Are all fibrinogen concentrates the same? The effects of two fibrinogen therapies in an afibrinogenemic patient and in a fibrinogen deficient plasma model. A clinical and laboratory case report.

The choice of treatments for inherited, or acquired, fibrinogen deficient states is expanding and there are now several fibrinogen concentrate therapies commercially available. Patients with the rare inherited bleeding disorder, afibrinogenemia, commonly require life-long replacement therapy with fibrinogen concentrate to prevent hemorrhagic complications. Recent reports in the setting of acquired bleeding, namely trauma hemorrhage, have highlighted the potential importance of the different compositions of fibrinogen supplements, including cryoprecipitate and the various plasma- derived concentrates. Clot strength and the subsequent susceptibility of a clot to lysis is highly dependent on the amount of fibrinogen as well as its structural composition, the concentration of pro- and anti-coagulant factors, as well as fibrinolytic regulators, such as factor XIII (FXIII). This report details the effects of two commercially available fibrinogen concentrates (Riastap®, CSL Behring and Fibryga®, Octapharma) on important functional measures of clot formation and lysis in a patient with afibrinogenemia. Our report offers insights into the differential effects of these concentrates, at the clot level, according to the variable constituents of each product, thereby emphasizing that the choice of fibrinogen concentrate can influence the stability of a clot in vivo. Whether this alters clinical efficacy is yet to be understood.

Community-based person-centred integrated care (PIC) networks for healthy ageing in place: a scoping review protocol.

INTRODUCTION: The economic case for preventive care delivered in or near citizens' homes is strong, and there is growing evidence of the role of local-level support in supporting people's health and well-being as they age. However, effective and consistent delivery of person-centred integrated care (PIC) at the community level remains elusive. Previous systematic reviews have focused on specific processes such as case management, but none have focused on the operational delivery of community-based care networks. In this study, we aim to identify what practice-based models of PIC networks exist at the local/neighbourhood level and what evidence is available as to their effectiveness for healthy ageing in place. METHODS AND ANALYSIS: We will undertake a scoping review following the framework proposed by Arksey and O'Malley and updated guidance by the Joanna Briggs Institute. Peer-reviewed sources will be identified through searches of seven databases, and relevant grey literature will be identified through websites of policy and voluntary sector organisations focused on integrated care and/or healthy ageing. Data from included studies will be extracted for relevance to the research questions, including aims and anticipated outcomes of network models, financial and management structures of networks, and evidence of evaluation. Summary tables and narrative comparisons of key PIC network features across settings will be presented. ETHICS AND DISSEMINATION: As no primary data will be collected, ethical approval is not required to conduct this scoping review. In addition to publication as a peer-reviewed article, the results of this review will be summarised as shorter discussion papers for use in follow-up research.

Feasibility and Usability of a Mobile App-Based Interactive Care Plan for Migraine in a Community Neurology Practice: Development and Pilot Implementation Study.

BACKGROUND: Migraine is a common and major cause of disability, poor quality of life, and high health care use. Access to evidence-based migraine care is limited and projected to worsen. Novel mobile health app-based tools may effectively deliver migraine patient education to support self-management, facilitate remote monitoring and treatment, and improve access to care. The risk that such an intervention may increase the care team workload is a potential implementation barrier. OBJECTIVE: This study aims to describe a novel electronic health record-integrated mobile app-based Migraine Interactive Care Plan (MICP) and evaluate its feasibility, usability, and impact on care teams in a community neurology practice. METHODS: Consecutive enrollees between September 1, 2020, and February 16, 2022, were assessed in a single-arm observational study of usability, defined by 74.3% (127/171) completing ≥1 assigned task. Task response rates, rate and type of care team escalations, and patient-reported outcomes were summarized. Patients were prospectively recruited and randomly assigned to routine care with or without the MICP from September 1, 2020, to September 1, 2021. Feasibility was defined by equal to or fewer downstream face-to-face visits, telephone contacts, and electronic messages in the MICP cohort. The Wilcoxon rank-sum test was used to compare continuous variables, and the chi-square test was used for categorical variables for those with at least 3 months of follow-up. RESULTS: A total of 171 patients were enrolled, and of these, 127 (74.3%) patients completed ≥1 MICP-assigned task. Mean escalations per patient per month was 0.9 (SD 0.37; range 0-1.7). Patient-confirmed understanding of the educational materials ranged from 26.6% (45/169) to 56.2% (95/169). Initial mean headache days per week was 4.54 (SD 2.06) days and declined to 2.86 (SD 1.87) days at week 26. The percentage of patients reporting favorable satisfaction increased from a baseline of 35% (20/57) to 83% (15/18; response rate of 42/136, 30.9% to 28/68, 41%) over the first 6 months. A total of 121 patients with MICP were compared with 62 patients in the control group. No differences were observed in the rate of telephone contacts or electronic messages. Fewer face-to-face visits were observed in the MICP cohort (13/121, 10.7%) compared with controls (26/62, 42%; P<.001). CONCLUSIONS: We describe the successful implementation of an electronic health record-integrated mobile app-based care plan for migraine in a community neurology practice. We observed fewer downstream face-to-face visits without increasing telephone calls, medication refills, or electronic messages. Our findings suggest that the MICP has the potential to improve patient access without increasing care team workload and the need for patient input from diverse populations to improve and sustain patient engagement. Additional studies are needed to assess its impact in primary care.

Fishing for subsistence constitutes a livelihood safety net for populations dependent on aquatic foods around the world.

Fishing for subsistence constitutes a livelihood safety net for poverty, malnutrition and gender inequality for populations dependent upon aquatic foods around the world. Here we provide global estimates showing that almost the same amount of small-scale fishers engage in subsistence fishing at some point during the year as in commercial employment and use subsistence estimates to measure small-scale fisheries' livelihood safety net function. In 2016, we estimate that 52.8 million people were engaged in subsistence fishing at some point during the year, while another 60.2 million people were commercially employed (90% of global fisheries employment). From 14 country case studies, it was possible to estimate that the subsistence catch provided an average apparent intake of six nutrients critical for positive health outcomes, equivalent to 26% of the recommended daily nutrient intake for 112.5 million people, higher than the national average contribution of beef or poultry.

Researchers' responsibility to uphold Indigenous rights.

Too often research brings harm to Indigenous peoples.

Apraxia of speech with phonological alexia and agraphia following resection of the left middle precentral gyrus: illustrative case.

BACKGROUND: Apraxia of speech is a disorder of speech-motor planning in which articulation is effortful and error-prone despite normal strength of the articulators. Phonological alexia and agraphia are disorders of reading and writing disproportionately affecting unfamiliar words. These disorders are almost always accompanied by aphasia. OBSERVATIONS: A 36-year-old woman underwent resection of a grade IV astrocytoma based in the left middle precentral gyrus, including a cortical site associated with speech arrest during electrocortical stimulation mapping. Following surgery, she exhibited moderate apraxia of speech and difficulty with reading and spelling, both of which improved but persisted 6 months after surgery. A battery of speech and language assessments was administered, revealing preserved comprehension, naming, cognition, and orofacial praxis, with largely isolated deficits in speech-motor planning and the spelling and reading of nonwords. LESSONS: This case describes a specific constellation of speech-motor and written language symptoms-apraxia of speech, phonological agraphia, and phonological alexia in the absence of aphasia-which the authors theorize may be attributable to disruption of a single process of "motor-phonological sequencing." The middle precentral gyrus may play an important role in the planning of motorically complex phonological sequences for production, independent of output modality.

Development and acceptability of a mobile health application integrated with the electronic heath record for treatment of chronic insomnia disorder.

STUDY OBJECTIVES: To describe the development and feasibility of a cognitive behavioral therapy for insomnia (CBT-I) program delivered via personal digital devices and fully integrated with the electronic health record (EHR). METHODS: A multidisciplinary team of clinicians and members of our Center for Digital Health collaborated to develop a Chronic Insomnia Interactive Care Plan (ChI-ICP), an application that provides personalized and just in time education and promotes self-management using CBT-I concepts, and is activated from and fully integrated into the EHR. Following development, we evaluated patient engagement and workflows, assessed changes to provider workload, and examined outcomes on measures of insomnia during a pilot deployment of the application. RESULTS: A total of 222 patients were enrolled and 179 engaged with the plan during the 3-month pilot program. Enrolled patients generated an average of 3.9 ± 2.3 In Basket messages, most being automated notifications related to noncompletion of assigned tasks, while only a few were related to patients requesting additional training or help with insomnia. Sleep efficiency improved from baseline until the completion of the program from 74.5% ± 16.7% to 87.6% ± 10.8% (P = .001), and the Insomnia Severity Index improved from 14.9 ± 5.22 to 11.6 ± 4.80 (P = .006). CONCLUSIONS: In this pilot implementation of an integrated ChI-ICP, patient engagement was favorable, workflows and workload were not significantly burdensome for the care teams, and initial evaluation of efficacy was favorable. This provides evidence for an application that is a scalable method to assist patients with chronic insomnia and future work should assess its efficacy in controlled trials. CITATION: Morgenthaler TI, Kolla BP, Anderson SE, et al. Development and acceptability of a mobile health application integrated with the electronic heath record for treatment of chronic insomnia disorder. J Clin Sleep Med. 2022;18(12):2785-2792.

The impact of son or daughter care on Chinese older adults' mental health.

RATIONALE: The traditional cultural norm in China is that eldercare should be offered by a son and his family. However, several decades of family planning policies and rapid economic growth have led to low fertility rates, urbanisation, and cultural change, resulting in both reduced household size and the availability of sons. The traditional eldercare system is thus being challenged, especially in urban areas, with an increasing number of daughters supporting their parents, enabled by rising female empowerment, formal economic employment and improved financial capacities. Existing studies examine and compare the amount and types of support provided by sons and daughters, but very little is known about the differential health outcomes of parents experiencing eldercare offered by sons and by daughters. OBJECTIVE: This study investigates the difference in mental health outcomes of parents who receive eldercare from their sons and from their daughters. METHOD: We analyse waves 2013, 2015, and 2018 of the China Health and Retirement Longitudinal Study, with mental health measured by a 10-item Center for Epidemiological Studies-Depression (CES-D-10) score. We compare the CES-D-10 score between parents with different sources of care - son's family, daughter's family or other - with multivariate statistical analysis. RESULTS: Receiving regular care from a son (or a daughter-in-law) is associated with a lower CES-D score than from a daughter (or a son-in-law). The difference mainly exists amongst those with a stronger son preference and those who are heavily deponent on their children, in particular rural parents, mothers, and those with less wealth. CONCLUSION: Our study explores the evidence on mental health inequalities among parents with different sources of care, highlighting that lack of son care creates an apparent mental health disadvantage. Lowering older adults' dependency on their children may alleviate this inequality by improving their financial independence. We also suggest the development of a long-term care system and greater facilitation of older adults to take-up supplementary services for family care.

Pregnancy and the Singing Voice: A Survey of What Singers Report.

Pregnancy has profound effects on a variety of body systems by way of hormonal and physical changes. Many of these changes directly affect body systems involved in singing. Assumptions exist about what can happen to a person's voice during pregnancy, but these assumptions are based on theoretical predictions leaving little knowledge of the lived experiences of voice changes during pregnancy. An anonymous mixed-method survey was given to 321 professional singers to gain insights on the lived experiences of pregnant singers. This investigation explored what people were told about the effects of pregnancy on the voice in comparison to what they actually experienced. Results show that about half of the respondents' experience matched what they were told for respiration. For phonation and vocal quality less than 25% respondent's experience matched what they were told. In addition, most of the information respondents received came from friends, colleagues, and teachers compared to medical professionals suggesting a need for more interdisciplinary education to best prepare vocalists who are contemplating becoming pregnant.

A multispeaker dataset of raw and reconstructed speech production real-time MRI video and 3D volumetric images.

Real-time magnetic resonance imaging (RT-MRI) of human speech production is enabling significant advances in speech science, linguistics, bio-inspired speech technology development, and clinical applications. Easy access to RT-MRI is however limited, and comprehensive datasets with broad access are needed to catalyze research across numerous domains. The imaging of the rapidly moving articulators and dynamic airway shaping during speech demands high spatio-temporal resolution and robust reconstruction methods. Further, while reconstructed images have been published, to-date there is no open dataset providing raw multi-coil RT-MRI data from an optimized speech production experimental setup. Such datasets could enable new and improved methods for dynamic image reconstruction, artifact correction, feature extraction, and direct extraction of linguistically-relevant biomarkers. The present dataset offers a unique corpus of 2D sagittal-view RT-MRI videos along with synchronized audio for 75 participants performing linguistically motivated speech tasks, alongside the corresponding public domain raw RT-MRI data. The dataset also includes 3D volumetric vocal tract MRI during sustained speech sounds and high-resolution static anatomical T2-weighted upper airway MRI for each participant.

Societal Need for Interdisciplinary Ageing Research: An International Alliance of Research Universities "Ageing, Longevity and Health" Stream (IARU-ALH) Position Statement.

Ageing is a global concern with major social, health, and economic implications. While individual countries seek to develop responses to immediate, pressing needs, international attention and collaboration is required to most effectively address the multifaceted challenges and opportunities an ageing global population presents in the longer term. The Ageing, Longevity and Health stream of the International Alliance of Research Universities (IARU-ALH) was built on a solid foundation of first-class interdisciplinary research and on innovative outreach and communication centres. This interdisciplinary network conducts projects that span biology, medicine, social sciences, epidemiology, public health, policy, and demography, and actively engages with the public and other societal stakeholders. Here we posit that such international interdisciplinary networks are needed and uniquely placed to address major challenges related to health and ageing and ultimately will produce new understanding and knowledge to promote the awareness of healthy ageing and encourage societal change via novel, science-informed interventions. Global interdisciplinary research presents great potential and opportunities to accelerate our understanding of human ageing and to produce new, more effective solutions to a pressing, complex problem. However, more focused, strategic efforts and investments are required in order to deliver on these potentials and reap maximum benefits for individuals and societies. IARU-ALH members are determined to contribute, in collaboration with others, to delivering on this vision.

Characterisation of a novel thrombomodulin c.1487delC,p.(Pro496Argfs*10) variant and evaluation of therapeutic strategies to manage the rare bleeding phenotype.

INTRODUCTION: A novel variant in the thrombomodulin (TM) gene, c.1487delC,p.(Pro496Argfs*10), referred to as Pro496Argfs*10, was identified in a family with an unexplained bleeding disorder. The Pro496Argfs*10 variant results in loss of the transmembrane and intracellular segments of TM and is associated with an increase in soluble TM (sTM) in the plasma. The aim of this study was to characterise the effect of elevated sTM on thrombin generation (TG) and fibrinolysis, and to evaluate therapeutic strategies to manage the patients. METHODS: Plasma samples were obtained from two patients carrying the variant. TG was triggered using 5 pM tissue factor and measured using the Calibrated Automated Thrombogram. A turbidity clot lysis assay was used to monitor fibrinolysis. TM antigen was quantified by ELISA. RESULTS: Patients with the Pro496Argfs*10 variant had significantly elevated plasma sTM compared to controls (372.6 vs. 6.0 ng/ml). TG potential was significantly lower in patients but was restored by inhibition of activated protein C (APC) or addition of activated Factor VII (FVIIa) or platelet concentrates. In vitro experiments suggested that activated prothrombin complex concentrates (APCC) posed a risk of thrombosis. The time to 50% lysis was significantly prolonged in patients compared to controls, 69.7 vs. 42.3 min. Clot lysis time was shortened by inhibition of activated thrombin activatable fibrinolysis inhibitor (TAFIa). CONCLUSIONS: Our data demonstrate that increased sTM enhances APC generation and reduces TG. Simultaneously, the rate of fibrinolysis is delayed due to increased TAFI activation by sTM. Treatment with platelet or FVIIa concentrates may be beneficial to manage this rare bleeding disorder.

Employment trajectories and health: cohort differences in English and French women.

BACKGROUND: Policy and social change have increased women's participation in the labour market and their opportunity to combine paid work with family care. We analyse whether a specific combination of employment and domestic duties over the life course are associated with variations in English and French women's health, focusing on two birth cohorts. METHODS: We used sequence analysis to group women in English Longitudinal Study of Ageing and Survey of Health, Ageing and Retirement in Europe, according to their work and family histories. Using ordered logistic regression, we tested for group differences in later self-reported health and depressive symptoms, while controlling for a range of adult socio-economic circumstances. RESULTS: The findings confirm important differences between birth cohorts and countries. French women report a higher risk of poor self-reported health and mental issues than English women. Full-time domestic duties were particularly deleterious for the health of the two younger cohorts, whereas a combination of employment and domestic duties across the life course had a positive association with later-life health. DISCUSSION: Further research is needed to explore the mechanisms linking work and care trajectories to poor health.

Son or Daughter Care in Relation to Self-Reported Health Outcomes for Older Adults in China.

OBJECTIVES: Parental care in China is traditionally provided by sons. In recent decades-partly due to the One-Child Policy but also economic development and urbanization-significant changes have occurred with more and more parents receiving care from daughters. We investigate the disparities in outcomes of eldercare provided by son(s) and daughter(s). METHODS: Our study compares the self-reported health (SRH) status of parents who receive eldercare from daughters and sons in China, analyzing the harmonized 2013, 2015, and 2018 waves of CHARLS with random-effects logistic estimates. RESULTS: Our results show that the SRH status of parents who receive care from their sons is greater than those cared for by their daughters. This disparity is greater in rural areas, for mothers, and poorer families. DISCUSSION: The One-Child Policy was more effective in urban areas, reducing both the availability of sons and cultural son preference. Higher levels of education received by girls in urban settings increases their employability and thus their ability to materially care for their parents. However, traditional norms and gender differences in social economic statuses still persist in rural areas, leading to higher SRH status of those cared for by sons, especially amongst those who are heavily dependent on their children: mothers or parents with less wealth.

Variability in individual constriction contributions to third formant values in American English /ɹ/.

Although substantial variability is observed in the articulatory implementation of the constriction gestures involved in /ɹ/ production, studies of articulatory-acoustic relations in /ɹ/ have largely ignored the potential for subtle variation in the implementation of these gestures to affect salient acoustic dimensions. This study examines how variation in the articulation of American English /ɹ/ influences the relative sensitivity of the third formant to variation in palatal, pharyngeal, and labial constriction degree. Simultaneously recorded articulatory and acoustic data from six speakers in the USC-TIMIT corpus was analyzed to determine how variation in the implementation of each constriction across tokens of /ɹ/ relates to variation in third formant values. Results show that third formant values are differentially affected by constriction degree for the different constrictions used to produce /ɹ/. Additionally, interspeaker variation is observed in the relative effect of different constriction gestures on third formant values, most notably in a division between speakers exhibiting relatively equal effects of palatal and pharyngeal constriction degree on F3 and speakers exhibiting a stronger palatal effect. This division among speakers mirrors interspeaker differences in mean constriction length and location, suggesting that individual differences in /ɹ/ production lead to variation in articulatory-acoustic relations.