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Michael Wang,1,* Claude Negrier,2,* Frank Driessler,3,* Clifford Goodman,4,* Mark W Skinner5,6,* 1University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 2National Reference Center for Haemophilia, Louis Pradel Cardiology Hospital, University of Lyon, Lyon, France; 3Bayer, Basel, Switzerland; 4The Lewin Group, Falls Church, VA, USA; 5Institute for Policy Advancement Ltd, Washington, DC, USA; 6McMaster University, Hamilton, ON, Canada*These authors contributed equally to this workCorrespondence: Frank Driessler, Bayer AG, Peter Merian Straße 84, Basel, CH-4052, Switzerland, Tel +41 79 422 32 18, Email frank.driessler@bayer.comPurpose: The anticipated emergence of hemophilia gene therapy will present people with hemophilia (PWH) and treating clinicians with increasingly complex treatment options. It will be critical that PWH and their families be empowered to participate fully in decision-making through transparent communication and the development of targeted educational resources.Methods: The Council of Hemophilia Community (CHC) convened across a series of roundtable meetings to define the patient journey for hemophilia gene therapy, and to develop a question-and-answer style resource to guide discussion between healthcare professionals (HCPs) and their patients. Patient groups were also consulted during the development of this tool.Results: The CHC defined 5 key stages in the hemophilia gene therapy patient journey: pre-gene therapy (information-seeking and decision-making), treatment initiation, short- and long-term post-gene therapy follow-up. PWH will have different questions and concerns at each stage of their journey, which should be discussed with their HCP to aid decision-making. The resulting patient journey infographic and Q&A resource (see Supplementary Materials) has been developed for HCPs and PWH to provide a novel and practical roadmap of key issues and considerations throughout all stages.Conclusion: These resources support a collaborative, patient-centric, shared decision-making approach to inform treatment decision discussions between HCPs and PWH. The value of such discussions will be influenced by the language adopted; health literacy is a particularly important consideration, and these discussions should be accessible and tailored to PWH. HCPs and PWH can benefit from awareness of the common questions and uncertainties as they progress together along the patient journey. While the contents of this article are specific to hemophilia gene therapy, the concepts developed here could be adapted to aid patients in other disease states.Keywords: hemophilia, patients, HCP guidance, health literacy, disease awareness, treatment landscape

Intra-articular infusion of local anaesthetic after joint arthroplasty is attractive in that it is simple and will not cause motor block. However the efficacy of the technique has yet to be established. We enrolled 66 patients scheduled for unilateral total knee arthroplasty under general anaesthesia and single-shot femoral and sciatic nerve blocks. All patients had an intra-articular Painbuster device sited at the end of the procedure. Patients were then randomised to control or one of two treatment arms - low-dose and high-dose ropivacaine. In the control group the balloon was filled with saline, in the low-dose group with 0.2% ropivacaine and in the high-dose group 0.375% ropivacaine. The catheters were infused continuously for 48 hours and then removed. Patients were followed up daily for three days to determine pain scores, opioid consumption and subjective assessment of the analgesic efficacy of the catheter Data were analysed for 30 controls and 31 in the treatment arms. Both groups were similar There were no significant differences between the control and treatment groups at all time points after adjustment for age. Patients in the high-dose group had higher pain scores and higher opioid consumption than the control groups from 24 to 48 hours. There were two cases of infection, both in the treatment groups. No positive benefit of intra-articular infusion of local anaesthetic after total knee arthroplasty could be identified. On the contrary there may be negative effects in terms of expense, pain and possibly infection risks. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of bilateral amplification is now common clinical practice for hearing aid users but not for cochlear implant recipients. In the past, most cochlear implant recipients were implanted in one ear and wore only a monaural cochlear implant processor. There has been recent interest in benefits arising from bilateral stimulation that may be present for cochlear implant recipients. One option for bilateral stimulation is the use of a cochlear implant in one ear and a hearing aid in the opposite nonimplanted ear (bimodal hearing). PURPOSE: This study evaluated the effect of wearing a cochlear implant in one ear and a digital hearing aid in the opposite ear on speech recognition and localization. RESEARCH DESIGN: A repeated-measures correlational study was completed. STUDY SAMPLE: Nineteen adult Cochlear Nucleus 24 implant recipients participated in the study. INTERVENTION: The participants were fit with a Widex Senso Vita 38 hearing aid to achieve maximum audibility and comfort within their dynamic range. DATA COLLECTION AND ANALYSIS: Soundfield thresholds, loudness growth, speech recognition, localization, and subjective questionnaires were obtained six-eight weeks after the hearing aid fitting. Testing was completed in three conditions: hearing aid only, cochlear implant only, and cochlear implant and hearing aid (bimodal). All tests were repeated four weeks after the first test session. Repeated-measures analysis of variance was used to analyze the data. Significant effects were further examined using pairwise comparison of means or in the case of continuous moderators, regression analyses. The speech-recognition and localization tasks were unique, in that a speech stimulus presented from a variety of roaming azimuths (140 degree loudspeaker array) was used. RESULTS: Performance in the bimodal condition was significantly better for speech recognition and localization compared to the cochlear implant-only and hearing aid-only conditions. Performance was also different between these conditions when the location (i.e., side of the loudspeaker array that presented the word) was analyzed. In the bimodal condition, the speech-recognition and localization tasks were equal regardless of which side of the loudspeaker array presented the word, while performance was significantly poorer for the monaural conditions (hearing aid only and cochlear implant only) when the words were presented on the side with no stimulation. Binaural loudness summation of 1-3 dB was seen in soundfield thresholds and loudness growth in the bimodal condition. Measures of the audibility of sound with the hearing aid, including unaided thresholds, soundfield thresholds, and the Speech Intelligibility Index, were significant moderators of speech recognition and localization. Based on the questionnaire responses, participants showed a strong preference for bimodal stimulation. CONCLUSIONS: These findings suggest that a well-fit digital hearing aid worn in conjunction with a cochlear implant is beneficial to speech recognition and localization. The dynamic test procedures used in this study illustrate the importance of bilateral hearing for locating, identifying, and switching attention between multiple speakers. It is recommended that unilateral cochlear implant recipients, with measurable unaided hearing thresholds, be fit with a hearing aid. [ABSTRACT FROM AUTHOR]

This paper contributes to the literature on the geographies of care and caregiving by examining the implications of weather for providing home and community care for children and older adults. Integrating research from two previous qualitative studies of formal and informal care provisioning in Ontario, Canada, the authors re-analyzed semi-structured interviews with 83 directors, managers, paid staff, volunteers and family members to examine the challenges they faced when providing care during the winter season. Similar to other settings where winter conditions like snow, ice and cold temperatures are commonplace, the studies were set within a health policy context in which there is not enough recognition of the difficulties of weather for coordinating, managing and providing care to disabled, injured, chronically ill and frail individuals. The re-analysis focused on how winter conditions translate into geographical, administrative, economic, operational, physical, social and psychological barriers within and across different 'scales of care'. The findings indicate that the problems posed by weather are crucial yet often underestimated aspects of home and community care provided by formal and informal caregivers. The analysis of weather-related challenges for care provisioning needs to be extended to other seasonal conditions (e.g., the challenges of delivering care in extreme heat), to the developing world and even to the burgeoning debates on the health implications of global environmental change. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of the increased instantaneous input dynamic range (IIDR) in the Nucleus Freedom cochlear implant (CI) system on recipients' ability to perceive soft speech and speech in noise. Ten adult Freedom CI recipients participated. Two maps differing in IIDR were placed on each subject's processor at initial activation. The IIDR was set to 30 dB for one map and 40 dB for the other. Subjects used both maps for at least one month prior to speech perception testing. Results revealed significantly higher scores for words (50 dB SPL), for sentences in background babble (65 dB SPL), and significantly lower sound field threshold levels with the 40 compared to the 30 dB IIDR map. Ceiling effects may have contributed to non-significant findings for sentences in quiet (50 dB SPL). The Freedom's increased IIDR allows better perception of soft speech and speech in noise. [ABSTRACT FROM AUTHOR]

Thirty 'new' lists of monosyllabic words were created at the University of Melbourne and recorded by Australian and American English speakers. These new lists and the ten original CNC lists (Peterson and Lehiste, 1962) were used during the feasibility study of the Nucleus Research Platform 8 Cochlear Implant System (Holden et al, 2004). Performance was similar across original and new lists for six implanted Australian subjects; for four implanted U.S. subjects, mean performance was 23 percentage points lower with the new than with the original lists. To evaluate differences between original and new lists for the American English recording, 22 CI recipients were administered all 40 CNC lists (30 new and 10 original lists). The overall mean word score for the new lists was significantly lower (22.3 percentage points) than for the original lists. Acoustic analysis revealed that decreased performance was most likely due to reduced amplitudes of certain initial and final consonants. The new CNC lists can be used as more difficult test material for clinical research. [ABSTRACT FROM AUTHOR]

This paper considers how long-term care restructuring, under the rubric of managed competition, has increased pressure on voluntary sector providers of long-term care to elderly populations in small, rural places. Drawing on in-depth interviews with key-informants from non-profit organizations, we present a case study set in rural Ontario to develop a situated understanding of the impact of restructuring on voluntary sector providers of long-term care. We contend that managed competition (underway in Ontario since 1995) has constrained providers, eroded service choices, and reduced access to long-term care in rural areas leaving rural populations more disadvantaged than ever before when it comes to public service provisioning. [ABSTRACT FROM AUTHOR]

Results of studies performed in our laboratory suggest that cochlear implant recipients understand speech best if the following speech processor parameters are individually chosen for each person: minimum and maximum stimulation levels on each electrode in the speech processor program (MAP), stimulation rate, and speech coding strategy. If these and related parameters are chosen to make soft sounds (from approximately 100 to 6,000 Hz) audible at as close to 20 dB hearing level as possible and loud sounds not too loud, recipients have the opportunity to hear speech in everyday life situations that are of key importance to children who are learning language and to all recipients in terms of ease of communication. [ABSTRACT FROM AUTHOR]

With today's technology and the demonstrated success of cochlear implantation, along with expanded candidacy criteria, the opportunity to provide optimal hearing to both ears for individuals with severe-to-profound hearing loss is greater than ever. This article reviews the advantages of binaural hearing and the disadvantages of hearing with only one ear or hearing with two ears with significantly different sound thresholds. A case study is presented that demonstrates the benefit of bimodal hearing (i.e., a cochlear implant [CI] in one ear and a contralateral hearing aid [HA]) in a nontraditional CI candidate with asymmetrical hearing thresholds. Then, selected studies in adult recipients who use a CI and contralateral HA or who use two CIs are summarized. The data overall demonstrate that bilateral CI recipients, traditional bimodal recipients, and nontraditional bimodal recipients experience substantial binaural hearing advantages, including improved speech recognition in noise, localization, and functional everyday communication. These results indicate that bilateral stimulation of the auditory system through a CI and contralateral HA or two CIs is beneficial and should become standard clinical practice. [ABSTRACT FROM AUTHOR]

The choice of frequency boundaries for the analysis channels of cochlear implants has been shown to impact the speech perception performance of adult recipients (Skinner et al, 1995; Fourakis et al, 2004). While technological limitations heretofore have limited the clinical feasibility of investigating novel frequency assignments, the SPEAR3 research processor affords the opportunity to investigate an unlimited number of possibilities. Here, four different assignments are evaluated using a variety of speech stimuli. All participants accommodated to assignment changes, and no one assignment was significantly preferred. The results suggest that better performance can be achieved using a strategy whereby (1) there are at least 7-8 electrodes allocated below 1000 Hz, (2) the majority of remaining electrodes are allocated between 1100-3000 Hz, and (3) the region above 3 kHz is represented by relatively few electrodes (i.e., 1-3). The results suggest that such frequency assignment flexibility should be made clinically available. [ABSTRACT FROM AUTHOR]

Two speech processor programs (MAPs) differing only in electrode frequency boundary assignments were created for each of eight Nucleus 24 Cochlear Implant recipients. The default MAPs used typical frequency boundaries, and the experimental MAPs reassigned one additional electrode to vowel formant regions. Four objective speech tests and a questionnaire were used to evaluate speech recognition with the two MAPs. Results for the closed-set vowel test and the formant discrimination test showed small but significant improvement in scores with the experimental MAP. Differences for the Consonant-Vowel Nucleus-Consonant word test and closed-set consonant test were nonsignificant. Feature analysis revealed no significant differences in information transmission. Seven of the eight subjects preferred the experimental MAP, reporting louder, crisper, and clearer sound. The results suggest that Nucleus 24 recipients should be given an opportunity to compare a MAP that assigns more electrodes in vowel formant regions with the default MAP to determine which provides the most benefit in everyday life. [ABSTRACT FROM AUTHOR]

Introduction: The use of shared decision-making (SDM) in clinical settings is becoming more prevalent. The evolving and increasingly complex treatment landscape of haemophilia management has augmented the need and desire for SDM between patients and their healthcare team. SDM tools have been used in other chronic conditions and can be an effective form of education for patients and clinicians., Aim: The World Federation of Hemophilia (WFH) partnered with people with haemophilia (PWH), patient advocacy groups, and healthcare practitioners to form an expert working group to develop an educational tool for PWH and their caregivers. The primary objectives included educating PWH on the available prophylactic treatments and facilitating discussion between PWH and their healthcare team., Methods: The tool was proposed and developed by the expert working group, workshopped at conference round tables, and evaluated in two focus groups., Results: The interactive WFH SDM Tool guides users through the SDM treatment journey and provides an opportunity for reflection on current disease impact and treatment preferences, educational fact sheets and videos, and a comparison between treatment classes. Two forms of the SDM Tool are available: an online platform with a summary page that may be printed and shared and a printable workbook. All evidence in the tool is based on the prescribing information or phase III clinical trial publications. The Tool will be updated twice each year., Conclusion: The WFH SDM Tool is the first available resource that translates published guidance on SDM in haemophilia into a practical, user-friendly tool aimed at facilitating patient-centred treatment decisions., (© 2024 John Wiley & Sons Ltd.)

Introduction: Currently, no quality-of-life instrument exists that captures the full experience of the mental health outlook (MHO), a coreHEM core outcome, in people with haemophilia, including the potential transformational experience of receiving gene therapy., Aim: To describe the methods used to develop a content validated patient-reported outcome measure (PROM) that measures MHO for people with haemophilia., Methods: A conceptual framework, developed from a literature/evidence review, was used to create an interview guide and draft a questionnaire. Males aged 15 or older with severe/moderate haemophilia were eligible to participate in concept elicitation or cognitive debriefing interviews. The conceptual framework was refined based on a thematic analysis of concept elicitation interviews and PROM items were developed from the conceptual framework. Cognitive debriefing sessions that prioritised relevance and understanding of the PROM were held in two rounds; items were updated iteratively., Results: A conceptual framework with five domains (stigma, anxiety, depression, life interference and identity) was constructed from over 300 identified MHO concepts. Fifty-three participants took part in interviews. After 32 concept elicitation interviews, the framework was updated by including eight new sub-concepts and eliminating two. Updates to the questionnaire included items added or removed and improved wording. The final coreHEM MHO PROM has 26 questions in two sections (general mental health associated with haemophilia, and a gene therapy section)., Conclusions: The instrument is content-validated and can be used as an exploratory outcome. MHO scores can be measured and compared to give more insight into patient quality of life., (© 2024 John Wiley & Sons Ltd.)

Competing Interests: GP is a consultant for Novo Nordisk, Roche, and Sanofi. BO'M has received honoraria or speaking fees from Biomarin, Bayer, and CSL Behring. RK has served on scientific advisory boards for BioMarin and Pfizer and has received research funding from Bayer. MWS’ institution received research support as part of an independent investigator-initiated research project and received research support, honoraria, or fees from Band Therapeutics, Bayer, Biomarin, CSL, Novo Nordisk, Roche/Genentech, Pfizer, Sanofi, Takeda, and Vega Therapeutics. MM received honoraria from Novo Nordisk, Takeda, Sanofi, and Grifols. FP has received honoraria from Takeda and Spark and has served on advisory boards for CSL Behring, BioMarin, Roche, Sanofi, and Sobi. AS has received research grants from Roche, Novo Nordisk, Sanofi, and Pfizer; has had speaker assignments from Sanofi, Novo Nordisk, Roche, Takeda, Pfizer, Sanofi, BioMarin, and Spark; and is on the advisory boards of Sanofi, Novo Nordisk, Roche, Takeda, Pfizer, BioMarin, and Spark.

Centrosomes are the canonical microtubule organizing centers (MTOCs) of most mammalian cells, including spermatocytes. Centrosomes comprise a centriole pair within a structurally ordered and dynamic pericentriolar matrix (PCM). Unlike in mitosis, where centrioles duplicate once per cycle, centrioles undergo two rounds of duplication during spermatogenesis. The first duplication is during early meiotic prophase I, and the second is during interkinesis. Using mouse mutants and chemical inhibition, we have blocked centriole duplication during spermatogenesis and determined that non-centrosomal MTOCs (ncMTOCs) can mediate chromosome segregation. This mechanism is different from the acentriolar MTOCs that form bipolar spindles in oocytes, which require PCM components, including gamma-tubulin and CEP192. From an in-depth analysis, we identified six microtubule-associated proteins, TPX2, KIF11, NuMA, and CAMSAP1-3, that localized to the non-centrosomal MTOC. These factors contribute to a mechanism that ensures bipolar MTOC formation and chromosome segregation during spermatogenesis when centriole duplication fails. However, despite the successful completion of meiosis and round spermatid formation, centriole inheritance and PLK4 function are required for normal spermiogenesis and flagella assembly, which are critical to ensure fertility., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: The Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire is a patient-reported outcome tool that assesses quality of life and disease burden in people with haemophilia (PWH)., Aim: To assesses the test-retest reliability of PROBE when completed using the mobile phone application., Methods: We recruited PWH, including carriers, and individuals with no bleeding disorders who attended haemophilia-related workshops or via social media. Participants completed PROBE three times (twice on the app: T1 and T2, and once on the web, T3). Test-retest reliability was analysed for T1 versus T2 (app to app, time period one) and T2 versus T3 (app to web, time period two)., Results: We enrolled 48 participants (median age = 56 [range 27-78] years). Eighteen participants (37.5%) were PWH and seven (14.6%) were carriers. On general health domain questions, we found almost perfect agreement, except for a question on the frequency of use of pain medication in the last 12 months [Kappa coefficient (κ) .72 and .37 for time period one and two, respectively] and any use of pain medications (κ .75) for time period two. For haemophilia-related questions, we found substantial to perfect agreement, except for the questions on the number of joint bleeds in the previous 6 months for time period one (κ .49) and the number of bleeds in the previous two weeks for time period two (κ .34)., Conclusions: The results demonstrate the reliability of the PROBE app. The app can be used interchangeably with the paper and web platforms for PROBE administration., (© 2024 John Wiley & Sons Ltd.)

Background: Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL)., Objectives: We aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1., Methods: Participant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS). Participants completed the questionnaires at baseline and through 104 weeks postinfusion with 6 × 10 13 vg/kg of valoctocogene roxaparvovec. Scores were analyzed per participant characteristics and outcomes., Results: For 132 HIV-negative participants, mean change from baseline in Haemo-QOL-A Total Score met the anchor-based clinically important difference (CID: 5.5) by week 12; the mean (SD) increase was 7.0 (12.6) at week 104. At week 104, improvement in Consequences of Bleeding, Treatment Concern, Worry, and Role Functioning domain scores exceeded the CID (6). EQ-5D-5L Utility Index scores improved above the CID at week 52, but not at week 104. EQ-5D-5L visual analog scale and HAL scores increased from baseline to week 104. Participants reported less activity and work impairment at week 104 than baseline. Participants with problem joints had lower mean baseline Haemo-QOL-A Total and domain scores than those without them, but improved over 104 weeks, except for 11 participants with ≥3 problem joints. Participants with 0 bleeds during the baseline prophylaxis period reported Haemo-QOL-A score improvements above the CID, including in the Consequences of Bleeding domain., Conclusion: Valoctocogene roxaparvovec provided clinically meaningful HRQOL improvement for men with severe HA., Competing Interests: Declaration of competing interests B.O.M. reports consulting fees from BioMarin Pharmaceutical Inc and Freeline. A.L.D. reports research funding from Sanofi, Takeda, Freeline, BioMarin Pharmaceutical Inc, and the American Thrombosis and Hemostasis Network; consulting fees from BioMarin Pharmaceutical Inc, Genentech/Roche, Kedrion, CSL Behring, and uniQure; and service on the board of the World Federation of Hemophilia USA. A.D.L. reports consulting or advisory panel fees from BioMarin Pharmaceutical Inc, Dova, CSL Behring, Merck, Catalyst, and HEME Biologics; and participation as a clinical trial investigator in trials sponsored by BioMarin Pharmaceutical Inc, Sangamo, and Pfizer. F.P. reports honoraria as a speaker for educational symposia by Grifols, Sanofi, and Takeda and as an advisory member for Sanofi and Roche. M.C.O. reports consulting fees from Bayer, BioMarin Pharmaceutical Inc, Novo Nordisk, Pfizer, Roche, Sanofi, and Takeda; research grants from Pfizer, Roche, and Takeda; service as a clinical trial investigator for BioMarin Pharmaceutical Inc, Novo Nordisk, Pfizer, Roche, Sanofi, and Takeda; speaker honoraria from Bayer, BioMarin Pharmaceutical Inc, Novo Nordisk, Roche, and Takeda; travel support from Novo Nordisk, Roche, and Takeda; and participation in grant reviewing for Grifols. J.M. reports consulting fees from Baxalta, CSL Behring, Catalyst Biosciences, Freeline, LFB, Novo Nordisk, and Spark; research grants from and service as a clinical trial investigator for BioMarin Pharmaceutical Inc, CSL Behring, Novo Nordisk, Pfizer, Sobi, Roche, Novartis, Sanofi, and Unique; and speaker fees from Novo Nordisk, Pfizer, Sanofi, Sobi, Shire, Roche, Takeda, the International Society on Thrombosis and Haemostasis, and the World Federation of Hemophilia. K.P. reports consulting fees and research grants from Sobi, Octapharma, Novo Nordisk, and Pfizer; and served as a clinical trial investigator for uniQure, BioMarin Pharmaceutical Inc, and Roche. J-D.W. reports consulting fees from Bayer, Novo Nordisk, Pfizer, Chugai, Sanofi, Takeda, and Sobi; speaker fees from Bayer, CSL Behring, Novo Nordisk, Pfizer, Chugai, Sanofi, and Takeda; and service as a clinical trial investigator for Bayer, BioMarin Pharmaceutical Inc, Novo Nordisk, Pfizer, Roche/Chugai, and Sanofi. G.L. has received honoraria for participating in educational events from Novartis, LEO, Sobi, Alexion, Takeda, Novo Nordisk, and Sanofi; and consulting fees from UCB. A.G. reports honoraria for service on advisory boards from BioMarin Pharmaceutical Inc, Genentech, Pfizer, Bayer, ATHN, Novo Nordisk, uniQure, and Sanofi Genzyme; and travel grants from BioMarin Pharmaceutical Inc. E.C. reports consulting fees from Genentech, BioMarin Pharmaceutical Inc, Novo Nordisk, Takeda, Sanofi, HEMA Biologics, and CSL Behring; and speaker fees from Genentech. D.P. reports a travel grant from Pfizer. H.C. reports consulting fees from Bayer, BioMarin Pharmaceutical Inc, Roche, and Sobi; served as a clinical trial investigator for BioMarin Pharmaceutical Inc, Bioverativ, CSL Behring, LFB, Octapharma, Roche, Pfizer, Sobi, and Takeda; reports speaker fees from BioMarin Pharmaceutical Inc, Pfizer, Roche, and Sobi; and reports travel grants from BioMarin Pharmaceutical Inc, CSL Behring, Octapharma, Roche, and Sobi. M.F.L.F. reports participation in advisory boards and receiving speaking fees from Shire/Takeda, Amgen, CSL Behring, Novo Nordisk, Bayer, LFB, Pfizer, and Sobi. E.M. reports consulting fees and travel support from BioMarin Pharmaceutical Inc and served as a clinical trial investigator for BioMarin Pharmaceutical Inc. M.W.S. reports consulting fees from Bayer, BioMarin Pharmaceutical Inc, Pfizer (DMC), Roche/Genentech, Sanofi, Spark (DMC), and Takeda; and research grants from BioMarin Pharmaceutical Inc, Freeline, Roche, Takeda, and uniQure. R.Klamroth reports consulting fees from Bayer, Biotest, BioMarin Pharmaceutical Inc, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, and Sobi; research grants from Bayer and LEO; speaker fees from Bayer, Biotest, BioMarin Pharmaceutical Inc, CSL Behring, Daiichi Sankyo, LEO, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, and Sobi; travel support from Bayer, Biotest, BioMarin Pharmaceutical Inc, CSL Behring, Daiichi Sankyo, LEO, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, and Sobi; and service as a clinical trial investigator for Bayer, BioMarin Pharmaceutical Inc, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, Sobi, and uniQure. S.W.P. reports consulting fees from Apcintex, ASC Therapeutics, Bayer, BioMarin Pharmaceutical Inc, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Spark Therapeutics, Takeda, and uniQure; and service as a clinical trial investigator for BioMarin Pharmaceutical Inc, Freeline, Genentech/Roche, Sanofi, and uniQure. J.Q. is a former employee of BioMarin Pharmaceutical and may hold stock. H.Y., T.M.R., and W.Y.W. are employees and stockholders of BioMarin Pharmaceutical Inc. C.W.T., H.T., R.Kazmi, and T-L.K. have no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Despite prior research that examines the spatial and temporal dimensions of older adult care, there is disparate research on the influence of patient flow priorities on older adult care over time and place. Drawing on a qualitative case study of rural older adult transitions in care in the Canadian context we examine how patient flow prioritization undervalues older patients' needs and the local contexts in which care is provided. Certainly, accounting for the spatial and temporal dimensions of older adult care has broader implications that will enhance future research, policy and practice. Policy makers, researchers and clinicians may then use these recommendations as a stepping stone to align the health care system with the older populations that they serve., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The introduction of adeno-associated virus-mediated, liver-directed gene therapy into the hemophilia treatment landscape brings not only great promise but also considerable uncertainty to a community that has a history punctuated by the devastating effects of HIV and hepatitis C virus. These infections were introduced into people with hemophilia through the innovation of factor concentrates in the 1970s and 1980s. Concentrates, heralded as a major advance in treatment at the time, brought devastation and death to the community already challenged by the complications of bleeding into joints, vital organs, and the brain. Over the past 5 decades, considerable advances in hemophilia treatment have improved the survival, quality of life, and participation of people with hemophilia, although challenges remain and health equity with their unaffected peers has not yet been achieved. The decision to take a gene therapy product is one in which an informed, holistic, and shared decision-making approach must be employed. Bias on the part of health care professionals and people with hemophilia must be addressed and minimized. Here, we review data leading to the regulatory authorization of valoctocogene roxaparvovec, an adeno-associated virus 5 gene therapy, in Europe to treat hemophilia A and etranacogene dezaparvovec-drlb in the United States and Europe to treat hemophilia B. We also provide an overview of the decision-making process and recommend steps that should be taken by the hemophilia community to ensure the safety of and optimal outcomes for people with hemophilia who choose to receive a gene therapy product., Competing Interests: Declaration of competing interests R.K. received research funding from Bayer. G.F.P. is a consultant for ASC Therapeutics, BioMarin, Frontera, Metagenomi, Pfizer, Regeneron, and Spark Therapeutics. M.W.S.’s institution has received research funding from BioMarin, Freeline, Spark Therapeutics, and uniQure. The other authors have no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper addresses an immediate gap in knowledge about community reintegration of previously incarcerated older adults. It presents an exploratory case study of a community residential facility program in Ontario, Canada, focusing on the experiences and perspectives of older residents, staff members, and community stakeholders on the community reintegration of previously incarcerated older men. Findings provide insights into the aging-related reintegration issues such as the older men's ability to access health and medical services upon community reentry, the challenges and opportunities of the continuum of support (or lack thereof) to help ease the reintegration process, and stigma and other barriers the older men face as they attempt to access long-term care upon release from correctional institutions. Emergent questions for research, policy, and practice are highlighted and discussed to set an agenda for expanding the thread of inquiry into the community reintegration of previously incarcerated older adults. Future research calls for further investigation into the diversity of experiences (e.g., gender, race/ethnicity, geographical locale) to advance the field of study as it relates to aging and social policy.

Background: Establishing an effective continuum of care is a pivotal part of providing support for older populations. In contemporary practice; however, a subset of older adults experience delayed entry and/or are denied access to appropriate care. While previously incarcerated older adults often face barriers to accessing health care services to support community reintegration, there has been limited research on their transitions into long-term care. Exploring these transitions, we aim to highlight the challenges of securing long-term care services for previously incarcerated older adults and shed light on the contextual landscape that reinforces the inequitable care of marginalized older populations across the care continuum., Methods: We performed a case study of a Community Residential Facility (CRF) for previously incarcerated older adults which leverages best practices in transitional care interventions. Semi-structured interviews were conducted with CRF staff and community stakeholders to determine the challenges and barriers of this population when reintegrating back into the community. A secondary thematic analysis was conducted to specifically examine the challenges of accessing long-term care. A code manual representing the project themes (e.g., access to care, long-term care, inequitable experiences) was tested and revised, following an iterative collaborative qualitative analysis (ICQA) process., Results: The findings indicate that previously incarcerated older adults experience delayed access and/or are denied entry into long-term care due to stigma and a culture of risk that overshadow the admissions process. These circumstances combined with few available long-term care options and the prominence of complex populations already in long-term care contribute to the inequitable access barriers of previously incarcerated older adults seeking entry into long-term care., Conclusions: We emphasize the many strengths of utilizing transitional care interventions to support previously incarcerated older adults as they transition into long-term care including: 1) education & training, 2) advocacy, and 3) a shared responsibility of care. On the other hand, we underscore that more work is needed to redress the layered bureaucracy of long-term care admissions processes, the lack of long-term care options and the barriers imposed by restrictive long-term care eligibility criteria that sustain the inequitable care of marginalized older populations., (© 2023. The Author(s).)

Background: The National Hemophilia Foundation (NHF) conducted extensive all-stakeholder inherited bleeding disorder (BD) community consultations to inform a blueprint for future research. Sustaining and expanding the specialized and comprehensive Hemophilia Treatment Center care model, to better serve all people with inherited BDs (PWIBD), and increasing equitable access to optimal health emerged as top priorities., Research Design and Methods: NHF, with the American Thrombosis and Hemostasis Network (ATHN), convened multidisciplinary expert working groups (WG) to distill priority research initiatives from consultation findings. WG5 was charged with prioritizing health services research (HSR); diversity, equity, and inclusion (DEI); and implementation science (IS) research initiatives to advance community-identified priorities., Results: WG5 identified multiple priority research themes and initiatives essential to capitalizing on this potential. Formative studies using qualitative and mixed methods approaches should be conducted to characterize issues and meaningfully investigate interventions. Investment in HSR, DEI and IS education, training, and workforce development are vital., Conclusions: An enormous amount of work is required in the areas of HSR, DEI, and IS, which have received inadequate attention in inherited BDs. This research has great potential to evolve the experiences of PWIBD, deliver transformational community-based care, and advance health equity.

Genomic and gene-targeted therapies hold great promise in addressing the global issue of rare diseases. To achieve this promise, however, it is critical the twin goals of equity in access to testing and diagnosis, and equity in access to therapy be considered early in the life cycle of development and implementation. Rare disease researchers and clinicians must simultaneously recognize the life-altering potential of early diagnosis and administration of gene-targeted therapeutics while acknowledging that not everyone who experiences a rare disease and needs these therapies will be able to afford or access them. Achieving equity in the development of and access to gene-targeted therapies will not only require innovations in research, clinical, regulatory, and reimbursement frameworks, but will also necessitate increased attention to the ethical, legal, and social implications when establishing research paradigms and the translation of research results into novel interventions for rare genetic diseases. This article highlights and discusses the growing importance and recognition of health equity across the spectrum of rare disease research and care delivery., (© 2023 Wiley Periodicals LLC.)

Recent advancements in gene-targeted therapies have highlighted the critical role data sharing plays in successful translational drug development for people with rare diseases. To scale these efforts, we need to systematize these sharing principles, creating opportunities for more rapid, efficient, and scalable drug discovery/testing including long-term and transparent assessment of clinical safety and efficacy. A number of challenges will need to be addressed, including the logistical difficulties of studying rare diseases affecting individuals who may be scattered across the globe, scientific, technical, regulatory, and ethical complexities of data collection, and harmonization and integration across multiple platforms and contexts. The NCATS/NIH Gene-Targeted Therapies: Early Diagnosis and Equitable Delivery meeting series held during June 2021 included data sharing models that address these issues and framed discussions of areas that require improvement. This article describes these discussions and provides a series of considerations for future data sharing., (© 2023 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)