Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases: Third of Three Sets of Expanded Proceedings from the 2020 ISCTM Autumn Conference on Pediatric Drug Development

This article expands on a session, titled "Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs, including implications for rare/orphan diseases. The speakers have written summaries of their talks. The session's lead Chair was Dr. Joan Busner, who wrote introductory and closing comments. Dr. Simon Day, regulatory consultant, outlined some of the past mistakes that have plagued trials that did not consult with patient groups in the early design phase. Dr. Atul Mahableshwarkar provided an industry perspective of a recent trial that benefited from the inclusion of patient input. Drs. Lucas Kempf and Maria Sheean provided regulatory input from the perspectives of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Dr. Judith Dunn outlined a novel approach for assessing and rank ordering patient and clinician clinical meaningfulness and the disconnect that may occur. Dr. Busner provided closing comments, tied together the presented issues, and provided a synopsis of the lively discussion that followed the session. In addition to the speakers above, the discussion included two representatives from patient advocacy groups, as well as an additional speaker who described the challenges of conducting a pediatric trial in the US and European Union (EU), given the often competing regulatory requirements. This article should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and rare diseases and seek to ensure a patient-centric approach.Copyright © 2023, Matrix Medical Communications. All rights reserved.

Unobtrusive In-Home Respiration Monitoring Using a Toilet Seat

Non-invasive monitoring of pulmonary health could revolutionize the care of health conditions ranging from COVID-19 to asthma to heart failure, but current technologies face challenges that limit their feasibility and adoption. Here, we introduce a novel approach to monitor respiration by measuring changes in impedance from the back of the thigh. The integration of electrodes into a toilet seat ensures patient compliance with unobtrusive daily respiration monitoring benefitting from repeatable electrode placement on the skin. In this work, the feasibility of the thigh and the sensitivity of impedance to respiration have been investigated empirically by comparing thorax and thigh-thigh bioimpedance measurements to spirometer measurements, and computationally, using finite element modeling. Empirical results show a measurable peak-peak impedance (0.022 ohm to 0.290 ohm for normal breathing across 8 subjects) with respiration across thigh-thigh and a high correlation (0.85) between lung tidal volume and impedance change due to respiration. Thigh-thigh bioimpedance measurements were found to be able to distinguish between shallow, normal, and deep breathing. Further, day-to-day variability in the relationship between impedance and tidal volume was investigated. The results suggest that the novel approach can be used to detect respiration rate and tidal volume and could provide valuable insight into disease state for conditions ranging from COVID-19 to heart failure. © 2022 IEEE.

SYMPTOM STATUS AND POSTAL KIT RETURN RATES OF INDIVIDUALS ACCESSING AN ONLINE SEXUALLY TRANSMITTED INFECTION (STI) TESTING SERVICE

Background Online sexual health services (e-services) are being increasingly used for STI testing. Reduced sexual health clinic capacity due to the Covid-19 pandemic prompted our regional e-service to widen eligibility and enable individuals with mild symptoms to access our service. Prior to placing a kit order, information was shown to all symptomatic service users, advising them of the benefits of attending a sexual health clinic and/or to attend a clinic if symptoms persist/worsen. Method A retrospective analysis was performed of service users that ordered a testing kit between March 2020, and December 2021. Kit return rates were compared according to symptom status. Results Of 888,619 kit orders 163,023 (18.3%) came from symptomatic users. The most common symptom reported was vaginal discharge (41.1%), followed by dysuria/frequency (18.4%) and itching (13.8%). The kit return rate among asymptomatic service users was significantly higher (79.3%) compared to symptomatic users (74.3%) (X2 6.04. p =0.01401). The highest return rates were seen among individuals with itching (75.8%), dysuria/frequency (75.7%) and vaginal discharge (74.6%). The lowest return rate was seen by individuals with genital lumps (71.2%). Discussion Significantly fewer kits were returned by symptomatic e-service users compared to asymptomatics. It is plausible the e-service advisory information deterred some users from returning kits, encouraging them to instead test at a clinic. However, many users opted to complete testing online or perhaps did so because of difficulty accessing a sexual health clinic. Further work is needed to explore the preferred modality of testing provider and the suitability of online services for symptomatic individuals.

DOMESTIC ABUSE AND/OR VIOLENCE (DA/V) REPORTING BY SERVICE USERS (SUS) OF A REGIONAL ONLINE SEXUALLY TRANSMITTED INFECTION (STI) TESTING SERVICE (E-SERVICE), DURING THE COVID-19 PANDEMIC

Introduction DA/V increased over the pandemic Our e-service widened access during the crisis and introduced three questions to adult SUs enquiring about DA/V. An analysis of SUs triggering these questions is provided. Method E-notes review of SUs who triggered question(s) about current DA/DV, whilst ordering a kit between 17.8.21- 28.2.22. SUs that trigger are automatically offered access to supportive online information. The e-service team don't directly contact these SUs unless there's another reason (e.g. relaying positive STI results). If safe to do so, the triggers are discussed during these calls and further support/counselling offered. Results 3846/231460(1.7%) SU triggered DA/V question(s) between 17.8.21-28.2.22. The first 202 SU e-notes were reviewed: median age 28yrs (18-73yrs);66%(134/202) female;72%(145/202) heterosexual;75%(152/202) UK born. 264 triggers were selected: 27%(55/202) physical/emotional abuse, 81%(164/202) coercive control, and 22%(45/202) sexual abuse. Ten (5%) SUs triggered three DA/V questions, 42(21%) two and 150(74%) one. STI positivity was 4%. 77%(156/202) engaged in high-risk activity. 26%(52/202) had never visited a clinic. Telephonic discussion with the e-service took place in 10%(20/202) SUs: 50%(10/20) received counselling/signposting;10%(2/20) referred to independent DA/V advocate, 30% (6/20) stated historic abuse, 10%(2/20) mistakenly triggered, 5%(1/10) declined support for current abuse and 5%(1/10) disengaged. Of 29%(58/202) SUs who ordered further e-kit(s) 38%(22/58) continued to trigger and 9%(5/58) disclosed sexual assault. Discussion 1.7% SUs reported current DA/V. After attempted contact a supportive DA/V discussion was accepted by 80% SUs. Despite providing online support 38% continued to disclose abuse. Efforts to explore/evaluate safe methods of engaging and supporting DA/V survivors using e-services are required.

IMPACT OF THE CORONAVIRUS (COVID-19) PANDEMIC ON STROKE CODE ACTIVITIES AND OUTCOME: A RETROSPECTIVE OBSERVATIONAL STUDY

Background and aim: The Coronavirus 2019 (COVID-19) pandemic has affected the delivery of healthcare around the world. We assessed the impact of the COVID-19 pandemic on hospital presentations, reperfusion treatment and outcomes in a comprehensive stroke centre. Methods: In this observational study seven months of retrospective data from February 2020 at the beginning of the pandemic were compared to data collected for the same time frame in 2019. Results: There was a transient reduction in stroke presentation only at the beginning of the wave of COVID-19 community transmissions in Sydney. There were significantly more haemorrhagic strokes in the COVID- 19 period (n = 66, 15.4 % vs n = 95, 21.5 %, p = 0.02) and baseline stroke severity was higher (NIHSS median 3 vs 4, p = 0.049). Similar proportions of ischaemic stroke patients received reperfusion therapy in the two time periods (IV thrombolysis [n = 51, 17.3% vs n = 52, 17.9%, p = 0.838];and ECR [n = 38, 12.9% vs n = 46, 15.9%, p = 0.30]). The time from presentation to stroke bed admission was significantly shorter during the COVID-19 period (p = 0.031). Three-month follow-up Modified Rankin Score was 2 (median) in both periods (P = 0.92). Conclusion: There was no change in stroke presentations overall during the 2020 COVID 19 pandemic time period with the exception of the first phase of the pandemic. Baseline stroke severity scores were higher. There was no difference in the degree of disability at three-month follow-up.

Clinical characteristics and outcomes in patients with pneumonia secondary to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2)

Background: Since discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes the disease of COVID-19 has become a global pandemic. Little is known about which risk factors lead to more severe disease or increased mortality in patients diagnosed with SARS-CoV-2. We aimed in this study to compare clinical characteristics associated with disease severity and increased mortality in hospitalized patients with COVID-19. Methods: This was a single-center, retrospective study at The Ohio State University Wexner Medical Center to compare clinical characteristics associated with increased mortality in hospitalized patients with confirmed SARS-CoV-2. Adults patients positive for SARS-CoV-2 between March 1, 2020 and April 20, 2020 were included in the study. Prisoners and pregnant women were excluded. Baseline demographics, clinical characteristics, and outcomes were collected, and then compared to determine association with mortality. Statistical analysis used univariate and multivariate logistic regression analysis to evaluate the relationship between patient characteristics and mortality. Results: The cohort included 92 patients. Median age was 58 years (ranging from 25-93) and 47/92 were men (51%). 12 patients were admitted directly to the intensive care unit (ICU), with 22 additional patients transferred to the ICU. 23 patients required mechanical ventilation. Clinical characteristics significantly associated with mortality in univariate analysis included underlying coronary artery disease (CAD) (OR=7.8, p = 0.002), chronic obstructive pulmonary disease (OR=5.21, p=0.02), living in an extended care facility (ECF) (OR=4.2, p=0.025), and immunocompromised status (OR=4.2, p=0.025). Multivariate analysis showed a statistically significant association in patients with underlying CAD (OR=13.1, p=0.001) and those admitted from an ECF (OR=12.1, p=0.005), when adjusted for other variables in the model. Characteristics Associated with Mortality in Patients with COVID-19 in Univariate Analysis Conclusion: Our study found that CAD and admission from an ECF were associated with SARS-CoV-2 mortality, when adjusted for age and other comorbidities. Further studies are necessary to identify potential preventative strategies to mitigate mortality in this vulnerable population.

Patient satisfaction following implementation of a telephone clinic prior to intrauterine contraception (IUC) fitting

Introduction: During the COVID-19 pandemic remote consultations were implemented to meet patients' sexual & reproductive health needs, and minimise COVID infection risk to patients and staff. Patients requesting IUC were offered a telephonic consultation appointment for a clinical assessment and full counselling about their chosen IUC method. Eligible patients scheduled an IUC fitting and were sent SMS links to IUC video and postal home-sampling service for STI screening. Methods: Patients receiving an IUC fitting between May and July 2020 were invited by SMS to complete a service evaluation through survey monkey No demographic information was recorded. Results: 30 (19%) of 156 women invited completed the questionnaire 20 (67%) were new attendees to the service;28 (93%) rated the service as excellent and 2/30 (7% very good;27 (90%) were very likely to access the phone clinic in the future and 3/30 (10%) likely;30/30 (100%) stated they would recommend the service to friends or family. 27 (90%) found the online video resources helpful, 25 (83%) stated their consultation started on time, 27 (90%) were very satisfied with the waiting time between telephone appointment & fit. 5 (17%) saw the same staff member at both the telephone and IUC fitting appointments. Of those that didnt 25/25 did not report dissatisfaction. 30/30 (100%) were satisfied with access to advice & support after the fitting and 23 (77%) were satisfied using a postal home-sampling service for STI screening prior to the fitting, the remainder were neither satisfied or dissatisfied. Discussion: The COVID-19 pandemic has given us an opportunity to implement creative and remote modalities of SRH delivery. Implementing a telephone counselling clinic prior to IUC fitting showed high levels of acceptability with women and given this feedback will likely continue to be offered post COVID.

Staff feedback following implementation of a telephone clinic for clinical assessment and method counselling prior to Intrauterine contraception fitting

Introduction: An adapted operational pathway was necessary, following the COVID-19 pandemic, to maintain availability to long acting reversible contraception (LARC). Following requests for intrauterine contraception (IUC) patients were allocated a telephone appointment for clinical assessment and full method counselling before being offered fitting appointment. Methods: 156 IUC insertions were undertaken in an eight week period following implementation on May 18th. In July SRH Staff were invited to provide feedback regarding the new model of working via an anonymous survey monkey questionnaire. Results: Twelve (86%) of 14 staff completed the questionnaire: 10 (83%) would definitely support LARC-phone service post COVID-19, the remainder probably would;9 (75%) strongly agreed that LARC-phone should replace face-to-face triage, 3/12 (25%) agreed. In some instances, staff reported phone communication was more difficult than face-to-face;four (33%) reported hard of hearing/deafness, seven (58%) mental health illness, seven (58%) safeguarding issues and three (25%) when talking with those under 18. One had concerns with implementing telephone appointments for all except those meeting locally-defined criteria, other feedback included;talking to patients with a language barrier, ensuring it is safe at home to talk to the patient, restriction of service access for vulnerable groups, loss of opportunistic offer LARC-offer and consistent clear documentation especially when the triage and fit aspect of care were delivered by separate individuals. Discussion: Staff supported this innovation at a time when there were clear benefits for change. Feedback suggests telephone appointments enabled prompt access for many, for those who have difficulty we suggest exploring the utility of video consultation. In current pandemic working where first contact with the service is via phone vulnerable groups should be supported to access face-to-face triage and staff should ensure that all those making contact with sexual health services for any need who are eligible for LARC are offered this method.

The Norwegian football family and strategic crisis communication. (Special Issue: Sport and the coronavirus crisis.)

This commentary uses the Norwegian Football Association's COVID-19 crisis communication strategy as an example of how federations can take an active role and use their influence to guide and be proactive in the opening of a society after a lockdown. By paying close attention to the public debate and by interviewing the federation's communication director, the authors outlined the four phases of the strategic crisis communication-and the consequences of them in Norway. While the first consequence was the postponing of the Euro Qualifier against Serbia on March 26 for the European Championship this summer, the lockdown changed the focus quickly, and the strategy became about getting all players back on the football fields. The authors elaborated on how a major federation can (and maybe should) take a leading role by using its "voice" in the media and public and expertise to aid reopening a society after lockdown.