Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study.

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676.

Centre of pressure golf swing movement strategies are better defined using a continuous approach than by segregated styles.

The relationships between movement style and golf performance have been well researched, but the premise of segregated movement styles has not been fully examined. The purpose of this investigation was to examine the postulation that centre of pressure data are not best described by segregated styles but instead by a continuum and to determine relationships between centre of pressure, handicap and clubhead speed using a continuous approach. Centre of pressure paths of driver and 5-iron shots from 104 amateur golfers were analysed using discrete and continuous methods. Discrete methods used different cluster evaluation criteria which result in two-cluster and twenty-cluster solutions being considered "optimum". The two-cluster solution showed the characteristics of "front-foot" and "reverse" centre of pressure styles. However, a continuous principal component analysis method revealed that the clusters were not well separated and provided support for a multidimensional continuum. The principal components had a high correlation with handicap and clubhead speed. Lower handicap and higher swing speed golfers tended to display a centre of pressure with a "front-foot" style and a fast transition towards the front foot at the start of the downswing. A continuous characterisation of centre of pressure styles has more utility than the segregated styles previously described.

Inequity in Telemedicine Use Among Patients with Cancer in the Deep South During the COVID-19 Pandemic.

BACKGROUND: Telemedicine use has increased significantly during the COVID-19 pandemic. It remains unclear if its rapid growth exacerbates disparities in healthcare access. We aimed to characterize telemedicine use among a large oncology population in the Deep South during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective cohort study was performed at the only National Cancer Institute designated-cancer center in Alabama March 2020 to December 2020. With a diverse (26.5% Black, 61% rural) population, this southeastern demographic uniquely reflects historically vulnerable populations. All non-procedural visits at the cancer center from March to December 2020 were included in this study excluding those with a department that had fewer than 100 visits during this time period. Patient and clinic level characteristics were analyzed using t-test and Chi-square to compare characteristics between visit types (in-person versus telemedicine, and video versus audio within telemedicine). Generalized estimating equations were used to identify independent factors associated with telemedicine use and type of telemedicine use. RESULTS: There were 50 519 visits and most were in-person (81.3%). Among telemedicine visits, most were phone based (58.3%). Black race and male sex predicted in-person visits. Telemedicine visits were less likely to have video among patients who were Black, older, male, publicly insured, and from lower income areas. CONCLUSIONS: Telemedicine use, specifically with video, is significantly lower among historically vulnerable populations. Understanding barriers to telemedicine use and preferred modalities of communication among different populations will help inform insurance reimbursement and interventions at different socioecological levels to ensure the continued evolution of telemedicine is equitable.

Expanding access to substance use services and mental health care for people with HIV in Alabama, a technology readiness assessment using a mixed methods approach.

BACKGROUND: Alabama is one of seven priority states for the National Ending the HIV Epidemic Initiative due to a large rural burden of disease. Mental health (MH) and substance use disorders (SUD) represent obstacles to HIV care in rural areas lacking Medicaid expansion and infrastructure. Evidence-informed technologies, such as telehealth, may enhance SUD and MH services but remain understudied in rural regions. METHODS: We conducted a readiness assessment using a mixed methods approach to explore opportunities for enhanced SUD and MH screening using electronic patient reported outcomes (ePROs) and telehealth at five Ryan White HIV/AIDS Program-funded clinics in AL. Clinic providers and staff from each site (N = 16) completed the Organizational Readiness to Implement Change (ORIC) assessment and interviews regarding existing services and readiness to change. People with HIV from each site (PLH, N = 18) completed surveys on the acceptability and accessibility of technology for healthcare. RESULTS: Surveys and interviews revealed that all clinics screen for depression annually by use of the Patient Health Questionnaire-9 (PHQ9). SUD screening is less frequent and unstandardized. Telehealth is available at all sites, with three of the five sites beginning services due to the COVID-19 pandemic; however, telehealth for MH and SUD services is not standardized across sites. Results demonstrate an overall readiness to adopt standardized screenings and expand telehealth services beyond HIV services at clinics. There were several concerns including Wi-Fi access, staff capacity, and patients' technological literacy. A sample of 18 people with HIV (PWH), ages 18 to 65 years, participated in surveys; all demonstrated adequate technology literacy. A majority had accessed telehealth and were not concerned about it being too complicated or limiting communication. There were some concerns around lack of in-person interaction and lack of a physical exam and high-quality care with telehealth. CONCLUSION: This study of PWH and the clinics that serve them reveals opportunities to expand SUD and MH services in rural regions using technology. Areas for improvement include implementing routine SUD screening, expanding telehealth while maintaining opportunities for in-person interaction, and using standardized ePROs that are completed by patients, in order to minimize stigma and bias.

KDOQI US Commentary on the 2020 ISPD Practice Recommendations for Prescribing High-Quality Goal-Directed Peritoneal Dialysis.

The recently published 2020 International Society for Peritoneal Dialysis (ISPD) practice recommendations regarding prescription of high-quality goal-directed peritoneal dialysis differ fundamentally from previous guidelines that focused on "adequacy" of dialysis. The new ISPD publication emphasizes the need for a person-centered approach with shared decision making between the individual performing peritoneal dialysis and the clinical care team while taking a broader view of the various issues faced by that individual. Cognizant of the lack of strong evidence for the recommendations made, they are labeled as "practice points" rather than being graded numerically. This commentary presents the views of a work group convened by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) to assess these recommendations and assist clinical providers in the United States in interpreting and implementing them. This will require changes to the current clinical paradigm, including greater resource allocation to allow for enhanced services that provide a more holistic and person-centered assessment of the quality of dialysis delivered.

Telehealth for Home Dialysis in COVID-19 and Beyond: A Perspective From the American Society of Nephrology COVID-19 Home Dialysis Subcommittee.

The coronavirus disease 2019 (COVID-19) pandemic, technological advancements, regulatory waivers, and user acceptance have converged to boost telehealth activities. Due to the state of emergency, regulatory waivers in the United States have made it possible for providers to deliver and bill for services across state lines for new and established patients through Health Insurance Portability and Accountability Act (HIPAA)- and non-HIPAA-compliant platforms with home as the originating site and without geographic restrictions. Platforms have been developed or purchased to perform videoconferencing, and interdisciplinary dialysis teams have adapted to perform virtual visits. Telehealth experiences and challenges encountered by dialysis providers, clinicians, nurses, and patients have exposed health care disparities in areas such as access to care, bandwidth connectivity, availability of devices to perform telehealth, and socioeconomic and language barriers. Future directions in telehealth use, quality measures, and research in telehealth use need to be explored. Telehealth during the public health emergency has changed the practice of health care, with the post-COVID-19 world unlikely to resemble the prior era. The future impact of telehealth in patient care in the United States remains to be seen, especially in the context of the Advancing American Kidney Health Initiative.

Can you hear me now?: Improving palliative care access through telehealth.

Telehealth has been increasingly used to expand healthcare access over the last two decades. However, this had not been the case for palliative care (PC), because telehealth was considered nontraditional and impractical due to the sensitive nature of conversations and a "high touch" philosophy. Motivated by limited PC access to rural and underserved populations and positive PC telehealth studies, clinical PC telehealth models have been developing. However, nearly overnight, the COVID-19 pandemic accelerated the use and uptake of telehealth across health care and especially in PC. As a result, clinicians, administrators, and others agree that telehealth is "here to stay," and will likely maintain widespread use and refinement beyond rural areas. The purpose of this review is to describe exemplar PC telehealth programs in research and clinical practice, including pros and cons, lessons learned, and future directions for the ongoing development and expansion of PC via telehealth across diseases and the lifespan.

Diagnosis in a snap: a pilot study using Snapchat in radiologic didactics.

PURPOSE: To evaluate Snapchat, an image-based social media platform, as a tool for emergency radiologic didactics comparing image interpretation on mobile devices with conventional analysis on a classroom screen. MATERIALS AND METHODS: Seven radiology residents (4 juniors, 3 seniors;4 males, 3 females; 28.4 years old, ± 1.7 years) were shown 5 emergent radiologic cases using Snapchat and 5 cases of similar content and duration on a classroom projector over 4 weeks. All images depicted diagnoses requiring immediate communication to ordering physicians. Performance was scored 0-2 (0 = complete miss, 1 = major finding, but missed the diagnosis, 2 = correct diagnosis) by two attending radiologists in consensus. RESULTS: All residents performed better on Snapchat each week. In weeks 1-4, juniors scored 21/40 (52.5%), 23/40 (57.5%), 19/40 (47.5%), and 18/40 (45%) points using Snapchat compared with 13/40 (32.5%), 23/40 (57.5%), 14/40 (35%), and 13/40 (32.5%), respectively, each week by projector, while seniors scored 19/30 (63.3%), 21/30 (70%), 27/30 (90%), and 21/30 (70%) on Snapchat versus 16/30 (53.3%), 19/30 (63.3%), 20/30 (66.7%), and 20/30 (66.7%) on projector. Four-week totals showed juniors scoring 81/160 (50.6%) on Snapchat and 63/160 (39.4%) by projector compared with seniors scoring 88/120 (73.3%) and 75/120 (62.5%), respectively. Performance on Snapchat was statistically, significantly better than via projector during weeks 1 and 3 (p values 0.0019 and 0.0031). CONCLUSION: Radiology residents interpreting emergency cases via Snapchat showed higher accuracy compared with using a traditional classroom screen. This pilot study suggests that Snapchat may have a role in the digital radiologic classroom's evolution.

Overcoming Barriers for Uptake and Continued Use of Home Dialysis: An NKF-KDOQI Conference Report.

Home dialysis modalities are used in a minority of patients with kidney failure in the United States. During the 2018 National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) Home Dialysis Conference, numerous ideas were suggested to help minimize barriers for the uptake and retention of home dialysis therapies. First, educational tools are needed to increase knowledge about home dialysis modalities (eg, continuous ambulatory peritoneal dialysis, continuous cycling peritoneal dialysis, and home hemodialysis). Implementation of a hub and spoke model, pairing smaller and/or newer home dialysis programs with larger more sophisticated programs that offer education and mentoring, may help dialysis programs to grow and prosper. This pairing can be facilitated by traditional conferences and newer modalities such as telemedicine and training applications. Peer support to patients, such as that offered through the NKF Peers Program, and support and respite to care partners can have beneficial effects toward both increasing the number of patients who choose home dialysis as a modality and improving retention in home dialysis programs. Anticipating and understanding both patient and care partner burden is important for the development and implementation of patient- and care partner-centered support programs that can be deployed before a patient ceases home therapy. Finally, aligning Medicare reimbursement to support appropriate increased home dialysis uptake to prioritize both transplantation and home dialysis as the first-line treatments for kidney failure.

Exploring Barriers and Potential Solutions in Home Dialysis: An NKF-KDOQI Conference Outcomes Report.

Home dialysis therapy, including home hemodialysis and peritoneal dialysis, is underused as a modality for the treatment of chronic kidney failure. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative sponsored a home dialysis conference in late 2017 that was designed to identify the barriers to starting and maintaining patients on home dialysis therapy. Clinical, operational, policy, and societal barriers were identified that need to be overcome to ensure that dialysis patients have the freedom to choose their treatment modality. Education of patients and patient partners, as well as health care providers, about home dialysis therapy, if offered at all, is often provided in a cursory manner. Lack of exposure to home dialysis therapies perpetuates a lack of familiarity and thus a hesitancy to refer patients to home dialysis therapies. Patient and care partner support, both psychosocial and financial, is also critical to minimize the risk for burnout leading to dropout from a home dialysis modality. Thus, the facilitation of home dialysis therapy will require a systematic change in chronic kidney disease education and the approach to dialysis therapy initiation, the creation of additional incentives for performing home dialysis, and breakthroughs to simplify the performance of home dialysis modalities. The home dialysis work group plans to develop strategies to overcome these barriers to home dialysis therapy, which will be presented at a follow-up home dialysis conference.

Measuring what matters in isometric multi-joint rate of force development.

This study aimed to evaluate responsiveness (ability to detect change) of isometric force-time measures to neuromuscular fatigue in resistance-trained participants using two differing protocols that modified both the instructions provided to participants and the duration of the test. Both protocols were completed at two knee joint angles in the isometric squat test. Ten participants volunteered to take part in this study (age: 27.0 ± 4.5 years, strength training experience: 7.7 ± 2.6 years). Isometric peak force (ISqTpeak) and isometric explosive force (ISqTexp) test protocols were assessed at two joint angles (knee angle 100° and 125°) pre-high intensity strength training, immediately post strength training, 24-h post, 48-h post and analysed for peak and RFD performance. Participants completed eight sets of three repetitions of the back-squat exercise as the high-intensity strength training. Results showed the highest standardised response means (SRM) detected was peak force using the ISqTpeak 100, SRM -1.97 compared to an SRM of -1.31 for RFD 200 ms in the ISqTexp 125. Peak force was the most responsive variable using the ISqTpeak protocol, whereas the ISqTexp protocol was most responsive for RFD measures. Therefore, ISqTpeak and ISqTexp test protocols should not be used interchangeably to evaluate RFD variables.

Multi-joint rate of force development testing protocol affects reliability and the smallest detectible difference.

Isometric tests have been used to assess rate of force development (RFD), however variation in testing methodologies are known to affect performance outcomes. The aim of this study was to assess the RFD in the isometric squat (ISqT) using two test protocols and two testing angles. Eleven participants (age: 26.8 ± 4.5 years, strength training experience: 7.1 ± 3.03 years) completed test and retest sessions one week apart, whereby two test protocols with respect to duration and instructions were compared. Isometric peak force (ISqTpeak) and isometric explosive force (ISqTexp) tests were assessed at two joint angles (knee flexion angle 100° and 125°). Force-time traces were sampled and subsequently analysed for RFD measures. Average and instantaneous RFD variables did not meet reliability minimum criteria in ISqTpeak at 100° or 125°. The ISqTexp test at 100° met reliability criteria in the RFD 0-200 and 0-250ms variables. The ISqTexp test at 125° met reliability criteria in the RFD 0-150, 0-200 and 0-250ms variables. Force-time characteristics were optimized at the higher knee joint angle. Average and instantaneous RFD measures obtained using a traditional peak force test do not meet basic reliability criteria. Researchers assessing multi-joint RFD should employ the explosive RFD test protocol as opposed to the traditional isometric peak force protocol.

Fabry disease revisited: Management and treatment recommendations for adult patients.

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the "classic" phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. However, much of the current literature reports outcomes after late initiation of ERT, once substantial organ damage has already occurred. Updated monitoring and treatment guidelines for pediatric patients with Fabry disease have recently been published. Expert physician panels were convened to develop updated, specific guidelines for adult patients. Management of adult patients depends on 1) a personalized approach to care, reflecting the natural history of the specific disease phenotype; 2) comprehensive evaluation of disease involvement prior to ERT initiation; 3) early ERT initiation; 4) thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients; 5) use of adjuvant treatments for specific disease manifestations; and 6) management by an experienced multidisciplinary team.

Clinical parameters, LysoGb3, podocyturia, and kidney biopsy in children with Fabry disease: is a correlation possible?

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase enzyme deficiency. We present clinical, biochemical, and histologic findings in children with classical phenotypic presentation of Fabry disease. METHODS: A retrospective analysis was performed using charts from 14 children with confirmed diagnosis. Clinical parameters were evaluated. Globotriaosylsphingosine -lysoGb3- detection in plasma, podocyturia, and kidney biopsy were carried out in all cases. RESULTS: All patients except one demonstrated at least one symptom of Fabry disease. LysoGb3 levels were above the normal range in all patients. Podocyturia was documented in all patients. Kidney biopsy revealed glomerular, interstitial, vascular, and tubular changes on light microscopy in nearly all patients. Electron microscopy showed podocyte inclusions in all patients. CONCLUSIONS: No difference in symptomatology was discernible between boys and girls. Podocyturia was detectable in children serving as a possible early marker of kidney injury. LysoGb3 was elevated in all cases, emphasizing the importance for diagnosis especially in female patients with normal αGal A activity. A possible association between lysoGb3 and symptom severity and histological involvement in kidney biopsy should be assessed in prospective studies with enough statistical power to determine if lysoGb3 can be used to predict nephropathy in children with Fabry disease.

The relationship between the golf swing plane and ball impact characteristics using trajectory ellipse fitting.

The trajectory of the clubhead close to ball impact during the golf swing has previously been shown to be planar. However, the relationship between the plane orientation and the orientation characteristics of the clubhead at ball impact has yet to be defined. Fifty-two male golfers (27 high skilled, 25 intermediate skilled) hit 40 drives each in an indoor biomechanics laboratory. This study successfully fitted the trajectory of the clubhead near impact to an ellipse for each swing for players of different skill levels to help better explain this relationship. Additionally, the eccentricities of the ellipses were investigated for links to skill level. The trajectory of the clubhead was found to fit to an ellipse with RMSE of 1.2 mm. The eccentricity of the ellipse was found to be greater in the high-skilled golfers. The club path and angle of attack generated from the ellipse fitted clubhead trajectory were found to have a normalised bias-corrected RMSE of 2% and 3%, respectively. A set of "rule of thumb" values for the relationship between the club path, angle of attack and delivery plane angle was generated for use by coaches.

Familiarization, validity and smallest detectable difference of the isometric squat test in evaluating maximal strength.

Isometric multi-joint tests are considered reliable and have strong relationships with 1RM performance. However, limited evidence is available for the isometric squat in terms of effects of familiarization and reliability. This study aimed to assess, the effect of familiarization, stability reliability, determine the smallest detectible difference, and the correlation of the isometric squat test with 1RM squat performance. Thirty-six strength-trained participants volunteered to take part in this study. Following three familiarization sessions, test-retest reliability was evaluated with a 48-hour window between each time point. Isometric squat peak, net and relative force were assessed. Results showed three familiarizations were required, isometric squat had a high level of stability reliability and smallest detectible difference of 11% for peak and relative force. Isometric strength at a knee angle of ninety degrees had a strong significant relationship with 1RM squat performance. In conclusion, the isometric squat is a valid test to assess multi-joint strength and can discriminate between strong and weak 1RM squat performance. Changes greater than 11% in peak and relative isometric squat performance should be considered as meaningful in participants who are familiar with the test.

Thromboinflammatory response and predictors of outcomes in patients undergoing transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) has been increasingly used to treat patients with symptomatic aortic stenosis. Despite improvements in valve deployment, patients that have undergone TAVR are at high risk for major adverse events following the procedure. Blood cell numbers, platelet function, and biomarkers of systemic inflammation were analyzed in 58 patients undergoing TAVR with the Edward's SAPIEN valve. Following valve deployment, platelet count and agonist-induced platelet activity declined and plasma markers of systemic inflammation (interleukin-6 and S100A8/A9) increased. Baseline platelet activity prior to TAVR correlated with perioperative changes plasma interleukin-6 levels. Moreover, perioperative changes in plasma inflammatory markers predicted the decline in platelet count in the days following the TAVR procedure. Additionally, a significant effect of gender on platelet count following TAVR and was observed. Finally, post-procedural mortality was associated with sustained thrombocytopenia after TAVR. Our findings suggest that TAVR elicits a thromboinflammatory state that may contribute to post-procedural thrombocytopenia. Importantly, our results add to the growing body of literature that suggests the thromboinflammatory changes that occur early after TAVR may predict long-term outcomes.