bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can frailty in conjunction with FRAX identify additional women at risk of fracture - a longitudinal cohort study of community dwelling older women
Authors: Bartosch Patrik , Malmgren Linnea 
Published: December 2022

Abstract
Background
Fracture risk assessment is still far from perfect within the geriatric population. The overall aim of this study is to better identify older women at risk for fractures, using a quantitative measure of frailty in conjunction with the web-based Fracture Risk Assessment Tool (FRAX®).

Methods
This study was performed in the Osteoporosis Risk Assessment (OPRA) cohort of n = 1023, 75-year-old women followed for 10-years. A frailty index (FI) of ‘deficits in health’ was created, and FRAX 10-year probability for major osteoporotic and hip fractures was calculated and bone mineral density measured. Incident fractures were continuously registered for 10-years. Receiver Operating Characteristic (ROC) curves were used to compare FI, FRAX and the combination FI + FRAX as instruments for risk prediction. Discriminative ability was estimated by comparing Area Under the Curve (AUC). In addition, using guidelines from the Swedish Osteoporosis Foundation, a category of low risk women who would not have been recommended for pharmacological treatment (non-treatment group) was identified, categorized by frailty status and for relative risk analysis, hazard ratios (HR) and 95% confidence intervals were calculated using Cox proportional hazard regressions.

Results
For hip fracture, FRAX and frailty performed almost equally (HIP AUC 10y: 0.566 vs. 0.567, p = 0.015 and p = 0.013). Next, FI was used in conjunction with FRAX; proving marginally better than either score alone (AUC 10y: 0.584, p = 0.002). Comparable results were observed for osteoporotic fracture.
In the non-treatment group (564 women), being frail was associated with higher 10y hip fracture risk (HR 2.01 (1.13–3.57)), although failing to reach statistical significance for osteoporotic fracture (HR 1.40 (0.97–2.01).
The utility of measuring frailty was also demonstrated when using T-score as an index of bone density to define fracture risk. Among n = 678 non-osteoporotic women, frailty added to the 10-year fracture risk (Hip; HR 2.22 (1.35–3.71); Osteoporotic fracture; HR 1.57 (1.15–2.14)).

Conclusions
While the addition of frailty to FRAX marginally improved fracture prediction, applying a frailty measurement to a group of ‘low risk’ women, identified a set of individuals with high actual hip fracture risk that would not be prioritized for pharmacological treatment. Further cost-benefit analysis studies are needed to formally test potential benefit.
PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study
Authors: Willacker L. , Raiser T. M. , Bassi M. , Bender A. , Comanducci A. , Rosanova M. , Sobel N. , Arzi A. , Belloli L. , Casarotto S. , Colombo M. , Derchi C. C. , Fló Rama E. , Grill E. , Hohl M. , Kuehlmeyer K. , Manasova D. , Rosenfelder M. J. , Valota C. , Sitt J. D. 
Published: December 2022

Abstract
Background
Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project “PerBrain” is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients.

Methods
In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients’ clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients’ informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase.

Discussion
Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients’ neurological status and their caregivers’ mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members.

Trial registration
ClinicalTrials.gov, NCT04798456. Registered 15 March 2021 – Retrospectively registered.
Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report
Authors: Vithayathil Joseph , Freeman Colbey , Jacobwitz Marin , Schwartz Erin Simon , Agarwal Sonika 
Published: December 2022

Abstract
Background
Electroconvulsive therapy is used to treat depression and schizophrenia with infrequent use in pediatric patients. We report a case of an adolescent with autism spectrum disorder and acute catatonia that presented with status epilepticus (SE) and prolonged neurologic deficits with unilateral left cerebral edema on imaging following unilateral electroconvulsive therapy (ECT) on the right side, subsequently found to have a CACNA1a pathogenic variant. This case highlights a potential adverse effect of ECT in patients with CACNA1a related disorders.

Case
The patient received unilateral ECT to the right side and subsequently had an episode of SE with right-sided hemiplegia for 72 h prior to regaining some function with persistent mild right-hand weakness that persisted for at least 1–2 weeks. A brain MRI 2 days after ECT was unremarkable, but a repeat MRI on day four of admission showed left hemisphere cortical diffusion restriction, increased perfusion and T2 prolongation suggestive of cortical edema. They had whole exome genetic testing sent after discharge that showed a known pathogenic CACNA1a variant (p.I1709T). CACNA1a encodes the P/Q type calcium channels and deleterious variants in this gene result in a channelopathy associated with a spectrum of neurodevelopmental disorders that include autism spectrum disorder, hemiplegic migraine with unilateral cerebral edema, epileptic encephalopathies, or episodic ataxia syndromes.

Conclusion
A literature review of ECT and neurologic deficits showed that most neurologic deficits resolve within 30 min of ECT. Case reports of prolonged deficits are rare and there are no prior reports of acute MRI changes related to ECT. Thus, the acute deterioration and MRI findings in this patient are likely related to the underlying CACNA1a channelopathy disorder with ECT as a precipitating event. This case report suggests care should be taken when using ECT in patients with pathogenic variants in CACNA1a. Furthermore, it reinforces the utility and importance of expanded genetic testing in patients with neurodevelopmental disorders as findings can provide valuable information that can guide treatment decisions.
Partnership, living arrangements, and low birth weight: evidence from a population-based study on Spanish mothers
Authors: Dello Iacono Chiara , Requena Miguel , Stanek Mikolaj 
Published: December 2022

AbstractBackgroundBirth weight is considered a crucial indicator of individual and population health, as it determines a newborn’s growth and development. An extensive body of research has explored various determinants of perinatal health, including the impact of living arrangements. This population-based study analyzes the relationship between mothers’ partnership status and household structure and children’s low birth weights. It addresses two basic research objectives: on one hand, how living/not living in a couple affects birth weight; on the other, how partnership status impact on birthweight when mothers live in extended households with other non-nuclear members.MethodsA novel database provided by the Spanish Office for National Statistics (INE), which links the 2011 census with births registered from 2011 to 2015 (sample size 22,433) is used. Llogistic regression models are estimated tto obtain adjusted odds ratios (OR) for the relative effects of living arrangements and other covariates such as characteristics of births and mothers’ socioeconomic profiles, on birth weight.ResultsDifferences in low-birth-weight rates may be attributed to the dissimilar socio-demographic characteristics of the groups of mothers in the different coresidential situations. Although our models revealed that the impact of the covariates on birth weight was similar to that shown by previous studies, this was not the case for the effect of the main explanatory variable. Contrary to expectations, the presence/absence of a male partner in nuclear or in extended households does not reveal significant protection against low birth weight. Children born in households in which the male partner was absent were not more likely to have a low birth weight. On the other hand, analyzing the possible protective effect of extended households, we did not detect significant differences in the likelihood of low birth weight between single mothers without and with non-nuclear coresidents in their households.ConclusionsOur analysis provides novel evidence regarding the effect of partnership status and household type on perinatal health in Spain. First, contrary to what has been observed in previous studies in Spain and elsewhere, our study shows that living without a partner has no effect on low birth weight. Second, we reveal that households including non-nuclear coresidents are associated with low birth weight suggesting that even in a basically familist societal context such as the Spanish one, the extended family does not fully protect against poor perinatal outcomes.
Time to first antenatal care booking and its determinants among pregnant women in Ethiopia: survival analysis of recent evidence from EDHS 2019
Authors: kitaw Tegene Atamenta , Haile Ribka Nigatu 
Published: December 2022

Abstract

Background
Antenatal care is one of the components of the maternal and child continuum of care. Timely booking ANC during pregnancy is of utmost importance to guarantee the best possible health outcomes for women and children. Inappropriate timing of the first ANC booking is associated with poor pregnancy outcomes, including perinatal death, stillbirth, and early neonatal death. According to WHO focused ANC recommendation, every mother should start booking ANC within the first 12 weeks of gestational age. However, in developing countries, including Ethiopia, many pregnant mothers were not booking ANC at the recommended time. Thus, this study aims to assess the time to first ANC booking and its determinants in Ethiopia.

Methods
A survival analysis was conducted to determine time to first ANC booking among 3917 weighted study subjects. The data were extracted from EDHS 2019 using STATA version 17 software. A Kaplan Meier survivor curve was computed to estimate the time of first ANC booking. A Long-rank test was used to compare the difference in survival curves. Weibull Inverse Gaussian shared frailty model was used to identify significant predictors. On multivariable analysis, variables having a p-value of ≤ 0.05 are considered statistically significant.

Results
The overall median survival time was four months. The significant determinant of time to first ANC booking are residence (rural [ϕ = 1.111, 95CI: 1.060, 1.164), mother educational level (primary education [ϕ = 0.945, 95CI: 0.915, 0.977], secondary and above educational [ϕ = 0.857, 95CI: 0.819, 0.896]) and wealth index (middle [0.948 (ϕ = 0.948, 95CI: 0.911, 0.986) and rich [ϕ = 0.904, 95CI: 0.865, 0.945])

Conclusion
The median time for first ANC booking is 4 month, which is higher than the WHO recommended time. The timing of the first ANC booking in Ethiopia was mainly influenced by the residence of women, mother educational level, and wealth index. It is strongly recommended to expose mothers to educational materials and other awareness-creation campaigns, as well as to support disadvantaged women, such as the uneducated, poor, and those living in rural or remote areas.
PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry
Authors: Pagadala Meghana S. , Linscott Joshua A. , Talwar James V. , Seibert Tyler M. , Rose Brent , Lynch Julie , Panizzon Matthew , Hauger Richard , Hansen Moritz H. , Sammon Jesse D. , Hayn Matthew H. , Kader Karim , Carter Hannah , Ryan Stephen T. 
Published: December 2022

Abstract
Background
Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance.

Methods
African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis.

Results
We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry.

Conclusions
African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies.
Case presentation of 8-year follow up of recurrent malignant duodenal Insulinoma and lymph node metastases and literature review of malignant Insulinoma management
Authors: Walker Michelle P. , Shenoy Vikram , Metz David C. , Stanley Charles A. , Fraker Douglas , Chandrasekhara Vinay , Amaro Anastassia 
Published: December 2022

Abstract
Background
Insulinoma is an uncommon insulin-secreting neuroendocrine tumor that presents with severe recurrent hypoglycemia. Although cases of extrapancreatic insulinomas have been reported, the majority of insulinomas occur in the pancreas. The number of reported cases of ectopic insulinomas with follow-up assessments is limited and they do not report disease recurrence. The current report presents the first documented case of recurrent extrapancreatic insulinoma with 8 years of follow-up, provides relevant literature review, and proposes surveillance and treatment strategies.

Case presentation
We describe an insulinoma localized in the duodenal wall of a 36-year-old female who presented in 2013 with weight gain and Whipple’s triad and was successfully managed with duodenotomy and enucleation. She presented again in 2017 with recurrent Whipple’s triad and was found to have metastatic disease localized exclusively to peripancreatic lymph nodes. Primary pancreatic insulinoma was not evident and her hypoglycemia resolved following lymph node dissection. Eight years after initial presentation continuous glucose monitoring (CGM) showed a trend for euglycemia, and PET-CT Gallium 68 DOTATATE scan evaluation indicated absence of recurrent disease.

Conclusion
Insulinomas are rare clinical entities and extrapancreatic insulinomas are particularly uncommon. Follow-up evaluation and treatment strategies for ectopic insulinoma recurrence presents a significant clinical challenge as the condition has hitherto remained undescribed in the literature. Available evidence in the literature indicates that lymph node metastases of intrapancreatic insulinomas likely do not change prognosis. Given the absence of long-term data informing the management and monitoring of patients with extrapancreatic insulinoma, we suggest patient education for hypoglycemic symptoms, monitoring for hypoglycemia with CGM, annual imaging, and a discussion with patients regarding treatment with octreotide or alternative somatostatin receptor analog therapies.
Clinical characteristics of patients with unexplainable hypothalamic disorder diagnosed by the corticotropin-releasing hormone challenge test: a retrospective study
Authors: Hataya Yuji , Okubo Marie , Hakata Takuro , Fujimoto Kanta , Iwakura Toshio , Matsuoka Naoki 
Published: December 2022

Abstract
Background
The corticotropin-releasing hormone (CRH) challenge test can distinguish the disorders of the hypothalamus from those of the pituitary. However, the pathophysiology of hypothalamic disorder (HD) has not been fully understood. This study aimed to elucidate the clinical characteristics of patients with unexplainable HD, diagnosed by the CRH challenge test.

Methods
We retrospectively reviewed patients who underwent the CRH challenge test. Patients were categorized into four groups as follows: patients with peak serum cortisol ≥18 μg/dL were assigned to the normal response (NR) group (n = 18), among patients with peak serum cortisol < 18 μg/dL and peak adrenocorticotropic hormone (ACTH) increase ≥two-fold, patients without obvious background pathology were assigned to the unexplainable-HD group (n = 18), whereas patients with obvious background pathology were assigned to the explainable-HD group (n = 38), and patients with peak serum cortisol < 18 μg/dL and peak ACTH increase <two-fold were assigned to the pituitary disorder (PD) group (n = 15). Inter-group comparisons were performed based on clinical characteristics.

Results
In the CRH challenge test, the peak plasma ACTH levels were significantly lower in the unexplainable-HD group than in the NR group, despite more than two-fold increase compared to basal levels. The increase in serum cortisol was significantly higher in the unexplainable-HD group than in the explainable-HD and PD groups. Although patients in the unexplainable-HD group showed a clear ACTH response in the insulin tolerance test, some patients had peak serum cortisol levels of < 18 μg/dL. Furthermore, attenuated diurnal variations and low normal levels of urinary free cortisol were observed. Most patients in the unexplainable-HD group were young women with chronic fatigue. However, supplementation with oral hydrocortisone at physiological doses reduced fatigue only in some patients.

Conclusions
Patients with unexplainable HD diagnosed by the CRH challenge test had hypothalamic–pituitary–adrenal (HPA) axis dysfunction and some patients had mild central adrenal insufficiency. Hydrocortisone supplementation reduced fatigue only in some patients, suggesting that HPA axis dysfunction may be a physiological adaptation. Further investigation of these patients may help elucidate the pathophysiology of myalgic encephalitis/chronic fatigue syndrome.
Starting a Swedish national quality registry for orthognathic surgery: a tool for auditing fundamentals of care
Authors: Sjöström Mats , Lund Bodil , Sunzel Bo , Bengtsson Martin , Magnusson Mikael , Rasmusson Lars 
Published: December 2022

Abstract
Background
National quality registries (NQRs) provide open data for user-directed acquisition. National Quality Registry (NQR) data are often used to analyze the rates of treatment success and adverse events for studies that aim to improve treatment quality and patient satisfaction. Thus, NQRs promote the goal of achieving evidence-based therapies. However, the scientific literature seldom focuses on the complex process of initiating, designing, and implementing an NQR. Starting an NQR may be particularly challenging in a setting where specialized care is decentralized, such as orthognathic surgery in Sweden. The present study describes the initiation and early phases of a new NQR for orthognathic surgery in Sweden.

Methods
The initial inventory phase included gaining knowledge on regulations, creating economic plans, and identifying pitfalls in existing NQRs. Next, a crude framework for the registry was achieved. Outcome measures were selected with a nation-wide questionnaire, followed by a Delphi-like process for selecting parameters to include in the NQR. Our inclusive process comprised a stepwise introduction, feedback-based modifications, and preparatory educational efforts. Descriptive data were collected, based on the first 2 years (2018–2019) of registry operation.

Results
Two years after implementation, 862 patients that underwent 1320 procedures were registered. This number corresponded to a 91% coverage rate. Bimaxillary treatments predominated, and the most common were a Le Fort I osteotomy combined with a bilateral sagittal split osteotomy (n = 275). Reoperations were conducted in 32 patients (3.6%), and the rate of patient satisfaction was 95%.

Conclusions
A National Quality Registry should preferentially be started and maintained by an appointed task force of active clinicians. A collaborative, transparent, inclusive process may be an important factor for achieving credibility and high coverage, particularly in a decentralized setting.