne, Gadama, Cunningham-Burley, Nyondo-Mipando and Chipeta.)

Background: To better understand the various influences of COVID-19 on tobacco use, we examined three different tobacco user groups using qualitative methods., Methods: Ten online focus groups with 61 adults from the Atlanta, GA area were held in October-November 2020: four with exclusive smokers (n = 16), three with Electronic Nicotine Delivery System (ENDS) users (dual and exclusive, n = 22), and three with transitioning (recently quit or currently quitting) smokers and/or ENDS users (n = 23)., Results: Exclusive smokers reported smoking more frequently, driven by COVID-19-related stress, time at home, and boredom. They were not motivated to quit during the pandemic, and some considered smoking to be protective against COVID-19. ENDS users reported vaping less, with dual users often increasing their smoking; many were concerned about health effects of smoking and ENDS use during the pandemic. Transitioning smokers/ENDS users worried about their health and wanted to quit, but many found the stress of COVID-19 unbearable without tobacco use., Conclusions: There were some similarities among the groups, but also pronounced differences. Educational campaigns should capitalize on the teachable moment of COVID-19 to increase perceived risk of smoking. Smokers need access to more adaptive ways to deal with stress (such as mindfulness training) in lieu of smoking and systems-level approaches should address structural determinants of health that cause high levels of stress. The proposed policy to lower nicotine in combusted tobacco products might help smokers choose other means of coping instead of cigarettes by reducing the stress-relieving properties of smoking particularly salient during the pandemic., Implications: Smokers believe that cigarettes help them deal with the stresses and challenges of the COVID-19 pandemic. This needs to be counteracted by educational campaigns to increase perceived harm of smoking, alternative stress-relief strategies, and mandated changes to the combusted tobacco products to make them less appealing., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)