Approval rates for corneal donation and the origin of donor tissue for transplantation at a university-based tertiary referral center with corneal subspecialization hosting a LIONS Eye Bank

Background With the increasing demand for corneas, eye banks must optimize the tissue donation, collection, and selection process. This retrospective monocentric study analyzed the approval rates for corneal donation and the origin of and reasons for discarding donor corneas from 2010 to 2019. Methods Data included the number of deceased, approval or rejection by the family for corneal donation and contraindications. Corneal grafts were included from all deceased persons who were full-body and multi-organ donors at the Saarland University Medical Center (UKS) and from external institutions. Additional analyzed parameters included endothelial cell count (ECC), blood sample serology for infections, and conjunctival swab testing . Results A total of 1748 corneoscleral buttons were harvested from 10,265 deceased persons (17% with no contraindication) at the UKS between 2010 and 2019, with a consent rate of 23.3%. The number of keratoplasties increased from 136 in 2010 (15% of the deceased, total = 925) to 251 in 2019 (21%, total = 1214). Both the general and department-specific data showed similar percentages for corneal donation over the years, with intensive care and palliative units recently providing the most corneas. The increase in the number of corneas processed by the cornea bank over the years (368 in 2010 compared with 857 in 2019) was linked both to a better internal supply in 2010 (262, 71.2% of the total) compared with 2019 (519, 60.6%) and to an external supply by reinforcement of cooperation with external hospitals, including Luxembourg in 2010 (106, 28.8% of the total) compared with 2019 (338, 39.4%). A total of 195 of 377 corneas (52%) were discarded in 2009 compared with 260 out of 715 (36%) in 2019. The main reasons for discarding were low ECC (36% of discarded corneas in 2009; 11% in 2019), positive conjunctival swab (11% in 2009; 13% in 2019), and blood sample serology (6% in 2009 and in 2019). Conclusion Despite an increasing number of donors, the demand for corneas is still rising. Improved cooperation with internal departments and with external clinics has led to an increasing number of explanted corneas. The main reason for discarding corneas was low ECC, followed by a positive conjunctival swab for fungal or bacterial contamination and serology. Increased donation rates and continued improvements in collection and selection processes are necessary to cover the high demand for corneas.

Variations in Payment Allocation to Persons Living With Cognitive Impairment and Study Partners

There is a paucity of research focused on monetary incentives for recruiting dyads (participants with cognitive impairment and study partners) into research. Our objective was to evaluate if two different variations in allocating compensation among dyads changed consent rates in one clinical trial, Memories2. This trial is evaluating cognitive and functional outcomes of obstructive sleep apnea treatment in patients with amnestic mild cognitive impairment (aMCI). Prior to phone screening, participants were randomly assigned to one of two groups (1) $200 to participant with aMCI or (2) $100 to participant with aMCI and $100 to study partner at consent visit. Allocating all the payment to the participant with aMCI yielded a 2.6% consent rate, while splitting the payment yielded at 1.7% consent rate. We will also discuss how demographic factors affected consent decision by group. This study provides insight into novel strategies that may enhance enrollment of dyads into clinical trials.

Comparing an optimised physiotherapy treatment package with usual physiotherapy care for people with Tennis Elbow – protocol for the OPTimisE pilot and feasibility randomised controlled trial.

BackgroundPhysiotherapy is recommended for people with Tennis Elbow, but whilst a wide array of treatments is available, the optimal approach remains uncertain. We have therefore recently developed an optimised physiotherapy treatment package for Tennis Elbow based on a synthesis of the evidence, patient input, and clinical consensus. It consists of detailed advice and education, a structured progressive exercise programme and provision of a counter-force elbow brace. Here we report the protocol for our multi-centre pilot and feasibility randomised controlled trial (RCT) designed to a) examine the feasibility of our optimised physiotherapy treatment package, and b) to pilot trial processes for a future fully-powered RCT to test clinical and cost-effectiveness compared with usual physiotherapy treatment.MethodsA multi-centre pilot and feasibility RCT will be conducted across three sites in England, recruiting up to 50 patients (or for a maximum of 12 months). Participants with Tennis Elbow, identified from physiotherapy clinic waiting lists and general practice surgeries, will be randomly allocated to receive the optimised physiotherapy treatment package or usual physiotherapy care. Analysis will focus on feasibility measures including; consent rate, intervention fidelity, follow-up rate, and outcome completion rate. A nested qualitative study will explore the acceptability of the study processes and patient and physiotherapist experiences of the new optimised intervention.DiscussionThis study will determine the feasibility of a new optimised physiotherapy treatment package for people with Tennis Elbow and pilot the processes for a future fully-powered RCT. In the longer term, this treatment package may improve pain and quality of life outcomes for people with Tennis Elbow and help to guide a more clinically and economically efficient treatment pathway design.Trial RegistrationRegistered with the ISRCTN database 19/7/2021. https://www.isrctn.com/ISRCTN64444585

Implementing Digital Technology to Transitioning a Clinical Trial to a Registry – TAILOR-PCI Digital Study: Methods/Study Design (Preprint)

BACKGROUND TAILOR-PCI was the largest cardiovascular genotype-based randomized clinical trial (RCT) investigating whether CYP2C19 genotype-guided selection of oral P2Y12 inhibitor therapy improved ischemic outcomes after percutaneous coronary intervention (PCI). The TAILOR-PCI Digital Registry was a novel proof-of-concept study that evaluated the feasibility of extending the main RCT follow-up period using a remote digital platform. OBJECTIVE To describe patients onboarding, engagement and results of a digital registry after enrollment in a RCT. METHODS In this intervention study, previously enrolled TAILOR-PCI patients in the United States and Canada within 24 months of randomization were invited by letters containing a URL to the TAILOR-PCI Digital Registry website (http://tailorpci.eurekaplatform.org), instructing them to download the study app. Patients previously enrolled in the TAILOR-PCI study, with a smartphone, were eligible to join the Digital Registry. Those who did not respond to the letter were contacted by phone to survey reasons for non-participation and were invited again to join the study. A direct-to-patient digital research platform (the Eureka Research Platform) was used to onboard, consent and enrol patients in the Digital Registry. Patients were asked to complete health-related surveys and provide follow-up data digitally. Consent rate to the Digital Registry, duration of participation in the Digital Registry and monthly activity completion rate. The hypothesis being tested was formulated before data collection began. RESULTS After the parent trial was completed, letters were mailed to 907 eligible patients (representing 19% of total enrolled in the RCT) across 24 sites, who were within 15.6 ± 5.2 months after randomization leading to 290 unique individuals visits to the Digital Registry website. Among those invited, 110 patients (12%) consented: 45 (41%) after the letter, 37 (34%) after the 1st phone call and 28 (25%) after a 2nd call. Of the 862 who didn’t consent after the letter, 453 patients (53%) did not respond to repeated phone calls and among the 409 patients who responded, 171 (41%) declined participation stating lack of time, 128 (31%), due to lack of smartphone and 47 (11%) due to difficulty understanding what was expected of them in the study. Patients who consented were older, had less diabetes or tobacco use; a greater proportion had bachelor's degrees or higher and were more computer literate than those who did not consent. The average completion rate of the 920 available monthly electronic visits was 64.9±7.6% without a decrease in this rate throughout the study duration. There were no differences between randomization arms in any patient reported outcomes using the digital platform. CONCLUSIONS Extended follow-up after enrollment in a RCT using a digital registry is technically feasible but was limited due to inability to contact most eligible patients, lack of time or access to a smartphone. Among those enrolled, most patients completed required electronic visits. Enhanced recruitment methods, such as introduction of the digital study at the time of RCT consent, provision of smartphone and robust study support for onboarding, should be explored further. CLINICALTRIAL TAILOR-PCI (Clinicaltrials.gov: NCT01742117)

Systematic tissue collection during clinical breast biopsy is feasible, safe and enables high-content translational analyses

Systematic collection of fresh tissues for research at the time of diagnostic image-guided breast biopsy has the potential to fuel a wide variety of innovative studies. Here we report the initial experience, including safety, feasibility, and laboratory proof-of-principle, with the collection and analysis of research specimens obtained via breast core needle biopsy immediately following routine clinical biopsy at a single institution over a 14-month period. Patients underwent one or two additional core biopsies following collection of all necessary clinical specimens. In total, 395 patients were approached and 270 consented to the research study, yielding a 68.4% consent rate. Among consenting patients, 238 lesions were biopsied for research, resulting in 446 research specimens collected. No immediate complications were observed. Representative research core specimens showed high diagnostic concordance with clinical core biopsies. Flow cytometry demonstrated consistent recovery of hundreds to thousands of viable cells per research core. Among a group of HER2 + tumor research specimens, HER2 assessment by flow cytometry correlated highly with immunohistochemistry (IHC) staining, and in addition revealed extensive inter- and intra-tumoral variation in HER2 levels of potential clinical relevance. Suitability for single-cell transcriptomic analysis was demonstrated for a triple-negative tumor core biopsy, revealing substantial cellular diversity in the tumor immune microenvironment, including a prognostically relevant T cell subpopulation. Thus, collection of fresh tissues for research purposes at the time of diagnostic breast biopsy is safe, feasible and efficient, and may provide a high-yield mechanism to generate a rich tissue repository for a wide variety of cross-disciplinary research.

“This Graft-vs.-Host Disease Determines My Life. That's It.”—A Qualitative Analysis of the Experiences and Needs of Allogenic Hematopoietic Stem Cells Transplantation Survivors in Germany

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative treatment modality for many patients affected by hematologic malignancies. However, it can cause debilitating long-term effects. Understanding the impact of alloHSCT on all aspects of the patients' life is required for optimal survivorship management.Aim: To explore in-depth HSCT-survivors' experiences and needs post-transplant. Partners were included to provide further information on survivors' needs and how care could be improved in this area.Methods: We conducted semi-structured face-to-face and phone interviews with alloHSCT-survivors and their partners referred to a survivorship clinic in Germany. Theoretical sampling was used to recruit participants. Data were analyzed using framework analysis.Results: Thirty-two survivors (consent rate: 100%, response rate: 100%) and eighteen partners (consent rate: 84%, response rate: 72%) participated. Survivors were aged between 25 and 68 years (Median: 48, IQR: 25.3) and partners were aged between 26 and 64 years (Median: 54, IQR: 16, SD: 12.8). The themes emerging from the data involved survivors' needs included (i) the diversity of long-term treatment side-effects; and (ii) time post discharge as a dynamic process with individual peaks of burden. Survivors and their partners also suggested strategies for mitigating these unmet needs, i.e., (iii) transparent communication and patient empowerment; and (iv) improvement in continuity of care system and help with claiming social benefits as cornerstones of optimal survivorship care.Conclusion: To our knowledge, this is one of the first qualitative studies focused on the views of German alloHSCT-survivors on the long-term effects of alloHSCT and the first study integrating the view of their partners. Healthcare providers could better support survivors with managing their symptoms and adhering to their prescribed care by ensuring comprehensive, transparent communication that helps increase survivors' understanding and involvement in their care. Further efforts should be made to provide patient-centered, continuous survivorship care that involves additional support with navigating the healthcare and social service system. Intervention studies are required to test the effectiveness of the suggested strategies.

Telephone-based depression self-management in Hispanic adults with epilepsy: a pilot randomized controlled trial

Depression is associated with adverse outcomes in epilepsy but is undertreated in this population. Project UPLIFT, a telephone-based depression self-management program, was developed for adults with epilepsy and has been shown to reduce depressive symptoms in English-speaking patients. There remains an unmet need for accessible mental health programs for Hispanic adults with epilepsy. The purpose of this study was to evaluate the feasibility, acceptability, and effects on depressive symptoms of a culturally adapted version of UPLIFT for the Hispanic community. Hispanic patients with elevated depressive symptoms (n = 72) were enrolled from epilepsy clinics in New York City and randomized to UPLIFT or usual care. UPLIFT was delivered in English or Spanish to small groups in eight weekly telephone sessions. Feasibility was assessed by recruitment, retention, and adherence rates and acceptability was assessed by self-reported satisfaction with the intervention. Depressive symptoms (PHQ-9 scores) were compared between study arms over 12 months. The mean age was 43.3±11.3, 71% of participants were female and 67% were primary Spanish speakers. Recruitment (76% consent rate) and retention rates (86–93%) were high. UPLIFT participants completed a median of six out of eight sessions and satisfaction ratings were high, but rates of long-term practice were low. Rates of clinically significant depressive symptoms (PHQ-9 ≥5) were lower in UPLIFT versus usual care throughout follow-up (63% vs. 72%, 8 weeks; 40% vs. 70%, 6 months; 47% vs. 70%, 12 months). Multivariable-adjusted regressions demonstrated statistically significant differences at 6 months (OR = 0.24, 95% CI, 0.06–0.93), which were slightly reduced at 12 months (OR = 0.30, 95% CI, 0.08–1.16). Results suggest that UPLIFT is feasible and acceptable among Hispanic adults with epilepsy and demonstrate promising effects on depressive symptoms. Larger trials in geographically diverse samples are warranted.

Clinical Characteristics and Outcomes of Critically Ill Mechanically Ventilated Patients Receiving Adjunctive Ketamine for Sedation: an Investigator-Driven, Open-Label, Randomized, Controlled Trial

BackgroundKetamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are lacking on patient-centered outcomes. We aimed to compare the clinical characteristics and outcomes of mechanically ventilated adult ICU patients receiving ketamine as an adjunct analgosedative with those receiving standard of care (SOC) alone. We also described the feasibility during COVID-19 pandemic.MethodsIn this randomized, open-label trial either ketamine or SOC, in a 1:1 ratio, was administered to patients who were intubated within 24 hours (medical, surgical, or transplant/oncology ICUs), expected to require mechanical ventilation (MV) for the next calendar day, and had the institutional pain and sedation protocol initiated. Ketamine infusion was 2 μg/kg/min on day 1 and 1 μg/kg/min on day 2. The primary outcome was the 28-day MV duration and ventilator-free days as co-primary outcome. Cox-proportional regression analysis was used to assess factors associated with probability for weaning off MV.ResultsA total of 83 patients (43 in SOC and 40 in ketamine) were included. Demographics were balanced between the groups. The median duration of MV was not significantly different between the groups [median (interquartile range): 7 (3-9.25) for ketamine and 5 (2-8) for SOC, p= 0.15]. The median ventilation-free days was 19 days (IQR 0-24.75) in the ketamine and 19 days (IQR 0-24) in the SOC (p=0.70). Surgical and transplant/oncology ICU patients had a higher probability of weaning off MV than those in medical ICU [hazard ratio (95% confidence interval): 2.09 (1.06–4.14) for surgical ICU, 2.11 (1.02–4.35) for transplant/oncology ICU]. More patient was at goal RASS in ketamine compared to SOC. The sedatives and vasopressors cumulative doses were similar between the two arms at 48 hours. We found no difference in 28-day mortality rate, ICU and hospital length of stay, and hemodynamic changes. The consent rate was adequate and the protocol adherence rate was 97.5%.ConclusionsKetamine as an adjunct agent for sedation did not decrease the duration of MV and appeared to be safe, feasible, and effective in subgroups of ICU patients. No effect was noted in sedative and pressors requirements, or on hemodynamics.Trial registrationClinicalTrials.gov: NCT04075006 and current-controlled trials: ISRCTN14730035

School-level Factors and Consent Form Return Rate in a School-based Vision Program

Objective: School-based vision programs provide care directly in schools. Parental consent is typically required for student participation. In this paper, we examine school-level factors associated with consent form return. Methods: We included 123 schools served by a vision program in Baltimore, Maryland between the 2016-17 and 2018-19 school years. Multiple linear regression modeling was used to examine the associations between consent return rate and school type (elementary, elementary/middle or middle school), school size, student attendance, student mobility, percent of students in special education, poverty (percent eligible for free and reduced-price lunch), teacher qualifications, parent response rate to annual school climate survey, vision screening failure rate, and year of vision program participation (cohort). Results: The final model explained 26.2% of variability in consent return rate. Overall consent return rate was 57.8% (range 9.4%-100%). School size (β = -2.419, p < .01) and cohort (βCohort2 = 11.988, p < .01) were significantly associated with consent rate. Whereas poverty (β = 0.225, p < .10) and mobility (β = -0.647, p < .10) were relevant, they did not reach statistical significance. Conclusions: School-level factors are significantly associated with consent form return rates. School-based vision programs should consider additional measures to increase consent form return, especially in larger schools and schools with high rates of student mobility.